Prevalence and incidence of rare diseases: Bibilographic data

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1 2 March 2016 Prevalence and incidence of rare diseases: Bibilographic data s listed by decreasing prevalence, incidence or number of published cases

2 Methodology Orphanet carries out a systematic survey of literature in order to estimate the prevalence and incidence of rare diseases. This study aims to collect new data regarding point prevalence, birth prevalence and incidence, and to update already published data according to new scientific studies or other available data. This data is presented in the following reports published biannually: Prevalence, incidence or number of published cases listed by diseases (in alphabetical order) ; s listed by decreasing prevalence, incidence or number of published cases ; Data collection A number of different sources are used : Registries (RARECARE, EUROCAT, etc) ; National/international health institutes and agencies (Institut National de Veille Sanitaire (French Institute of Health Surveillance); American Center of Control and Prevention, American National Cancer Institute, European Medicines Agency, World Health Organization etc) ; Medline is consulted using the following search algorithm : «names» AND Epidemiology[MeSH:NoExp] OR Incidence[Title/abstract] OR Prevalence[Title/ abstract] OR Epidemiology[Title/abstract]; Medical texts, grey literature and reports from experts ; Orphanet collaborating experts. Data characteristics The data published in this document are worldwide estimations, or European estimations if a worldwide estimation is not available. The published data is raw collected data or extrapolations of raw data at worldwide or European level when no genetic founder effect is suspected as a cause of a disease. If a range of national data is available, the average is calculated to estimate the worldwide or European prevalence or incidence. When a range of data sources is available, the most recent data source that meets a certain number of quality criteria is favoured (registries, meta-analyses, population-based studies, large cohorts studies). For congenital diseases, the prevalence is estimated, so that: Prevalence = birth prevalence x (patient life expectancy/general population life expectancy). When only incidence data is documented, the prevalence is estimated when possible, so that : Prevalence = incidence x disease mean duration. When neither prevalence nor incidence data is available, which is the case for very rare diseases, the number of cases or families documented in the medical literature is provided. Limitations of the study The prevalence and incidence data presented in this report are only estimations and cannot be considered to be absolutely correct. The average values presented in this report do not take into account the heterogeneous nature of the methodologies employed by the studies considered in the literature survey. The validity and exactitude of raw data sources is taken for granted and have not been verified. Thus, confusion between terms such as incidence and prevalence and/or birth prevalence is possible due to the interchangeable use of these terms in certain sources. It is possible that prevalence is overestimated in some cases as epidemiological studies are generally based on hospital data in regions with higher prevalence. Data presentation Without specification, published figures are worldwide. An asterisk * indicates European data.. Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March

3 List of diseases or groups of diseases by decreasing prevalence prevalence (/,000) Maculopapular cutaneous mastocytosis BP* 1480 Ventricular septal defect BP* 853 Fetal and neonatal alloimmune thrombocytopenia BP* Posterior meningocele.0 BP* 3388 Neural tube defect BP* Non-functioning pituitary adenoma * 648 Noonan 70.0 BP* Tumor of endocrine glands 64.0 * 2014 Cleft palate 53.6 BP* 535 Cutaneous lupus erythematosus 50.0 * 706 Patent arterial duct 50.0 BP* 8 47,XYY 50.0 BP* 48 Congenital bilateral absence of vas deferens 50.0 * Iniencephaly 50.0 * Pneumonia caused by Pseudomonas aeruginosa infection 50.0 * 93 Renal agenesis, unilateral 50.0 BP Squamous cell carcinoma of head and neck 49.0 * 2185 Congenital hydrocephalus 46.5 BP* Congenital isolated thyroxine-binding globulin 46.0 * Preeclampsia 45.0 * Renal dysplasia 43.5 BP* 3375 Trisomy X 42.5 * 801 Scleroderma Renal cell carcinoma 42.0 * Non-immune hydrops fetalis 42.0 BP 1646 Partial chromosome Y deletion Eosinophilic esophagitis Familial long QT 40.0 BP* 294 Fetal cytomegalovirus 40.0 * Genetic peripheral neuropathy Cardiogenic shock 40.0 * Romano-Ward 40.0 * 3189 Congenital pulmonary valve stenosis 39.3 BP* 442 Congenital hypothyroidism 38.0 BP* Uveitis 38.0 * Moderate and severe traumatic brain injury 37.8 * q11.2 deletion 37.5 BP Primary congenital hypothyroidism 37.5 * Acute sensorineural hearing loss by acute acoustic trauma or sudden deafness or surgery induced acoustic trauma 37.0 * Non-papillary transitional cell carcinoma of the bladder 37.0 * 545 Follicular lymphoma 36.0 * Solar urticaria 36.0 * prevalence (/,000) 1457 Aorta coarctation 35.6 BP* 2764 Osteochondritis dissecans 35.0 * 1048 Isolated anencephaly/exencephaly 35.0 BP* Radiation proctitis 35.0 * Uremic pruritus 35.0 * 3303 Tetralogy of Fallot 34.0 BP 636 Neurofibromatosis type BP Permanent congenital hypothyroidism 33.3 BP* 858 Congenital toxoplasmosis 33.0 BP* Placental insufficiency Fragile X Vernal keratoconjunctivitis 32.0 * Sepsis in premature infants 32.0 * Spinal cord injury 32.0 * Transposition of the great arteries 31.7 BP* 2140 Congenital diaphragmatic hernia 30.0 BP 563 Peripartum cardiomyopathy 30.0 BP 1330 Partial atrioventricular canal 30.0 * 729 Polycythemia vera 30.0 * Ovarian cancer 30.0 * 301 Wild type ATTR amyloidosis 30.0 * Non-acquired combined pituitary hormone BP* Central retinal vein occlusion 28.0 * 1656 Dermatitis herpetiformis 27.0 * B-cell chronic lymphocytic leukemia 27.0 * 791 Retinitis pigmentosa Posttransplant lymphoproliferative disease 26.2 * Thrombotic thrombocytopenic purpura 25.5 * Cytomegalovirus disease in patients with impaired cell mediated immunity deemed at 25.5 * risk 166 Charcot-Marie-Tooth disease 25.0 * 2 Immune thrombocytopenic purpura 25.0 * 701 Alopecia universalis 25.0 * 145 Hereditary breast and ovarian cancer 25.0 * 2073 Narcolepsy-cataplexy 25.0 * Thyroid hemiagenesis Syndactyly type BP* Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March

4 94058 Neovascular glaucoma 24.4 * prevalence (/,000) 1199 Esophageal atresia 24.3 BP* 1531 Craniosynostosis 24.3 BP* Congenitally uncorrected transposition of the BP* great arteries 2248 Hypoplastic left heart 24.0 BP Primary cutaneous T-cell lymphoma 24.0 * 2368 Gastroschisis 23.7 BP* 3394 Soft tissue sarcoma 23.7 * 2137 Chronic autoimmune hepatitis Multicystic dysplastic kidney BP Unilateral multicystic dysplastic kidney 23.2 BP Anal fistula 23.0 * Scarring in glaucoma filtration surgical procedures 22.0 * Pouchitis 22.0 * Pulmonary fungal infections in patients deemed at risk 22.0 * 636 Neurofibromatosis type * Congenital hypothyroidism due to developmental anomaly 21.3 * 186 Primary biliary cirrhosis Oligoarticular juvenile arthritis 20.5 * 60 Alpha-1-antitrypsin 20.0 * 70 Proximal spinal muscular atrophy 20.0 BP* 3389 Tuberculosis 20.0 * 1329 Complete atrioventricular canal 20.0 BP* 557 Isolated anorectal malformation 20.0 BP 130 Brugada 20.0 * Congenital sucrase-isomaltase 20.0 * 1330 Partial atrioventricular canal 20.0 BP* 247 Arrhythmogenic right ventricular cardiomyopathy Infant acute respiratory distress 20.0 * Acute liver failure 20.0 * AIDS wasting 20.0 * Proximal 16p11.2 microdeletion 20.0 * 823 Isolated spina bifida 18.6 BP* Biliary atresia 18.5 BP 704 Pemphigus vulgaris 18.0 * Non-infectious posterior uveitis 18.0 * 154 Familial isolated dilated cardiomyopathy 17.5 * Charcot-Marie-Tooth disease type Trisomy BP 2032 Idiopathic pulmonary fibrosis Primary lymphedema 16.7 * 461 Recessive X-linked ichthyosis 16.6 * 774 Hereditary hemorrhagic telangiectasia 16.0 * prevalence (/,000) 1201 Atresia of small intestine 16.0 BP* Buerger disease Diffuse large B-cell lymphoma 16.0 * Primary membranoproliferative glomerulonephritis 16.0 * Acute peripheral arterial occlusion 16.0 * Stromal keratitis 16.0 * Microtia 15.5 BP Systemic sclerosis 15.4 * Duchenne muscular dystrophy 15.1 BP* 558 Marfan Sickle cell anemia 15.0 * 2382 Lennox-Gastaut 15.0 * 2828 Young-onset Parkinson disease 15.0 * Hepatocellular carcinoma 15.0 * Neuroleptic malignant 15.0 * Familial cerebral cavernous malformation Atopic keratoconjunctivitis 15.0 * Dentinogenesis imperfecta type * Dentinogenesis imperfecta 14.5 * Thyroid ectopia 14.3 * 214 Cystinuria Chronic primary adrenal insufficiency 14.0 * 2162 Holoprosencephaly 13.4 BP* 3193 Supravalvular aortic stenosis 13.3 * Gastrointestinal stromal tumor 13.0 * Bronchopulmonary dysplasia 13.0 * Mucolipidosis type III alpha/beta Thyroid carcinoma Triploidy 12.6 BP* 273 Steinert myotonic dystrophy Sarcoidosis Ehlers-Danlos, hypermobility type 12.5 * 903 Von Willebrand disease Lymphatic malformation 12.5 * Addison disease 12.5 * Medium chain acyl-coa dehydrogenase BP* Chronic pain requiring intraspinal analgesia 12.0 * Multiple myeloma 11.9 * 660 Omphalocele 11.7 BP* 1866 Focal, segmental or multifocal dystonia 11.7 * Hemophilia A BP Small cell lung cancer 11.2 * 635 Neuroblastoma 11.0 * Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March

5 prevalence (/,000) 3109 Mayer-Rokitansky-Küster-Hauser 11.0 BP 890 Hepatic veno-occlusive disease 11.0 * AL amyloidosis 11.0 * 388 Hirschsprung disease 10.9 BP* 904 Williams 10.8 BP 700 Alopecia totalis 10.5 * 827 Stargardt disease 10.0 * 1146 Digitotalar dysmorphism Linear nevus sebaceus 10.0 BP* 716 Phenylketonuria 10.0 BP* 418 Congenital adrenal hyperplasia 10.0 * 805 Tuberous sclerosis complex 10.0 BP* 654 Nephroblastoma 10.0 BP* 569 Familial or sporadic hemiplegic migraine 10.0 * 233 Duane retraction 10.0 * 3157 Septo-optic dysplasia spectrum 10.0 BP* 412 Hyperlipoproteinemia type Hypereosinophilic of undetermined significance 10.0 * 3286 Catecholaminergic polymorphic ventricular tachycardia 10.0 * Dermatofibrosarcoma protuberans 10.0 * Recurrent acute pancreatitis 10.0 * Acquired aneurysmal subarachnoid hemorrhage 10.0 * Partial deep dermal and full thickness burns 10.0 * Polymalformative genetic with increased risk of developing cancer 10.0 * Glial tumor 10.0 * 1114 Aplasia cutis congenita 10.0 BP Carcinoma of esophagus Bone sarcoma 9.29 * Gardner 9.1 BP 2443 Mitochondrial oxidative phosphorylation disorder due to nuclear DNA anomalies 9.0 * 900 Granulomatosis with polyangiitis 9.0 * 1203 Duodenal atresia 9.0 * 1203 Duodenal atresia 9.0 BP* Mastocytosis 9.0 * Congenital total pulmonary venous return anomaly 9.0 BP Choanal atresia 8.6 BP* Apnea of prematurity 8.5 * 3280 Syringomyelia 8.4 * Anophthalmia - microphthalmia 8.3 BP* 2444 Congenital pulmonary airway malformation 8.2 BP* 171 Primary sclerosing cholangitis Mucopolysaccharidosis type * 930 Idiopathic achalasia West 8.0 * prevalence (/,000) 194 Ocular coloboma 8.0 BP* CREST 8.0 * Juvenile rheumatoid factor-negative polyarthritis 8.0 * Congenital heart malformation 7.8 BP* 589 Myasthenia gravis Hemophilia 7.7 * Sporadic adult-onset ataxia of unknown * etiology 72 Angelman Osteogenesis imperfecta 7.5 * 4 Laryngo-tracheo-esophageal cleft 7.5 BP* 1464 Univentricular heart 7.5 BP Classic congenital adrenal hyperplasia due to hydroxylase, salt wasting form 7.5 * Classic congenital adrenal hyperplasia due to BP* 21-hydroxylase, salt wasting form 586 Cystic fibrosis 7.4 * 821 Sotos 7.1 BP 732 Polymyositis 7.1 * 705 Pendred 7.0 * 1332 Medullary thyroid carcinoma 7.0 * Classic congenital adrenal hyperplasia due to BP 21-hydroxylase Classic congenital adrenal hyperplasia due to * 21-hydroxylase Recurrent hepatitis C virus induced liver disease in liver transplant recipients 7.0 * Primary progressive aphasia p13.11 microdeletion 7.0 BP 2059 Fryns 7.0 BP* 42 Medium chain acyl-coa dehydrogenase Mucopolysaccharidosis type * 418 Congenital adrenal hyperplasia 6.7 BP* 3366 Isolated trigonocephaly 6.7 BP* SUNCT 6.7 * Hypohidrotic ectodermal dysplasia 6.7 * Myotonic dystrophy Iminoglycinuria 6.68 * Iminoglycinuria 6.67 BP* Cat-scratch disease 6.6 * 138 CHARGE 6.5 BP 553 Cushing 6.5 * Vasculitis 6.3 * Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March

6 prevalence (/,000) 887 VACTERL/VATER association 6.25 BP* q21.31 microdeletion 6.25 * 733 Familial adenomatous polyposis 6.0 * 790 Retinoblastoma 6.0 BP 221 Dermatomyositis 6.0 * 683 Progressive supranuclear palsy Chronic myeloid leukemia 6.0 * 609 Tibial muscular dystrophy 6.0 * Cerebral arteriovenous malformation 6.0 * Benign schwannoma 6.0 * 524 Li-Fraumeni Oculocutaneous albinism Neuroblastoma 5.8 BP* 1037 Arthrogryposis multiplex congenita 5.7 BP* Enthesitis-related arthritis 5.7 * 881 Turner 5.5 BP* 963 Acromegaly Split hand-split foot malformation 5.4 BP* 2542 Isolated anophthalmia - microphthalmia 5.3 BP* 738 Porphyria Rett 5.0 BP* 792 X-linked retinoschisis Hereditary fructose intolerance 5.0 * 718 Isolated Pierre Robin 5.0 BP* 287 Ehlers-Danlos, classic type Primary ciliary dyskinesia 5.0 BP* 685 Hereditary spastic paraplegia 5.0 * 43 X-linked adrenoleukodystrophy 5.0 BP 251 Multiple epiphyseal dysplasia 5.0 * Ehlers-Danlos type * Systemic-onset juvenile idiopathic arthritis 5.0 * Calciphylaxis 5.0 * Hemophilia A Usher 4.8 * Tritanopia 4.8 * Duchenne muscular dystrophy Congenital heart block 4.54 BP 269 Facioscapulohumeral dystrophy 4.5 * Wild type ABeta2M amyloidosis 4.5 * 175 Cartilage-hair hypoplasia 4.34 BP* 104 Leber hereditary optic neuropathy Neurogenic arthrogryposis multiplex congenita 4.3 BP* 3384 Truncus arteriosus 4.3 BP 2116 Hartnup disease 4.2 prevalence (/,000) 1209 Tricuspid atresia 4.2 BP* Juvenile rheumatoid factor-positive polyarthritis 4.2 * Juvenile psoriatic arthritis 4.2 * 2130 Hemimelia 4.15 * Posterior urethral valve BP* 778 Rett 4.0 * 15 Achondroplasia 4.0 BP 564 Meckel 4.0 BP 819 Smith-Magenis Tetrasomy 12p 4.0 BP* 1928 Congenital lobar emphysema 4.0 BP 3193 Supravalvular aortic stenosis 4.0 BP* MALT lymphoma 4.0 * Cutaneous neuroendocrine carcinoma 4.0 * Koolen-De Vries 4.0 * Cushing disease 4.0 * Familial thyroid dyshormonogenesis 4.0 * Porphyria cutanea tarda 4.0 * Spastic paraplegia type * Central diabetes insipidus 4.0 * p inverted duplication/deletion 3.9 BP* 803 Amyotrophic lateral sclerosis Acute interstitial pneumonia 3.8 * Indolent systemic mastocytosis 3.8 * 2467 Systemic mastocytosis Kallmann 3.75 * 3378 Trisomy BP* 3451 West 3.7 BP 2932 Chronic inflammatory demyelinating polyneuropathy 3.7 * 3465 Worster-Drought 3.7 * 818 Smith-Lemli-Opitz 3.7 BP* Enlarged parietal foramina Congenital glaucoma 3.6 BP* 640 Hereditary neuropathy with liability to pressure palsies 3.5 * 1880 Ebstein malformation 3.5 BP* 2655 Thanatophoric dysplasia 3.5 BP* 3205 Sturge-Weber 3.5 BP* 2103 Guillain-Barré 3.5 * 81 Antisynthetase Multiple system atrophy Mantle cell lymphoma 3.5 * Athyreosis 3.5 * Thyroid hypoplasia 3.5 Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March

7 Rare carcinoma of pancreas Short bowel 3.4 * 218 Darier disease 3.4 * 652 Multiple endocrine neoplasia type * 905 Wilson disease Hypochondroplasia 3.3 * 1172 Autosomal recessive cerebellar ataxia Autosomal dominant optic atrophy 3.3 prevalence (/,000) Hypoplastic right heart 3.3 BP* Pulmonary arterial hypertension 3.3 * 926 Acatalasemia 3.2 * 158 Systemic primary carnitine 3.2 BP* 075 Gastric endocrine tumor 3.2 * 2322 Kabuki 3.1 * Pleural mesothelioma 3.1 * Acute inflammatory demyelinating polyradiculoneuropathy 3.1 * Bladder exstrophy 3.05 BP 673 Malaria 3.0 * 794 Saethre-Chotzen 3.0 BP* 136 CADASIL 3.0 * 282 Frontotemporal dementia 3.0 * 767 Polyarteritis nodosa 3.0 * 2745 Opitz G/BBB 3.0 * Bacterial toxic-shock Myelofibrosis with myeloid metaplasia 3.0 * Chronic thromboembolic pulmonary hypertension 3.0 * Congenitally corrected transposition of the great arteries 3.0 BP Ileal pouch anal anastomosis related faecal incontinence 3.0 * Limbal stem cell 3.0 * 653 Multiple endocrine neoplasia type * 739 Prader-Willi 2.8 BP* 374 Goldenhar 2.8 BP* 506 Leigh 2.8 BP* Severe hemophilia A 2.8 * 626 Large congenital melanocytic nevus 2.75 * 399 Huntington disease Autosomal dominant cerebellar ataxia Achromatopsia methylcrotonyl-CoA carboxylase 2.65 BP* Oculocutaneous albinism type Gitelman 2.5 * 1034 Amniotic bands 2.5 BP* 1872 Cone rod dystrophy 2.5 * ,XX ovotesticular disorder of sex development 2.5 BP 2337 Non-epidermolytic palmoplantar keratoderma 2.5 * 65 Leber congenital amaurosis 2.5 BP 758 Pseudoxanthoma elasticum 2.5 * 94 Astrocytoma 2.5 * ,XX testicular disorder of sex development Dravet 2.5 BP Familial isolated restrictive cardiomyopathy 2.5 * Peripheral resistance to thyroid hormones 2.5 * Dense deposit disease Progressive non-fluent aphasia 2.5 * Classic congenital adrenal hyperplasia due to hydroxylase, simple virilizing 2.5 * form 65 Leber congenital amaurosis Oculocutaneous albinism type Meconium aspiration 2.44 * prevalence (/,000) Epispadias 2.4 BP* Multiple system atrophy, parkinsonian type 2.4 * 116 Beckwith-Wiedemann 2.3 BP* Graft versus host disease 2.3 * 315 Lead poisoning 2.3 * 905 Wilson disease 2.2 BP 2869 Peutz-Jeghers 2.2 BP 304 Epidermolysis bullosa simplex 2.2 BP* Legius 2.2 BP Becker muscular dystrophy 2.2 BP* 217 Isolated Dandy-Walker malformation 2.1 * Cholangiocarcinoma Friedreich ataxia 2.0 * 480 Kearns-Sayre 2.0 * 607 Nemaline myopathy 2.0 BP* 280 Wolf-Hirschhorn 2.0 BP* 126 Blepharophimosis - epicanthus inversus - ptosis Treacher-Collins 2.0 BP* 352 Galactosemia 2.0 BP* 3346 Tracheal agenesis 2.0 BP* 63 Alport 2.0 * 3129 Sarcosinemia 2.0 BP 1699 Trisomy 12p 2.0 BP 2017 Sternal cleft 2.0 BP* 185 Scimitar 2.0 BP* Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March

8 2345 Isolated Klippel-Feil 2.0 * Craniopharyngioma 2.0 * Fibular hemimelia 2.0 * Anaplastic large cell lymphoma 2.0 * fluorouracil poisoning 2.0 * Paroxysmal hemicrania 2.0 * Childhood disintegrative disorder 2.0 * 657 Congenital isolated hyperinsulinism 2.0 BP Posterior urethral valve 2.0 * Ring chromosome 2.0 BP 199 Cornelia de Lange 1.9 * prevalence (/,000) 10 48,XXYY 1.9 BP* Inherited epidermolysis bullosa 1.9 BP* Malignant sex cord stromal tumor of ovary 1.85 * 304 Epidermolysis bullosa simplex Annular pancreas 1.8 BP* Muenke 1.8 BP* 664 Ornithine transcarbamylase 1.77 BP 77 Aniridia p23.1 microduplication Hydrocephalus with stenosis of the aqueduct 1.7 BP of Sylvius 2182 Hydrocephalus with stenosis of the aqueduct 1.7 of Sylvius 637 Neurofibromatosis type * 2152 Mowat-Wilson 1.7 BP* 1848 Renal agenesis, bilateral 1.7 BP* Hemophilia B 1.7 * 394 Classic homocystinuria 1.65 * 899 Walker-Warburg 1.65 BP* Severe combined immuno 1.65 BP* 1915 Fetal alcohol 1.6 BP* X-linked Charcot-Marie-Tooth disease 1.6 * Biotinidase 1.6 * Biotinidase 1.6 BP Becker muscular dystrophy Coffin-Lowry Budd-Chiari 1.5 * 180 Choroideremia 1.5 * 2019 Femur-fibula-ulna complex 1.5 BP* 389 Langerhans cell histiocytosis 1.5 * 137 Congenital disorder of glycosylation 1.5 BP* Primary lateral sclerosis 1.5 * 641 Multifocal motor neuropathy Neuromyelitis optica 1.5 * Incessant infant ventricular tachycardia 1.5 BP* prevalence (/,000) Idiopathic neonatal atrial flutter 1.5 BP* Intestinal epithelial dysplasia 1.5 BP* Spinocerebellar ataxia type Spinocerebellar ataxia type Spinocerebellar ataxia type Malignant peritoneal mesothelioma 1.5 * Hypereosinophilic 1.5 * 183 Eosinophilic granulomatosis with polyangiitis Metachromatic leukodystrophy 1.47 BP* Sanfilippo type A 1.4 BP 195 Cat-eye 1.35 BP* Citrullinemia type I 1.35 * 355 Gaucher disease 1.3 BP Oculocutaneous albinism type 1B Oculocutaneous albinism type 1A Syndromic X-linked ichthyosis 1.3 * 1880 Ebstein malformation 1.25 * 2481 Neurocutaneous melanocytosis 1.25 * 628 Diastrophic dwarfism 1.2 * 2750 Orofaciodigital type BP* Superficial pemphigus 1.2 * Autosomal recessive polycystic kidney * disease Nevus of Ito 1.17 * 72 Angelman 1.1 BP* 289 Ellis Van Creveld 1.1 BP 2911 Poland 1.1 BP* 224 Neonatal diabetes mellitus 1.1 BP* Joubert and related disorders 1.1 BP Idiopathic pulmonary arterial hypertension 1.1 * 377 Gorlin Krabbe disease 1.0 * 614 Thomsen and Becker disease Blue cone monochromatism Blue cone monochromatism 1.0 BP 681 Hypokalemic periodic paralysis 1.0 * 53 Albers-Schönberg osteopetrosis Cornelia de Lange 1.0 BP* 370 Glycogen storage disease due to phosphorylase kinase 1.0 BP* 217 Isolated Dandy-Walker malformation 1.0 BP* 33 Isovaleric acidemia 1.0 * 2308 Jacobsen 1.0 BP* 606 Proximal myotonic myopathy 1.0 * 355 Gaucher disease 1.0 * Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March

9 364 Glycogen storage disease due to glucose-6- phosphatase 1.0 BP 646 Niemann-Pick disease type C 1.0 * 2134 Atypical hemolytic-uremic 1.0 * 267 Autosomal recessive limb-girdle muscular dystrophy type 2A 1.0 * 1552 Currarino triad 1.0 * 189 Hidrotic ectodermal dysplasia 1.0 * prevalence (/,000) 254 Spondylometaphyseal dysplasia 1.0 BP* 2578 Mayer-Rokitansky-Küster-Hauser type BP* 296 Enchondromatosis 1.0 * 647 Nijmegen breakage 1.0 BP 2924 Isolated polycystic liver disease 1.0 * Idiopathic and/or familial pulmonary arterial * hypertension 3403 Uhl anomaly 1.0 BP 3449 Weill-Marchesani Medulloblastoma 1.0 * 360 Glioblastoma Ehlers-Danlos, kyphoscoliotic type 1.0 BP 286 Ehlers-Danlos, vascular type 1.0 * 531 Miller-Dieker 1.0 BP* 396 Chronic hiccup 1.0 * 5 Long chain 3-hydroxyacyl-CoA dehydrogenase 1.0 BP* 25 Glutaryl-CoA dehydrogenase 1.0 BP 177 Rhizomelic chondrodysplasia punctata 1.0 * Autosomal recessive limb-girdle muscular dystrophy type 2I 1.0 * Acanthamoeba keratitis 1.0 * Cobblestone lissencephaly 1.0 BP* Oculocutaneous albinism type Glycogen storage disease due to glucose phosphatase type a 1.0 BP* Gaucher disease type * Hereditary angioedema 1.0 * Diffuse alveolar hemorrhage 1.0 * X-linked Emery-Dreifuss muscular dystrophy X-linked Emery-Dreifuss muscular dystrophy 1.0 BP ,XXXY 1.0 BP* Congenital hypothyroidism due to transplacental passage of maternal TSHbinding inhibitory antibodies 1.0 * Spondyloepiphyseal dysplasia congenita 1.0 BP* Localized Castleman disease Dentin dysplasia type I 1.0 * Febrile infection-related epilepsy 1.0 * prevalence (/,000) Malignant tumor of fallopian tubes 1.0 * Glycogen storage disease due to liver phosphorylase kinase 1.0 BP* 141 Canavan disease 1.0 BP 577 Mucolipidosis type III 1.0 BP* Familial chylomicronemia 1.0 * Waldenström macroglobulinemia 1.0 * Mal de Meleda Sirenomelia 0.98 BP Autosomal erythropoietic protoporphyria 0.92 * 207 Crouzon disease 0.9 BP* 2131 Alternating hemiplegia of childhood 0.9 BP* 882 Tyrosinemia type BP Lewis-Sumner 0.9 * 581 Mucopolysaccharidosis type BP* 576 Mucolipidosis type II 0.84 BP* Complete androgen insensitivity Mucopolysaccharidosis type BP Glycogen storage disease due to acid maltase BP* 2346 Angioosteohypertrophic 0.8 BP* 813 Silver-Russell 0.8 BP* 1461 Criss-cross heart 0.8 BP* Inherited epidermolysis bullosa 0.8 * Severe hemophilia B 0.8 * 3312 Thalidomide embryopathy Cystinosis 0.75 BP 181 X-linked hypohidrotic ectodermal dysplasia 0.75 BP* 354 GM1 gangliosidosis 0.75 BP* 667 Autosomal recessive malignant osteopetrosis 0.75 BP* 1501 Adrenocortical carcinoma 0.75 * Congenital adrenal hyperplasia due to beta-hydroxylase 0.75 BP* Congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase 0.75 BP* 487 Krabbe disease 0.7 BP 464 Incontinentia pigmenti 0.7 BP* 392 Holt-Oram 0.7 BP* 726 Alpers-Huttenlocher 0.7 BP* 110 Bardet-Biedl 0.7 * 303 Dystrophic epidermolysis bullosa Osteogenesis imperfecta type BP* Hurler 0.7 BP* 580 Mucopolysaccharidosis type BP 796 Sandhoff disease 0.67 BP* 124 Blackfan-Diamond anemia 0.67 BP* Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March

10 prevalence (/,000) 511 Maple syrup urine disease 0.67 BP 2591 Infantile myofibromatosis 0.67 BP* 3282 Multifocal atrial tachycardia 0.67 BP 1335 Pentalogy of Cantrell 0.67 BP Hematopoietic stem cell transplantation 0.65 * 84 Fanconi anemia 0.62 BP* 783 Rubinstein-Taybi 0.6 BP* 474 Jeune 0.6 BP* 3287 Takayasu arteritis 0.6 * 994 Fetal akinesia deformation sequence 0.6 BP* 2345 Isolated Klippel-Feil 0.6 BP* Disorder of bile acid synthesis 0.6 * Sympathetic ophthalmia 0.6 * Paroxysmal kinesigenic dyskinesia 0.6 Progressive supranuclear palsy - corticobasal * Juvenile Huntington disease 0.6 * Moderately severe hemophilia B 0.6 * Mild hemophilia B 0.6 * 54 X-linked recessive ocular albinism 0.58 BP* Pulmonary arterial hypertension associated * with congenital heart disease 562 McCune-Albright 0.55 * 313 Lamellar ichthyosis 0.55 * ,XXXXY 0.55 BP* Acute intermittent porphyria 0.54 * Cloacal exstrophy 0.54 BP 682 Hyperkalemic periodic paralysis 0.5 * 23 Argininosuccinic aciduria 0.5 * 255 Dopa-responsive dystonia Inclusion body myositis 0.5 * 828 Stickler 0.5 BP* 634 Netherton 0.5 BP* 634 Netherton 0.5 * 902 Werner 0.5 * 3427 Double outlet left ventricle 0.5 BP 811 Shwachman-Diamond 0.5 BP 747 Autoimmune pulmonary alveolar proteinosis Axenfeld-Rieger 0.5 * Combined of factor V and factor * VIII 122 Birt-Hogg-Dubé 0.5 * Pleuropulmonary blastoma 0.5 BP* Sanfilippo type A 0.5 * Holocarboxylase synthetase 0.5 BP* Ehlers-Danlos 0.5 BP* Autosomal recessive congenital ichthyosis 0.5 * Hurler 0.5 * 201 Cowden 0.5 * prevalence (/,000) Ataxia-telangiectasia 0.49 * Congenital adrenal hyperplasia due to * beta-hydroxylase 379 Chronic granulomatous disease 0.46 BP 23 Argininosuccinic aciduria 0.46 BP 676 Hereditary chronic pancreatitis 0.43 * 52 Alagille 0.4 BP* 2869 Peutz-Jeghers 0.4 * 1452 Cleidocranial dysplasia 0.4 BP* 915 Aarskog-Scott 0.4 BP* 1215 Autosomal dominant optic atrophy plus 0.4 * 2315 Johanson-Blizzard 0.4 BP* 8 Pyruvate carboxylase 0.4 BP* 256 Early-onset generalized limb-onset dystonia 0.4 * 503 Autosomal dominant Larsen 0.4 BP* Severe congenital neutropenia 0.4 BP* 88 Idiopathic aplastic anemia 0.4 * Niemann-Pick disease type B 0.4 * Mucopolysaccharidosis type 2, severe form 0.4 BP* Non-acquired isolated growth hormone Permanent neonatal diabetes mellitus 0.38 BP* 3440 Waardenburg 0.37 BP* 290 Congenital rubella 0.35 BP* Lambert-Eaton myasthenic Lesch-Nyhan 0.34 BP* 96 Ataxia with vitamin E 0.33 * 565 Menkes disease 0.33 BP* 327 Congenital factor VII 0.33 * 140 Campomelic dysplasia 0.33 BP* Aggressive systemic mastocytosis 0.33 * Porphyria variegata 0.32 * 147 Carbamoyl-phosphate synthetase Emery-Dreifuss muscular dystrophy 0.3 * 394 Classic homocystinuria 0.3 BP 258 Congenital muscular dystrophy type 1A 0.3 * 84 Fanconi anemia Autosomal dominant popliteal pterygium Mirror polydactyly - vertebral segmentation * limbs defects 633 Laron 0.3 * Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March

11 prevalence (/,000) 2299 Aortic arch interruption 0.3 BP* 277 Severe combined immuno due to adenosine deaminase 0.3 BP* 590 Congenital myasthenic 0.3 * 219 Autosomal recessive limb-girdle muscular dystrophy type 2F 0.3 * Transmissible spongiform encephalopathy 0.3 * Congenital non-bullous ichthyosiform erythroderma 0.3 * Jervell and Lange-Nielsen Anthracycline extravasations 0.3 * Isolated agammaglobulinemia MYH9-related disease 0.3 * Popliteal pterygium 0.3 * Chronic recurrent multifocal osteomyelitis Transient neonatal diabetes mellitus 0.3 BP* 845 Tay-Sachs disease 0.28 BP 811 Shwachman-Diamond Cockayne 0.27 BP* 702 Pelizaeus-Merzbacher disease 0.25 * 528 Berardinelli-Seip congenital lipodystrophy 0.25 * 678 Papillon-Lefèvre 0.25 X-linked dominant chondrodysplasia punctata 0.25 BP* Niemann-Pick disease type A 0.25 BP* Pulmonary arterial hypertension associated with connective tissue disease 0.25 * 910 Xeroderma pigmentosum 0.23 BP* 324 Fabry disease 0.22 BP* 47 X-linked agammaglobulinemia Barth 0.22 * 436 Hypophosphatasia 0.21 BP* 447 Paroxysmal nocturnal hemoglobinuria 0.2 * 534 Oculocerebrorenal of Lowe WAGR 0.2 BP 385 Neurodegeneration with brain iron accumulation 0.2 * 235 Dubowitz 0.2 BP* 3320 Thrombocytopenia - absent radius 0.2 BP* 6 Pyridoxine-dependent epilepsy 0.2 BP* 2052 Fraser 0.2 BP* 110 Bardet-Biedl 0.2 BP* 277 Severe combined immuno due to adenosine deaminase 0.2 * 35 Propionic acidemia 0.2 * 353 Autosomal recessive limb-girdle muscular dystrophy type 2C 0.2 * prevalence (/,000) Hypohidrotic ectodermal dysplasia with immuno 0.2 BP* Primary hyperoxaluria type * Letterer-Siwe disease 0.2 * Hyperphenylalaninemia Infant botulism 0.2 BP* Extraskeletal myxoid chondrosarcoma 0.2 * 1361 Carnosinemia 0.2 BP 1456 Atypical coarctation of aorta 0.17 BP* 407 Glycine encephalopathy 0.17 * Junctional epidermolysis bullosa, Herlitz type 0.17 BP Pelizaeus-Merzbacher disease, classic form 0.17 * 583 Mucopolysaccharidosis type BP* 85 Congenital dyserythropoietic anemia 0.16 BP* 335 Congenital fibrinogen 0.15 * 538 Lymphangioleiomyomatosis Nephrogenic diabetes insipidus 0.15 * Hermansky-Pudlak 0.15 Pantothenate kinase-associated neurodegeneration 0.15 * 118 Beta-mannosidosis 0.14 BP* 763 Pycnodysostosis Wolfram Agammaglobulinemia 0.13 * 1308 C 0.11 * Autosomal dominant medullary cystic kidney * disease with or without hyperuricemia 61 Alpha-mannosidosis 0.1 * 367 Glycogen storage disease due to glycogen branching enzyme 0.1 BP 512 Metachromatic leukodystrophy 0.1 * 906 Wiskott-Aldrich 0.1 * 628 Diastrophic dwarfism 0.1 BP* 205 Crigler-Najjar 0.1 BP* 773 Refsum disease 0.1 * 1452 Cleidocranial dysplasia Dyskeratosis congenita 0.1 * 204 Creutzfeldt-Jakob disease 0.1 * 1959 Evans 0.1 * 3198 Stiff person and related disorders 0.1 * 326 Congenital factor V 0.1 * 507 Leishmaniasis 0.1 * 3329 Tibial aplasia - ectrodactyly 0.1 * 329 Congenital factor XI 0.1 * 2686 Cyclic neutropenia 0.1 * 298 Mitochondrial neurogastrointestinal encephalomyopathy 0.1 * Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March

12 225 Maternally-inherited diabetes and deafness 0.1 * prevalence (/,000) 209 Cutis laxa 0.1 BP* Colchicine poisoning 0.1 * 119 Autosomal recessive limb-girdle muscular dystrophy type 2E 0.1 * 142 Anaplastic thyroid carcinoma 0.1 * Acquired hemophilia 0.1 * Congenital adrenal hyperplasia due to alpha-hydroxylase 0.1 * Crouzon - acanthosis nigricans 0.1 BP Tibial hemimelia 0.1 BP* Juvenile myelomonocytic leukemia 0.1 * Paroxysmal non-kinesigenic dyskinesia Leukocyte adhesion type I 0.1 * Inhalational anthrax 0.1 * Adult-onset proximal spinal muscular * atrophy, autosomal dominant Mitochondrial membrane protein-associated neurodegeneration Homozygous familial hypercholesterolemia Melorheostosis 0.09 * Aceruloplasminemia Sanfilippo type B 0.09 * Cushing due to macronodular adrenal hyperplasia 0.08 * Heritable pulmonary arterial hypertension 0.08 * 726 Alpers-Huttenlocher 0.07 * Severe congenital neutropenia 0.07 Neonatal acute respiratory distress due to SP-B BP 337 Fibrodysplasia ossificans progressiva X-linked lymphoproliferative disease 0.05 * 2788 Osteoporosis - pseudoglioma 0.05 * 325 Congenital factor II 0.05 * 331 Congenital factor XIII 0.05 * Gaucher disease type * Sialidosis 0.05 BP* Leber plus disease 0.04 * Primary pigmented nodular adrenocortical * disease Naegeli-Franceschetti-Jadassohn * Congenital muscular dystrophy with integrin * alpha Pelizaeus-Merzbacher disease, connatal form 0.03 * Pelizaeus-Merzbacher disease, transitional * form Anotia BP* 740 Hutchinson-Gilford progeria BP prevalence (/,000) 227 Diphallia 0.02 BP 584 Mucopolysaccharidosis type * 3169 Sirenomelia Gaucher disease type * Klippel-Trénaunay * 740 Hutchinson-Gilford progeria Poliomyelitis in patients with 309 immunodeficiencies deemed at risk 8.0E-4 * Frontorhiny 0.0 Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March

13 List of diseases or groups of diseases by decreasing incidence Intrahepatic cholestasis of pregnancy 0.0* Transient congenital hypothyroidism 0.0* Dengue fever Neuroleptic malignant Adult heart tumor 140.9* 3389 Tuberculosis Malaria Squamous cell carcinoma of stomach Perineural cyst 50.0* 558 Marfan 25.0* 2810 Idiopathic facial palsy Leishmaniasis Acute lung injury 25.0* Lyme disease Rare epithelial tumor of stomach 18.6* Uveitis 17.0* 813 Silver-Russell 15.5* 461 Recessive X-linked ichthyosis 15.0* 418 Congenital adrenal hyperplasia 13.35* Complication in hemodialysis 13.0* Carcinoma of gallbladder and extrahepatic biliary tract Non-Hodgkin lymphoma 11.6* 1546 Cryptococcosis 11.0* 435 Ito hypomelanosis 10.85* Lemierre 10.0* 2209 Maternal phenylketonuria 10.0* 3467 Hereditary xanthinuria 9.05* Squamous cell carcinoma of head and neck Astrocytoma 8.0* 1941 Juvenile absence epilepsy 7.5* Carcinoma of esophagus Immune thrombocytopenic purpura 6.75* 448 Hemophilia 6.25* Multiple myeloma Microscopic colitis 6.0* Interstitial lung disease 5.4* 146 Differentiated thyroid carcinoma Primary cutaneous T-cell lymphoma 5.2* Squamous cell carcinoma of esophagus 5.2 incidence(/,000) 3099 Rheumatic fever 5.0* Cholangiocarcinoma Rare carcinoma of pancreas Juvenile polyposis 3.85* 2032 Idiopathic pulmonary fibrosis 3.81* Tumor of endocrine glands 3.75* 548 Leprosy 3.7 Infant acute respiratory distress * Collagenous colitis Thyroid tumor Tumor of testis and paratestis 3.15* 088 Thyroid carcinoma Primary biliary cirrhosis Glioblastoma Mosaic trisomy 8 3.0* Typhoid 3.0* Complete androgen insensitivity * Familial isolated dilated 154 cardiomyopathy 2.91* 513 Acute lymphoblastic leukemia 2.75* Familial thyroid dyshormonogenesis Proximal spinal muscular atrophy 2.6* 877 Endocrine tumor 2.53* 2038 Pulmonary arteriovenous fistula Acute myeloid leukemia 2.5 Chronic recurrent multifocal osteomyelitis Hodgkin lymphoma 2.4* 391 Classic Hodgkin lymphoma 2.38* 352 Galactosemia 2.1* Classic galactosemia 2.1* Autoimmune hemolytic anemia 2.02* 1866 Focal, segmental or multifocal dystonia 2.0* 729 Polycythemia vera 1.9* Pleural mesothelioma 1.9* 102 Multiple system atrophy 1.8 Testicular seminomatous germ cell 842 tumor 1.71* 355 Gaucher disease 1.7* Acute transverse myelitis Cushing 1.55* 512 Metachromatic leukodystrophy 1.5* 92 Juvenile idiopathic arthritis 1.5* 35 Propionic acidemia Familial melanoma 1.5* incidence(/,000) Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March

14 26106 Hereditary diffuse gastric cancer 1.5* Myelodysplastic 1.5* 2103 Guillain-Barré Scleroderma Amyotrophic lateral sclerosis Isolated aniridia 1.31* 77 Aniridia 1.3* 635 Neuroblastoma Chronic myeloid leukemia 1.25* Proximal spinal muscular atrophy type * 2 Non-seminomatous germ cell tumor of * testis 2137 Chronic autoimmune hepatitis 1.2 Epstein-Barr virus-associated gastric carcinoma Legionellosis 1.1* Proximal spinal muscular atrophy type * Malignant tumor of penis 1.075* Non-functioning pituitary adenoma Beta-thalassemia Pfeiffer 1.0* 727 Microscopic polyangiitis 1.0* Malignant peripheral nerve sheath 3148 tumor Cystic echinococcosis 1.0* 2781 Osteopetrosis 1.0* Gastrointestinal stromal tumor Myelofibrosis with myeloid metaplasia 1.0* Liposarcoma 1.0* Craniopharyngioma Hyperplastic polyposis Solitary rectal ulcer 1.0* 2023 Undifferentiated pleomorphic sarcoma 0.9* 2467 Systemic mastocytosis 0.9* Waldenström macroglobulinemia 0.81* Bone sarcoma 0.8* 930 Idiopathic achalasia Primary cutaneous lymphoma 0.75* 900 Granulomatosis with polyangiitis 0.7* Oligodendroglial tumor 0.7* 070 Progressive non-fluent aphasia 0.7* Adenocarcinoma of esophagus Progressive supranuclear palsy Primary sclerosing cholangitis Japanese encephalitis 0.65* incidence(/,000) Acute disseminated encephalomyelitis 0.6* Porphyria cutanea tarda 0.6* 780 Rhabdomyosarcoma 0.59* Mycosis fungoides and variants 0.59* 732 Polymyositis 0.585* Squamous cell carcinoma of penis 0.57* 221 Dermatomyositis 0.55* ACTH-dependent Cushing Myasthenia gravis Well-differentiated liposarcoma 0.51* 191 Cockayne 0.5* 2584 Classic mycosis fungoides 0.5* 980 Absence of the pulmonary artery 0.5* Uveal melanoma 0.5* 820 Sneddon 0.4* T-cell large granular lymphocyte leukemia 0.4* Chronic primary adrenal insufficiency 0.4* 399 Huntington disease St. Louis encephalitis 0.38* Stevens-Johnson 0.36* 963 Acromegaly Relapsing polychondritis IgG4-related retroperitoneal fibrosis 0.35* Cerebral sinovenous thrombosis 0.35* Kaposi sarcoma 0.34* 533 Listeriosis Anisakiasis 0.32 Proximal spinal muscular atrophy type * Herpes simplex encephalitis 0.3 Hereditary pheochromocytomaparaganglioma Desmoid tumor 0.3* MALT lymphoma 0.3* Infant botulism 0.3* Acute generalized exanthematous pustulosis Juvenile dermatomyositis Hairy cell leukemia 0.29* Cutaneous neuroendocrine carcinoma Dedifferentiated liposarcoma 0.27* Proximal spinal muscular atrophy type * Malignant melanoma of the mucosa 0.26* Insulinoma Idiopathic acute transverse myelitis 0.25* incidence(/,000) Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March

15 Classic endocrine tumor of appendix Chondrosarcoma 0.24* 668 Osteosarcoma 0.23* 1332 Medullary thyroid carcinoma 0.22* Pancreatic endocrine tumor 0.21* 301 Ependymal tumor 0.2* Cushing disease 0.2* Ependymoma 0.2* Primary hepatic neuroendocrine 085 carcinoma Takayasu arteritis 0.19* Toxic epidermal necrolysis 0.19 Primary cutaneous CD30+ T-cell 541 lymphoproliferative disease 0.18* Eosinophilic granulomatosis with 183 polyangiitis 0.18* 543 Burkitt lymphoma 0.17* 3398 Thymic epithelial neoplasm 0.17* 142 Anaplastic thyroid carcinoma 0.17* 284 Alveolar echinococcosis 0.16* 204 Creutzfeldt-Jakob disease Meningioma 0.15* Transmissible spongiform encephalopathy 0.15* Pediatric hepatocellular carcinoma 0.15* 654 Nephroblastoma 0.14* Thymoma 0.14* 319 Ewing sarcoma 0.13* Malignant sex cord stromal tumor of ovary 0.13* Rare urogenital tumor 0.13* 913 Zollinger-Ellison Optic pathway glioma 0.12 Nodular lymphocyte predominant Hodgkin lymphoma 616 Medulloblastoma 0.11* 520 Acute promyelocytic leukemia 0.11* 112 Bartter 0.1* 509 Leptospirosis 0.1* Autosomal dominant hyper-ige * 2382 Lennox-Gastaut 0.1* 514 Acute monoblastic leukemia 0.1* Cardiodysrhythmic potassium-sensitive * periodic paralysis Pseudomyxoma peritonei Caroli disease Myxoid/round cell liposarcoma 0.1* incidence(/,000) Miller-Fisher 0.1* Foodborne botulism 0.1* Wound botulism 0.1* Anti-glomerular basement membrane 375 disease 0.08* Malignant germ cell tumor of ovary 0.08* Acquired hemophilia Congenital erythropoietic porphyria 0.065* 790 Retinoblastoma 0.05* 1267 Botulism 0.05* Pleomorphic liposarcoma 0.05* Idiopathic pulmonary hemosiderosis * 331 Congenital factor XIII 0.04* Juvenile Huntington disease 0.04* 385 Pituitary carcinoma 0.04* Autoimmune pulmonary alveolar 747 proteinosis Non-hereditary retinoblastoma 0.038* 2573 Moyamoya disease 0.035* 290 Congenital rubella 0.03* 1501 Adrenocortical carcinoma 0.03* Reticular dysgenesis 0.03* Acquired epidermolysis bullosa 0.03* Spermatocytic seminoma 0.03* Goblet cell carcinoma Hepatoblastoma 0.02* 1957 Esthesioneuroblastoma 0.02* 1183 Opsoclonus-myoclonus 0.02* 143 Parathyroid carcinoma 0.02* Placental site trophoblastic tumor 0.02* Pineoblastoma 0.02* Astroblastoma 0.02* Sex cord-stromal tumor of testis 0.02* Pulmonary venoocclusive disease 0.015* 538 Lymphangioleiomyomatosis Acute intermittent porphyria 0.013* Autosomal erythropoietic protoporphyria 0.012* 2030 Fibrosarcoma 0.01* Adamantinoma 0.01* Choroid plexus carcinoma 0.01* Porphyria variegata 0.008* Pleuropulmonary blastoma family tumor susceptibility Glucagonoma 0.005* Somatostatinoma * incidence(/,000) Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March

16 List of diseases or groups of diseases by decreasing number of published cases or families of published cases Ebola hemorrhagic fever Kikuchi-Fujimoto disease 2309 Pachyonychia congenita Rosaï-Dorfman disease 64 Alström 1917 Fetal methylmercury Rickettsialpox 85 Congenital dyserythropoietic anemia Nipah virus disease 167 Chédiak-Higashi 26 Methylmalonic acidemia with homocystinuria ,XX ovotesticular disorder of sex development 2930 Cronkhite-Canada 3261 Autoimmune lymphoproliferative Familial primary hypomagnesemia PFAPA Erdheim-Chester disease Rhabdoid tumor Central neurocytoma Methylmalonic acidemia with homocystinuria, type cblc Marburg hemorrhagic fever AGel amyloidosis 22 4-hydroxybutyric aciduria Vitamin B12-unresponsive methylmalonic acidemia type mut Insulin autoimmune Norrie disease Bloom Epidermal nevus Alpha-heavy chain disease Tracheobronchopathia osteochondroplastica Oncogenic osteomalacia Primary orthostatic tremor Vulvovaginal gingival Leukocyte adhesion Pulmonary blastoma Hereditary cerebral hemorrhage with amyloidosis Susac 1556 Cutis marmorata telangiectatica congenita 570 Moebius 3071 Costello 157 Carnitine palmitoyltransferase II 184 Cherubism 1340 Cardiofaciocutaneous 1328 Camurati-Engelmann disease 1896 EEC 2092 Focal dermal hypoplasia 2909 Rothmund-Thomson 1467 Cogan 2330 Kasabach-Merritt 3347 Mounier-Kühn Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March

17 530 Lipoid proteinosis 41 Dyschromatosis symmetrica hereditaria 482 Kimura disease 525 Lichen planopilaris 840 Syringocystadenoma papilliferum 73 Gorham-Stout disease Desmoplastic small round cell tumor Acquired von Willebrand Carnitine palmitoyl transferase II, myopathic form Superficial siderosis Scleromyxedema Autoimmune necrotizing myopathy 237 Duplication of urethra 501 Lafora disease 500 Noonan with multiple lentigines Acute encephalopathy with biphasic seizures and late reduced diffusion 2070 Eosinophilic gastroenteritis Capillary malformation - arteriovenous malformation 2908 Kindler Partial acquired lipodystrophy 006 ABeta amyloidosis, Dutch type Meesmann corneal dystrophy Maffucci 373 Simpson-Golabi-Behmel Lupus erythematosus tumidus q13.3 microdeletion 2710 Oculodentodigital dysplasia Good Megacystis-microcolon-intestinal hypoperistalsis Lhermitte-Duclos disease Muir-Torre Pachydermoperiostosis Micro Trichothiodystrophy 1598 Monosomy 18p 193 Cohen 1059 Blue rubber bleb nevus 3165 Eosinophilic fasciitis Alpha-thalassemia-X-linked intellectual disability Gollop-Wolfgang complex 1980 Bilateral striopallidodentate calcinosis M 575 Muckle-Wells 559 Marinesco-Sjögren 343 Hyperimmunoglobulinemia D with periodic fever 414 Gyrate atrophy of choroid and retina 1451 CINCA 452 X-linked lissencephaly with abnormal genitalia 317 Erythrokeratodermia variabilis 302 Epidermodysplasia verruciformis 2088 Glycogen storage disease due to GLUT Tufted angioma 220 Denys-Drash Hypocomplementemic urticarial vasculitis Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March

18 523 Hereditary leiomyomatosis and renal cell cancer 679 Malignant atrophic papulosis Congenital pseudoarthrosis of clavicle Subcorneal pustular dermatosis Primary effusion lymphoma Monosomy 22q Congenital erythropoietic porphyria GM1 gangliosidosis type X-linked sideroblastic anemia Acquired angioedema Robinow Ligneous conjunctivitis Multicentric reticulohistiocytosis Hemochromatosis type Madras motor neuron disease Pulmonary artery coming from the aorta Limited systemic sclerosis Rothmund-Thomson type Infantile digital fibromatosis Right temporal lobar atrophy Familial primary hypomagnesemia with hypercalciuria and nephrocalcinosis 1540 Jackson-Weiss Eosinophilic colitis 28 Vitamin B12-responsive methylmalonic acidemia 1465 Coffin-Siris Epithelial recurrent erosion dystrophy 1475 Renal coloboma Iatrogenic botulism Thiel-Behnke corneal dystrophy Celiac disease, epilepsy and cerebral calcification 1459 Megalencephaly-capillary malformationpolymicrogyria q11 microdeletion Malignant triton tumor Autoerythrocyte sensitization 1522 Craniometaphyseal dysplasia 1359 Carney complex Congenital cataracts - facial dysmorphism - neuropathy 324 Persistent polyclonal B-cell lymphocytosis 226 Dihydropteridine reductase 3467 Hereditary xanthinuria 3103 Roberts 2048 Foix-Chavany-Marie 2108 Hallermann-Streiff 3197 Hereditary hyperekplexia 3265 Humero-radial synostosis 2637 Microcephalic osteodysplastic primordial dwarfism type II 662 Yellow nail Infantile neuroaxonal dystrophy Tyrosinemia type Schnitzler 188 Systemic capillary leak Disseminated peritoneal leiomyomatosis X-linked creatine transporter Glycogen storage disease due to glucose-6- phosphatase type b Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March

19 Isaac Pediatric Castleman disease Carney triad Peritoneal cystic mesothelioma Familial isolated pituitary adenoma Acute zonal occult outer retinopathy CACH Focal facial dermal dysplasia Bazex Bazex-Dupré-Christol MULIBREY nanism Regional odontodysplasia L-2-hydroxyglutaric aciduria IgG4-related hepatopathy Mendelian susceptibility to mycobacterial diseases due to complete IL12RB Microvillus inclusion disease Immune dysregulation-polyendocrinopathyenteropathy-x-linked Aorto-ventricular tunnel Reticulate acropigmentation of Kitamura Free sialic acid storage disease Leukoencephalopathy with brain stem and spinal cord involvement - high lactate LCAT Feingold Isolated cloverleaf skull Aicardi-Goutières Hereditary motor and sensory neuropathy, Okinawa type Gamma-heavy chain disease Feingold type 1 Combined hamartoma of the retina and retinal pigment epithelium Ulnar-mammary Prader-Willi-like Focal myositis Schnyder corneal dystrophy Kleefstra Postaxial polydactyly-anterior pituitary anomaliesfacial dysmorphism Hyperornithinemia-hyperammonemiahomocitrullinuria Nager Familial primary hypomagnesemia with hypercalciuria and nephrocalcinosis without severe ocular involvement Myoclonic epilepsy of infancy Hypomyelination-hypogonadotropichypogonadism-hypodontia Pitt-Hopkins-like 349 Fucosidosis 800 Schwartz-Jampel 45 Adenosine monophosphate deaminase 833 Encephalopathy due to sulfite oxidase 2053 Freeman-Sheldon 2785 Osteopetrosis with renal tubular acidosis 2414 Congenital pulmonary lymphangiectasia 477 KID 291 Fetal varicella 2882 Sitosterolemia 274 Bernard-Soulier 869 Triple A 981 Internal carotid agenesis Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March

20 1507 Autosomal recessive Robinow 672 Pallister-Hall 2222 Hypertrichosis lanuginosa congenita 1826 Frontometaphyseal dysplasia 2780 Osteopathia striata - cranial sclerosis 2697 Arthrogryposis - renal dysfunction - cholestasis 2704 Ochoa 2342 Haim-Munk 3107 Autosomal dominant Robinow 572 Immuno by defective expression of HLA class Mitochondrial trifunctional protein 24 Fumaric aciduria 332 Congenital intrinsic factor 3243 Sweet 3319 Congenital amegakaryocytic thrombocytopenia 1929 Rasmussen subacute encephalitis 2478 Megalencephalic leukoencephalopathy with subcortical cysts Autosomal agammaglobulinemia Tangier disease Primary hypomagnesemia with secondary hypocalcemia PHACE Aromatic L-amino acid decarboxylase 898 Wagner disease 724 Idiopathic acute eosinophilic pneumonia Rapid-onset dystonia-parkinsonism Immuno due to selective antipolysaccharide antibody McLeod neuroacanthocytosis Junctional epidermolysis bullosa - pyloric atresia Recessive dystrophic epidermolysis bullosa inversa Trichorhinophalangeal type 1 and Retinal arterial tortuosity Acquired generalized lipodystrophy Monoclonal Ig light chain-associated Fanconi Autosomal dominant hypophosphatemic rickets Helicoid peripapillary chorioretinal degeneration Cytophagic histiocytic panniculitis Multicentric Castleman disease Recessive hereditary methemoglobinemia type Spastic paraplegia type Rothmund-Thomson type q44 microdeletion Lichen planus pemphigoides Autosomal dominant macrothrombocytopenia H Pulmonary capillary hemangiomatosis Hemidystonia-hemiatrophy 1293 Brachyolmia 1310 Caffey disease 1221 Cheilitis glandularis 351 Galactosialidosis Attenuated Chédiak-Higashi Multiple self-healing squamous epithelioma 502 Langer-Giedion Brooke-Spiegler Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March

21 Monosomy Xp21 Autosomal dominant neovascular inflammatory vitreoretinopathy Silent sinus Malignant migrating partial seizures of infancy Mohr-Tranebjaerg Isolated ectopia lentis Prolidase 90 Progressive non-infectious anterior vertebral 2062 fusion Spinocerebellar ataxia type McKusick-Kaufman Allan-Herndon-Dudley Frasier Floating-Harbor Kleefstra due to 9q34 microdeletion Uhl anomaly 84 Glycogen storage disease due to LAMP Metatropic dysplasia Focal facial dermal dysplasia type I Reis-Bücklers corneal dystrophy Farber disease Early myoclonic encephalopathy Liddle Acroosteolysis dominant type Peters plus Guanidinoacetate methyltransferase Arterial tortuosity Wells Penile agenesis 80 Thiamine-responsive megaloblastic anemia D-2-hydroxyglutaric aciduria Riboflavin transporter 80 Autosomal recessive early-onset inflammatory bowel disease Alpha-thalassemia-myelodysplastic Acrodysostosis Encephalocraniocutaneous lipomatosis Cerebro-costo-mandibular Hemochromatosis type IRIDA Homocystinuria without methylmalonic aciduria 73 Mutilating palmoplantar keratoderma with 659 periorificial keratotic plaques Familial primary hypomagnesemia with 72 hypercalciuria and nephrocalcinosis with severe ocular involvement 2671 Neu-Laxova Schimke immuno-osseous dysplasia Ring chromosome Purine nucleoside phosphorylase Diffuse neonatal hemangiomatosis 70 6 Median cleft lip/mandibule Melnick-Needles Pseudohypoaldosteronism type Carpenter Bullous systemic lupus erythematosus Familial LCAT GM1 gangliosidosis type 3 70 Autosomal dominant mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR DITRA Amyotrophic lateral sclerosis type 4 70 Congenital adrenal hyperplasia due to 3-betahydroxysteroid dehydrogenase Congenital hereditary endothelial dystrophy type I Ear-patella-short stature Cap polyposis ICF Glutathione synthetase Kenny-Caffey WHIM Brittle cornea 65 Hereditary hyperferritinemia with congenital 163 cataracts Renpenning Ehlers-Danlos, periodontitis type Perrault Intellectual disability - sparse hair - brachydactyly Pearson Dyggve-Melchior-Clausen disease Pancreatoblastoma Griscelli disease Acromicric dysplasia Bowen-Conradi Wolcott-Rallison CHILD Galloway-Mowat Shprintzen-Goldberg Peters anomaly Carnitine-acylcarnitine translocase 60 Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March

22 3338 Toriello-Carey Double uterus - hemivagina - renal agenesis Acquired hypertrichosis lanuginosa Gray platelet Pseudo-von Willebrand disease Paraneoplastic pemphigus 60 Vitamin B12-responsive methylmalonic acidemia type cbla 60 Mandibulofacial dysostosis-microcephaly Autosomal recessive cutis laxa type Haddad Sea-blue histiocytosis Sagliker Refsum disease KBG ALG6-CDG Blepharophimosis-intellectual disability Autosomal recessive ataxia, Beauce type 57 Autosomal recessive severe congenital neutropenia due to G6PC Adenylosuccinate lyase Chylomicron retention disease Microphthalmia with linear skin defects Sporotrichosis Mazabraud PELVIS 54 Autosomal recessive spastic ataxia with leukoencephalopathy Interstitial granulomatous dermatitis with arthritis Distal arthrogryposis type Perry Hereditary cryohydrocytosis with normal stomatin Zimmermann-Laband Angiocentric glioma Spinocerebellar ataxia type Multiple sulfatase Triose phosphate-isomerase Cholestasis-lymphedema Juvenile Paget disease Rotor Monosomy Seckel Familial progressive cardiac conduction defect Waardenburg-Shah Ring chromosome Acromesomelic dysplasia, Maroteaux type Carnitine palmitoyl transferase 1A Ascher Borjeson-Forssman-Lehmann Branchio-oculo-facial Ocular motor apraxia, Cogan type Fibular aplasia - ectrodactyly Hypotrichosis with juvenile macular degeneration Ring chromosome Desbuquois Neutral lipid storage disease Geroderma osteodysplastica Donnai-Barrow Hennekam Blepharo-cheilo-odontic Juvenile hyaline fibromatosis Langer mesomelic dysplasia Marden-Walker LOC Pitt-Hopkins Partial pancreatic agenesis 50 Hemolytic anemia due to glucophosphate 712 isomerase Paris-Trousseau thrombocytopenia Deafness-onychodystrophy Zlotogora-Ogur Familial glucocorticoid Ehrlichiosis Granulomatous slack skin Spontaneous periodic hypothermia Benign paroxysmal torticollis of infancy Rhombencephalosynapsis Goldmann-Favre DOORS Isolated congenital anonychia GM1 gangliosidosis type Oguchi disease Snowflake vitreoretinal degeneration Xeroderma pigmentosum variant Autosomal dominant cutis laxa Congenital analbuminemia 50 Cystic leukoencephalopathy without megalencephaly Fetal Gaucher disease Paroxysmal exertion-induced dyskinesia 50 Glycogen storage disease due to phosphoglycerate mutase Primary hyperoxaluria type 3 50 Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March

23 Auriculocondylar Autosomal recessive dopa-responsive dystonia Hepatic amyloidosis with intrahepatic cholestasis Lissencephaly with cerebellar hypoplasia type B Hashimoto-Pritzker p13.3 microduplication Poikiloderma with neutropenia Neuroferritinopathy Trisomy 10p Spinocerebellar ataxia type Adult polyglucosan body disease Onychomatricoma 50 Xeroderma pigmentosum complementation group C CLIPPERS 50 Multicentric osteolysis-nodulosis-arthropathy spectrum Chondromyxoid fibroma Phalangeal microgeodic Familial reactive perforating collagenosis 50 Keratoderma hereditarium mutilans with ichthyosis Jalili Corticosteroid-sensitive aseptic abscess 49 Mendelian susceptibility to mycobacterial diseases due to complete IL12B Navajo neurohepatopathy Weaver Pityriasis rubra pilaris 48 Rapid-onset childhood obesity - hypothalamic dysfunction - hypoventilation - autonomic dysregulation Hypoglossia-hypodactyly Coxopodopatellar Osteogenesis imperfecta type q21.1 microduplication Schinzel-Giedion X-linked severe congenital neutropenia Kostmann Cone dystrophy with supernormal rod response Postorgasmic illness Aneurysm-osteoarthritis 45 Mitochondrial DNA depletion, myopathic form Syndromic diarrhea 44 Seborrhea-like dermatitis with psoriasiform elements Dopa-responsive dystonia due to sepiapterin reductase Mosaic variegated aneuploidy Distal 7q11.23 microdeletion Oculoauriculofrontonasal Congenital short bowel Bruck 40 9 Tetrasomy X 40 Congenital cataract - hypertrophic cardiomyopathy mitochondrial myopathy 2971 Peroxisomal acyl-coa oxidase Distal trisomy 6p Trisomy 5p Trisomy 12p 40 Congenital generalized hypertrichosis, Ambras 1023 type Methimazole embryofetopathy Transcobalamin Hypertrichotic osteochondrodysplasia, Cantu type Ichthyosis follicularis - alopecia - photophobia Matthew-Wood Mandibuloacral dysplasia De Barsy 40 Epidermolysis bullosa simplex with muscular 257 dystrophy 40 Autosomal dominant hypohidrotic ectodermal 1810 dysplasia Ethylmalonic encephalopathy DEND Autosomal recessive cutis laxa type Distal trisomy 10q Distal monosomy 10q Hepatoerythropoietic porphyria Macrocephaly-autism q14.3 microdeletion Congenital alveolar capillary dysplasia Ameloblastic carcinoma Acral peeling skin Bullous diffuse cutaneous mastocytosis Acrodysostosis with multiple hormone resistance Congenital reticular ichthyosiform erythroderma Generalized eruptive keratoacanthoma Cranioectodermal dysplasia Oculocerebrocutaneous GAPO Hypotrichosis simplex 38 Autosomal dominant rhegmatogenous retinal detachment Duplication of the pituitary gland 38 Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March

24 1993 Pai Isolated succinate-coq reductase Late-onset junctional epidermolysis bullosa Dysequilibrium Spondyloenchondrodysplasia Lisch epithelial corneal dystrophy 36 Hereditary North American Indian childhood cirrhosis Polymicrogyria due to TUBB2B mutation 36 Benign infantile focal epilepsy with midline spikes and wave during sleep 446 Neonatal hemochromatosis Congenital bronchobiliary fistula 35 Hereditary sensory and autonomic neuropathy 970 type Cobb Distal monosomy 6p Mu-heavy chain disease X-linked endothelial corneal dystrophy Acrocallosal Ring chromosome Antley-Bixler Gómez-López-Hernández Malonic aciduria Pyogenic arthritis - pyoderma gangrenosum - acne Obesity due to MC3R Phakomatosis pigmentokeratotica Intellectual disability-strabismus 34 Short stature-optic atrophy-pelger-huët anomaly Neonatal antiphospholipid Short rib-polydactyly, Majewski type Locked-in Catel-Manzke Autosomal dominant osteopetrosis type Marshall-Smith Richieri Costa-Pereira Methylcobalamin type cblg Succinyl-CoA:3-ketoacid CoA transferase Hoyeraal-Hreidarsson Polycystic ovaries - urethral sphincter dysfunction Björnstad Hemochromatosis type SHORT Filippi ALDH18A1-related De Barsy Segmental odontomaxillary dysplasia Supernumerary nostril MC 32 Chronic diarrhea due to guanylate cyclase 2C overactivity 32 Autosomal recessive ataxia due to ubiquinone Lower motor neuron with late-adult onset Ring chromosome 9 31 Glycogen storage disease due to muscle 371 phosphofructokinase Postaxial acrofacial dysostosis Mevalonic aciduria 30 Aniridia-cerebellar ataxia-intellectual disability Opsismodysplasia 30 Glycogen storage disease due to muscle 715 phosphorylase kinase Trisomy 8q Acropectorovertebral dysplasia Nakajo-Nishimura Congenital intrauterine infection-like Baller-Gerold Restrictive dermopathy Crisponi Cranio-osteoarthropathy Otospondylomegaepiphyseal dysplasia Scalp-ear-nipple Osteocraniostenosis Omodysplasia 30 Blepharophimosis-intellectual disability, Ohdo type Microcephalic osteodysplastic primordial dwarfism types I and III 2399 Nasopalpebral lipoma - coloboma - telecanthus 30 5 Pyle disease Wrinkly skin Otopalatodigital Humero-radio-ulnar synostosis Cenani-Lenz Tricho-dento-osseous Baraitser-Winter Weaver-Williams Woodhouse-Sakati Perlman Neurometabolic disorder due to serine Obesity due to congenital leptin Transient bullous dermolysis of the newborn 30 Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March

25 79456 Diffuse cutaneous mastocytosis Fish-eye disease Encephalopathy due to hydroxykynureninuria methylbutyryl-CoA dehydrogenase 30 Anophthalmia/microphthalmia - esophageal atresia Monosomy 9q Ring dermoid of cornea 30 Spondylometaphyseal dysplasia, 'corner fracture' type 30 Spondyloepimetaphyseal dysplasia congenita, Strudwick type 30 Autosomal dominant polycystic kidney disease type 1 with tuberous sclerosis Hereditary folate malabsorption 30 Camptodactyly - tall stature - scoliosis - hearing loss Christianson Keutel Spinocerebellar ataxia type Bohring-Opitz Laryngo-tracheo-esophageal cleft type Linear atrophoderma of Moulin Fleck corneal dystrophy 30 Xeroderma pigmentosum-cockayne complex 30 Carnitine palmitoyl transferase II, severe infantile form Hughes-Stovin Linear focal dermal elastosis q11q13 microduplication Neurologic Waardenburg-Shah Glossopalatine ankylosis 30 Severe neonatal-onset encephalopathy with microcephaly IRVAN Reunion Island's Larsen Dianzani autoimmune lymphoproliferative disease 30 Xeroderma pigmentosum complementation group D Isolated cryptophthalmia Infant epilepsy with migrant focal crisis Symmetrical thalamic calcifications Orofaciodigital type 4 29 Leukoencephalopathy with bilateral anterior temporal lobe cysts Hypertrichosis cubiti - short stature Wilson-Turner Craniolenticulosutural dysplasia 28 Autosomal dominant Charcot-Marie-Tooth disease type 2N Gastric adenocarcinoma and proximal polyposis of the stomach Autosomal dominant focal dystonia, DYT25 28 Familial episodic pain with predominantly lower limb involvement 466 Fatal familial insomnia Metaphyseal anadysplasia Methylcobalamin type cble 27 Noonan -like disorder with loose anagen hair 2623 Geleophysic dysplasia Limb-mammary LIG Benign concentric annular macular dystrophy 27 Hereditary diffuse leukoencephalopathy with axonal spheroids and pigmented glia 27 X-linked central congenital hypothyroidism with late-onset testicular enlargement Böök Acitretin/etretinate embryopathy Spinocerebellar ataxia type Multiple congenital anomalies due to 14q maternally expressed gene defect 26 Motor developmental delay due to 14q paternally expressed gene defect 26 Syndactyly - camptodactyly and clinodactyly of fifth fingers - bifid toes C 25 Palmoplantar keratoderma-spastic paralysis Spinocerebellar ataxia type Metachondromatosis Wiedemann-Rautenstrauch Yunis-Varon Omenn Schöpf-Schulz-Passarge Plummer-Vinson Atelosteogenesis type III Atelosteogenesis type II 25 Hepatic veno-occlusive disease immuno Congenital megacalycosis IMAGe q32q33 microdeletion Porokeratotic eccrine ostial and dermal duct nevus Chudley-McCullough Mycophenolate mofetil embryopathy 25 Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March

26 Self-healing collodion baby 25 Autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures Trisomy 18p Bartsocas-Papas Infantile onset spinocerebellar ataxia Carnosinemia Spondylocarpotarsal synostosis 24 Distal myopathy with early respiratory muscle involvement Central cloudy dystrophy of Francois 24 Hyperphosphatasia-intellectual disability X-linked spastic paraplegia type Hypercholesterolemia due to cholesterol 7alphahydroxylase Pyogenic bacterial infections due to MyD Pseudohypoaldosteronism type 2D 24 Autosomal dominant cerebellar ataxia, deafness and narcolepsy 24 Familial cutaneous telangiectasia and oropharyngeal predisposition cancer 24 PURA-related severe neonatal hypotonia-seizuresencephalopathy due to a point mutation q24 microdeletion Potocki-Shaffer Autosomal recessive omodysplasia Transaldolase Familial hypercholanemia Kleefstra due to a point mutation Pontocerebellar hypoplasia type Combined immuno due to LRBA Pierson Ehlers-Danlos, musculocontractural type Split hand - split foot - deafness 22 Autosomal dominant deafness-onychodystrophy Familial thoracic aortic aneurysm and aortic dissection Genitopatellar Acro-pectoral Familial thyroglossal duct cyst Monocytopenia with susceptibility to infections 22 Generalized congenital lipodystrophy with myopathy Hypotonia-cystinuria Childhood apraxia of speech Lethal arteriopathy due to fibulin-4 22 Developmental delay with autism spectrum disorder and gait instability Pontine tegmental cap dysplasia 22 Xeroderma pigmentosum complementation group F Childhood-onset autosomal recessive myopathy with external ophthalmoplegia Focal facial dermal dysplasia type II Scapuloperoneal spinal muscular atrophy methylglutaconic aciduria type Myhre Dehydratase Dopamine beta-hydroxylase Odonto-tricho-ungual-digito-palmar 21 Autosomal dominant intermediate Charcot-Marie Tooth disease type E Nephrogenic of inappropriate antidiuresis Hyperuricemia - anemia - renal failure Sudden infant death - dysgenesis of the testes 21 Isolated autosomal dominant hypomagnesemia, Glaudemans type 21 Autosomal dominant focal non-epidermolytic palmoplantar keratoderma with plantar blistering Fatal multiple mitochondrial dysfunction type 1 21 Familial episodic pain with predominantly upper body involvement Focal facial dermal dysplasia type IV Hereditary orotic aciduria Alpha-N-acetylgalactosaminidase Carey-Fineman-Ziter Acrorenal 20 Hypertrichosis-acromegaloid facial appearance Acromegaloid facial appearance Focal facial dermal dysplasia type III Hypertelorism, Teebi type Craniodiaphyseal dysplasia Vici Cataract - intellectual disability - hypogonadism COFS Superficial epidermolytic ichthyosis Orofaciodigital type 8 20 Laryngeal abductor paralysis - intellectual 2375 disability Lacrimoauriculodentodigital RAPADILINO 20 Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March

27 Blepharophimosis-intellectual disability, SBBYS type 2847 Pericardial and diaphragmatic defect Deafness - lymphedema - leukemia Isolated anterior cervical hypertrichosis Arrhinia Pyruvate dehydrogenase E Occipital horn Neuroectodermal melanolysosomal disease Juvenile temporal arteritis Aromatase Pure hair and nail ectodermal dysplasia methylglutaconic aciduria type Tyrosinemia type Timothy 20 Radio-ulnar synostosis - amegakaryocytic thrombocytopenia 20 Bleeding diathesis due to a collagen receptor defect Angel-shaped phalango-epiphyseal dysplasia Rubella panencephalitis MPI-CDG aminoadipic 2-oxoadipic aciduria Familial partial lipodystrophy, Köbberling type 20 Channelopathy-associated congenital insensitivity to pain Atypical lichen myxedematosus Posterior column ataxia - retinitis pigmentosa Keratosis palmaris et plantaris - clinodactyly Calvarial doughnut lesions - bone fragility 20 Alpha-thalassemia-intellectual disability linked to chromosome Spinocerebellar ataxia type Spinocerebellar ataxia type Fingerprint body myopathy Laryngo-tracheo-esophageal cleft type Autosomal recessive bestrophinopathy Czech dysplasia, metatarsal type Spinocerebellar ataxia type Bathing suit ichthyosis 20 Autosomal dominant Charcot-Marie-Tooth disease type 2M Acquired pseudoxanthoma elasticum Primary ciliary dyskinesia - retinitis pigmentosa 20 Localized junctional epidermolysis bullosa, non Herlitz type q33.1 microdeletion Palmoplantar keratoderma, Nagashima type Syndromic microphthalmia type Brain-lung-thyroid Cirrhosis-dystonia-polycythemiahypermanganesemia MEGDEL p13.11 microduplication 20 RAS-associated autoimmune leukoproliferative disease Cutaneous collagenous vasculopathy Atypical glycine encephalopathy 20 Mitochondrial DNA depletion, encephalomyopathic form with variable craniofacial anomalies Malan overgrowth Toriello-Lacassie-Droste Craniosynostosis, Boston type 19 Hereditary myopathy with lactic acidosis due to ISCU q terminal deletion 19 Hereditary inclusion body myopathy - joint contractures - ophthalmoplegia KRT14-related epidermolysis bullosa simplex 19 Hypomyelination with atrophy of basal ganglia and cerebellum Progressive cavitating leukoencephalopathy Polyvalvular heart disease p22 microdeletion Adult intestinal botulism 19 Polyneuropathy - hearing loss - ataxia - retinitis pigmentosa - cataract Fixed pigmented erythema 19 Congenital muscular dystrophy due to phosphatidylcholine biosynthesis defect MEND New-onset refractory status epilepticus Schilbach-Rott Van den Ende-Gupta 18 Autosomal dominant primary hypomagnesemia with hypocalciuria Terminal osseous dysplasia - pigmentary defects 18 Spondylometaphyseal dysplasia - cone-rod dystrophy 18 Carnitine palmitoyl transferase II, neonatal form q23.1 microdeletion Charcot-Marie-Tooth disease type 2P Familial dyskinesia and facial myokymia Activated PIK3-delta 18 Methylmalonic acidemia with homocystinuria, type cblx 18 Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March

28 Didymosis aplasticosebacea Temtamy preaxial brachydactyly Joubert with oculorenal defect Marshall Camptodactyly - taurinuria Congenital lethal erythroderma Aminopterin/methotrexate embryofetopathy Circumscribed palmoplantar hypokeratosis 17 Methylmalonic acidemia with homocystinuria, type cbld Spondyloepimetaphyseal dysplasia, PAPSS2 type Leukocyte adhesion type III Congenital erosive and vesicular dermatosis Action myoclonus-renal failure Pseudohypoaldosteronism type 2E Hereditary inclusion body myopathy type 4 17 Autoimmune lymphoproliferative due to CTLA4 haploinsuffiency 17 Chronic atrial and intestinal dysrhythmia Ovarioleukodystrophy Congenital atransferrinemia GTP cyclohydrolase I Ring chromosome Ablepharon macrostomia Autosomal recessive facio-digito-genital Orofaciodigital type 3 16 Glycogen storage disease due to hepatic glycogen 2089 synthase Microgastria - limb reduction defect Metaphyseal chondrodysplasia, Jansen type 16 Obesity due to prohormone convertase I Orbital leiomyoma Dysspondyloenchondromatosis Juberg-Marsidi Acyl-CoA dehydrogenase Infantile dystonia-parkinsonism 16 Hypoplastic pancreas-intestinal atresia-hypoplastic gallbalder Intestinal obstruction in the newborn due to guanylate cyclase 2C Primary progressive apraxia of speech Distal 17p13.1 microdeletion Hereditary neutrophilia 16 Congenital sideroblastic anemia-b-cell immuno-periodic fever-developmental delay Odonto-onycho-dermal dysplasia Taurodontia - absent teeth - sparse hair Meacham Umbilical cord ulceration - intestinal atresia Von Voss-Cherstvoy 15 Congenital membranous nephropathy due to maternal anti-neutral endopeptidase alloimmunization 15 Immuno due to interleukin-1 receptorassociated kinase Methylmalonic acidemia with homocystinuria type cblf ALG1-CDG 15 Scleromyxedema without monoclonal gammopathy Isolated congenital anosmia Congenital sodium diarrhea 15 Hereditary sclerosing poikiloderma with tendon and pulmonary involvement CLOVE 15 Congenital muscular dystrophy due to LMNA mutation Lissencephaly due to TUBA1A mutation Spigelian hernia-cryptorchidism 15 Non-progressive cerebellar ataxia with intellectual disability Inverse Klippel-Trénaunay p13.11 microdeletion Complement component 3 15 Severe intellectual disability and progressive spastic paraplegia 15 Peripheral neuropathy-myopathy-hoarsenesshearing loss Obesity due to CEP Proximal myopathy with extrapyramidal signs 15 Intrauterine growth restriction-short stature-early adult-onset diabetes Thrombomodulin-related bleeding disorder Complete cryptophthalmia ADULT Atkin-Flaitz Absence of fingerprints - congenital milia Dermo-odonto dysplasia Craniofacial dyssynostosis Lateral meningocele Ring chromosome Autosomal recessive limb-girdle muscular dystrophy type 2G P2Y12 defect DPM1-CDG Oligocone trichromacy 14 Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March

29 90390 Anonychia - onychodystrophy Spondyloepimetaphyseal dysplasia, Missouri type q35 microduplication q21 microdeletion 14 Autosomal recessive limb-girdle muscular dystrophy type 2L Adult-onset dystonia-parkinsonism LAMB2-related infantile-onset nephrotic 14 Short stature-onychodysplasia-facial dysmorphism-hypotrichosis 14 Autosomal recessive mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR Distal 17p13.3 microdeletion 14 Retinal dystrophy with inner retinal dysfunction and ganglion cell anomalies Autosomal spastic paraplegia type Microcornea-myopic chorioretinal atrophytelecanthus Autosomal recessive severe congenital neutropenia due to JAGN X-linked scapuloperoneal muscular dystrophy Cerebro-facio-thoracic dysplasia Fibrochondrogenesis Blomstrand lethal chondrodysplasia Charcot-Marie-Tooth disease type 2H 13 Acute infantile liver failure due to synthesis defect of mtdna-encoded proteins Non-acquired combined pituitary hormone with spine abnormalities Hereditary progressive mucinous histiocytosis 13 Osteosclerosis-developmental delaycraniosynostosis Autosomal dominant spastic paraplegia type Hypertelorism-preauricular sinus-punctual pitsdeafness Congenital hereditary facial paralysis with variable hearing loss PENS 13 X-linked mendelian susceptibility to mycobacterial diseases Severe early-onset obesity-insulin resistance due to SH2B1 13 Familial steroid-resistant nephrotic with sensorineural deafness q21.11 microdeletion 13 Tall stature-intellectual disability-facial dysmorphism Episodic ataxia with slurred speech D,L-2-hydroxyglutaric aciduria Atypical hemolytic-uremic with DGKE q21 microdeletion 13 Pseudoxanthoma elasticum-like skin manifestations with retinis pigmentosa Progressive myoclonic epilepsy type Hyperostosis cranialis interna 13 Intellectual disability-expressive aphasia-facial dysmorphism Atrial tachyarrhythmia with short PR interval Acro-pectoro-renal dysplasia 12 Uveal coloboma-cleft lip and palate-intellectual 1473 disability 12 Alopecia-epilepsy-pyorrhea-intellectual disability Atelosteogenesis type I CODAS Coloboma of macula - brachydactyly type B Hypoparathyroidism - deafness - renal disease Hypertryptophanemia Torg-Winchester Distal myopathy with vocal cord weakness Ichthyosis - hypotrichosis - sclerosing cholangitis 12 Distal myopathy with posterior leg and anterior hand involvement 12 X-linked intellectual disability - macrocephaly macroorchidism 12 Hemolytic anemia due to adenylate kinase Spinocerebellar ataxia type 19/ Ballard 12 Hereditary sensory and autonomic neuropathy with spastic paraplegia q13.11 microdeletion Microduplication Xp11.22-p Dystonia Spondylo-megaepiphyseal-metaphyseal dysplasia Juvenile cataract - microcornea - renal glucosuria q16 deletion Muscular dystrophy, Selcen type 12 Cortical dysgenesis with pontocerebellar 570 hypoplasia due to TUBB3 mutation Autosomal recessive infantile hypercalcemia 12 Leukoencephalopathy-thalamus and brainstem anomalies-high lactate q overgrowth Distal tetrasomy 15q 12 Mendelian susceptibility to mycobacterial diseases due to complete IFNgammaR q24.3 microdeletion 12 Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March

30 q22.11q22.12 microdeletion q12 microduplication q22.13q22.2 microdeletion 12 Recessive intellectual disability - motor dysfunction - multiple joint contractures Progressive myoclonic epilepsy type Acute annular outer retinopathy 12 PRKAR1B-related neurodegenerative dementia with intermediate filaments 12 Hypohidrosis-enamel hypoplasia-palmoplantar keratoderma-intellectual disability 12 MYH7-related late-onset scapuloperoneal muscular dystrophy Foveal hypoplasia - presenile cataract Barber-Say 11 Amelogenesis imperfecta-nephrocalcinosis Fibular dimelia - diplopodia X-linked complicated corpus callosum dysgenesis Cooks Cleft palate-lateral synechia 11 Atrial septal defect - atrioventricular conduction 1479 defects X-linked intellectual disability, Snyder type Antecubital pterygium Short tarsus - absence of lower eyelashes Fuhrmann 11 Trichomegaly - retina pigmentary degeneration dwarfism ALG12-CDG Juvenile polyposis of infancy Familial acute necrotizing encephalopathy 11 Combined immuno due to DOCK Mammary-digital-nail 11 Autosomal dominant limb-girdle muscular dystrophy type 1H Familial congenital mirror movements 11 Hyperandrogenism due to cortisone reductase Familial scaphocephaly, McGillivray type Goldblatt Familial sick sinus 11 Leukonychia totalis - acanthosis-nigricans-like lesions - abnormal hair Infantile cerebellar-retinal degeneration q11.2 microdeletion Fatal infantile hypertonic myofibrillar myopathy Polyglucosan body myopathy 11 Facial dysmorphism - immuno - livedo short stature 11 Combined oxidative phosphorylation type Ventriculomegaly-cystic kidney disease q11.2 microdeletion Deletion 5q Acromesomelic dysplasia, Hunter-Thomson type Aase-Smith Infantile choroidocerebral calcification Hyperkeratosis-hyperpigmentation Boomerang dysplasia q37 microdeletion 10 Autosomal dominant palmoplantar keratoderma 1010 and congenital alopecia Arthrogryposis multiplex congenita - whistling face Pacman dysplasia Lowry-Wood 10 X-linked intellectual disability - Dandy-Walker 1568 malformation - basal ganglia disease - Seizures Acrofacial dysostosis, Rodríguez type Corneal dystrophy - perceptive deafness Greenberg dysplasia 10 Pancreatic hypoplasia - diabetes - congenital heart disease 2319 Juberg-Hayward Cerebral gigantism - jaw cysts 10 Gaucher disease - ophthalmoplegia cardiovascular calcification Flynn-Aird Lenz-Majewski hyperostotic dwarfism 10 Muscular atrophy - ataxia - retinitis pigmentosa diabetes mellitus 10 Hereditary myoclonus - progressive distal muscular atrophy 2439 Patterson-Stevenson-Fontaine Lethal Larsen-like Karsch-Neugebauer NPHP3-related Meckel-like Progeria - short stature - pigmented nevi Cardiocranial, Pfeiffer type Pelvis-shoulder dysplasia Phosphoenolpyruvate carboxykinase 10 Cerebellar ataxia - areflexia - pes cavus - optic 1171 atrophy - sensorineural hearing loss Thoracolaryngopelvic dysplasia XK aprosencephaly Acromelanosis Athabaskan brainstem dysgenesis 10 Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March

31 66637 Diaphanospondylodysostosis Cerebro-oculo-nasal 10 Hyperinsulinism due to short chain 3-hydroxylacyl CoA dehydrogenase Char Alpha-N-acetylgalactosaminidase type Alpha-N-acetylgalactosaminidase type Alpha-N-acetylgalactosaminidase type ALG3-CDG PPARG-related familial partial lipodystrophy 10 Localized lichen myxedematosus with mixed features of different subtypes 10 Body skin hyperlaxity due to vitamin K-dependent coagulation factor Centripetalis recessive dystrophic epidermolysis bullosa X-linked neurodegenerative, Hamel type 10 X-linked intellectual disability - hypotonia - facial dysmorphism - aggressive behavior 10 Diffuse palmoplantar keratoderma-acrocyanosis Pseudodiastrophic dysplasia Singleton-Merten dysplasia Hypomyelination - congenital cataract Syndromic X-linked intellectual disability Hunter-McAlpine craniosynostosis Zebra body myopathy Primary hyperoxaluria type Syndactyly type Encephalopathy due to prosaposin Perioral myoclonia with absences Spinocerebellar ataxia type Charcot-Marie-Tooth disease type 4H Lissencephaly with cerebellar hypoplasia type C Leukocyte adhesion type II Laron with immuno 10 Ehlers-Danlos due to tenascin-x Syndromic multisystem autoimmune disease due to Itch 10 Progressive supranuclear palsy - progressive non fluent aphasia 10 Dominant hypophosphatemia with nephrolithiasis or osteoporosis Familial clubfoot due to 17q23.1q microduplication Inhalational botulism Annular atrophic lichen planus 10 X-linked dominant chondrodysplasia, Chassaing Lacombe type Saldino-Mainzer Orofaciodigital type Heart-hand, Slovenian type 10 Combined immuno due to CRAC channel dysfunction Pontocerebellar hypoplasia type Congenital neuronal ceroid lipofuscinosis Heinz body anemia Cap myopathy 10 Sterile multifocal osteomyelitis with periostitis and pustulosis Benign familial nocturnal alternating hemiplegia of childhood Microcephaly-capillary malformation 10 Transient infantile hypertriglyceridemia and 293 hepatosteatosis Congenital pancreatic cyst 10 Segmental progressive overgrowth with fibroadipose hyperplasia Autosomal recessive congenital cerebellar ataxia due to MGLUR CANDLE p11.2p12.2 microdeletion Hyperinsulinism due to INSR Spondyloepiphyseal dysplasia, Maroteaux type 10 Xeroderma pigmentosum complementation group E Xeroderma pigmentosum complementation group G Hemihyperplasia-multiple lipomatosis Hemoglobinopathy Toms River 10 Pseudoxanthomatous diffuse cutaneous mastocytosis 10 Multiple congenital anomalies - hypotonia seizures TEMPI 10 ADNP-related multiple congenital anomaliesintellectual disability-autism spectrum disorder Huntington disease-like due to C9ORF expansions Hypomyelination with brain stem and spinal cord involvement and leg spasticity q24.1 microdeletion 10 Autosomal recessive cerebellar ataxia with lateonset spasticity Minimal pigment oculocutaneous albinism type 1 10 Temperature-sensitive oculocutaneous albinism type Pyruvate carboxylase, benign type 10 Intellectual disability-severe speech delay-mild dysmorphism 10 Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March

32 Autoimmune encephalopathy with parasomnia and obstructive sleep apnea GM2 gangliosidosis, AB variant 10 Fatal congenital hypertrophic cardiomyopathy due to glycogen storage disease 1345 Cardiomyopathy - cataract - hip spine disease Tricho-retino-dento-digital 9 Brachymorphism - onychodysplasia dysphalangism Curry-Jones Hypertelorism-microtia-facial clefting 9 8 Acro-cardio-facial Oculocerebrofacial, Kaufman type Mietens Gamma-glutamylcysteine synthetase 9 3-hydroxy-3-methylglutaryl-CoA synthase L-Arginine:glycine amidinotransferase Desmosterolosis Bosley-Salih-Alorainy Junctional epidermolysis bullosa inversa COG7-CDG Spondylometaphyseal dysplasia, Sedaghatian type X-linked intellectual disability - ataxia - apraxia 9 Macrostomia - preauricular tags - external ophthalmoplegia X-linked intellectual disability, Cantagrel type Craniosynostosis - anal anomalies - porokeratosis X-linked intellectual disability, Shashi type Laminopathy type Decaudain-Vigouroux Cardiac anomalies - heterotaxy 9 Combined immuno T+ B+ due to partial RAG1 9 X-linked intellectual disability - spastic quadriparesis 9 46,XY disorder of sex development - adrenal insufficiency due to CYP11A Autosomal recessive spastic paraplegia type Distal Xq28 microduplication p21.3 microdeletion Atypical Meigs 9 Developmental and speech delay due to SOX Cerebro-facio-articular 9 Autosomal dominant intermediate Charcot-Marie Tooth disease with neuropathic pain Adult-onset distal myopathy due to VCP mutation q23.1q23.2 microdeletion p15p16.1 microdeletion COG5-CDG 9 Moyamoya angiopathy-short stature-facial dysmorphism-hypergonadotropic hypogonadism 9 Periodic paralysis with later-onset distal motor neuropathy Lung agenesis - heart defect - thumb anomalies Moyamoya disease with early-onset achalasia Spinocerebellar ataxia type Oculocutaneous albinism type 7 9 Congenital microcephaly-severe encephalopathyprogressive cerebral atrophy Ketoacidosis due to monocarboxylate transporter STING-associated vasculopathy with onset in infancy Bamforth-Lazarus Campomelia, Cumming type Camptodactyly, Guadalajara type Brachydactyly - preaxial hallux varus Ataxia-deafness-intellectual disability 8 Autosomal recessive palmoplantar keratoderma 1366 and congenital alopecia Joubert with hepatic defect 8 Hydrocephalus - costovertebral dysplasia Sprengel anomaly Ankylosing vertebral hyperostosis with tylosis Hall-Riggs MOMO Ackerman 8 X-linked intellectual disability - dysmorphism cerebral atrophy Fountain Kallmann - heart disease CHIME oxoprolinase 8 Autosomal dominant familial hematuria - retinal arteriolar tortuosity - contractures ALG8-CDG MEHMO X-linked intellectual disability, Abidi type X-linked intellectual disability, Vitale type Leukoencephalopathy-ataxia-hypodontiahypomyelination Lethal polymalformative, Boissel type Acrocephalopolydactyly 8 Microcornea - posterior megalolenticonus persistent fetal vasculature - coloboma Pigmented paravenous retinochoroidal atrophy Parietal foramina with cleidocranial dysplasia 8 Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March

33 Lelis Brain calcification, Rajab type Osteopetrosis - hypogammaglobulinemia 8 Amelogenesis imperfecta-gingival hyperplasia Hermansky-Pudlak with neutropenia 8 Sodium channelopathy-related small fiber neuropathy 8 Porencephaly-microcephaly-bilateral congenital cataract Short stature due to GHSR 8 Mitochondrial hypertrophic cardiomyopathy with lactic acidosis due to MTO Sinoatrial node dysfunction and deafness 8 Mendelian susceptibility to mycobacterial diseases due to partial STAT1 Autosomal dominant Charcot-Marie-Tooth disease type 2Q Autosomal recessive limb-girdle muscular dystrophy type 2U Xq27.3q28 duplication NK-cell enteropathy 8 Premature aging appearance-developmental delay-cardiac arrhythmia Distal monosomy 12p 8 Autosomal recessive limb-girdle muscular dystrophy type 2P 8 Joubert with Jeune asphyxiating thoracic dystrophy 8 Alacrimia-choreoathetosis-liver dysfunction Familial median cleft of the upper and lower lips Silver-Russell due to a point mutation 8 Brain dopamine-serotonin vesicular transport disease Digital anomalies - intellectual disability - short stature Autosomal dominant intermediate Charcot-Marie Tooth disease type F X-linked Charcot-Marie-Tooth disease type 6 8 Autism spectrum disorder-epilepsy-arthrogryposis Severe combined immuno due to CTPS Lethal neonatal spasticity-epileptic encephalopathy Woolly hair-palmoplantar keratoderma Distal anoctaminopathy p25.3 microdeletion GCGR-related hyperglucagonemia 8 0 Ocular albinism with late-onset sensorineural deafness Acro-renal-mandibular Mitochondrial myopathy and sideroblastic anemia X-linked mandibulofacial dysostosis Bone dysplasia, lethal Holmgren type Retinal degeneration - nanophthalmos - glaucoma 7 Primary hypergonadotropic hypogonadism partial alopecia Gorlin-Chaudhry-Moss 7 Möbius - axonal neuropathy hypogonadotropic hypogonadism Stern-Lubinsky-Durrie Retinohepatoendocrinologic 7 Severe X-linked intellectual disability, Gustavson 3078 type Oliver 7 Torticollis - keloids - cryptorchidism - renal 3341 dysplasia Ehlers-Danlos, dermatosparaxis type Gamma-glutamyl transpeptidase Dihydropyrimidinuria Familial multiple fibrofolliculoma 7 Woolly hair-palmoplantar keratoderma-dilated cardiomyopathy CEDNIK Obesity due to pro-opiomelanocortin MPDU1-CDG Grange Spondylometaphyseal dysplasia, Schmidt type 7 X-linked neurodegenerative, Bertini type 7 Congenital malabsorptive diarrhea due to paucity of enteroendocrine cells Brachydactyly type A q11.2 microduplication X-linked Charcot-Marie-Tooth disease type Episodic ataxia type Virus-associated trichodysplasia spinulosa 7 Patent ductus arteriosus - bicuspid aortic valve hand anomalies Autosomal dominant striatal neurodegeneration Progressive cerebello-cerebral atrophy Paternal 14q32.2 hypomethylation CK p21 microdeletion X-linked intellectual disability, Van Esch type 7 X-linked intellectual disability - craniofacioskeletal UV-sensitive Episodic ataxia type 7 7 Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March

34 Deficiency in anterior pituitary function-variable immuno 7 Progeroid and marfanoid aspect-lipodystrophy Combined immuno due to STK Severe neonatal hypotonia-seizuresencephalopathy due to 5q microdeletion 7 X-linked immuno with magnesium defect, Epstein-Barr virus infection and neoplasia Autosomal recessive frontotemporal pachygyria 7 Microcephalic primordial dwarfism due to ZNF Hendra virus infection p13 microduplication q11.2 microduplication MRCS 7 Autosomal semi-dominant severe lipodystrophic laminopathy 7 Skin fragility-woolly hair-palmoplantar keratoderma q27.3 microdeletion 7 Intellectual disability-coarse face-macrocephalycerebellar hypotrophy Intellectual disability-facial dysmorphism due to SETD5 haploinsufficiency 7 Multisystemic smooth muscle dysfunction Autosomal recessive spastic paraplegia type MAN1B1-CDG 7 Intellectual disability-seizures-macrocephalyobesity Severe motor and intellectual disabilitiessensorineural deafness-dystonia Ataxia-intellectual disability-oculomotor apraxiacerebellar cysts Congenital neutropenia-myelofibrosisnephromegaly High myopia-sensorineural deafness p13.13 microdeletion 7 Autosomal recessive congenital cerebellar ataxia due to GRID Autism spectrum disorder due to AUTS2 7 Focal epilepsy-intellectual disability-cerebrocerebellar malformation Familial infantile myoclonic epilepsy Roifman Temple-Baraitser PDE4D haploinsufficiency 7 Familial atrial tachyarrhythmia-infra-hisian cardiac conduction disease Autosomal dominant Charcot-Marie-Tooth disease type 2 due to VCP mutation Primary immuno due to STAT Stormorken-Sjaastad-Langslet Epilepsy telangiectasia PAGOD 6 Thumb stiffness - brachydactyly - intellectual 1078 disability Recessive aplasia cutis congenita of limbs 6 Hidrotic ectodermal dysplasia, Christianson-Fourie type 1786 Acrofacial dysostosis, Catania type 6 Cutis gyrata - acanthosis nigricans craniosynostosis Isotretinoin-like Ramos-Arroyo 6 Hypogonadotropic hypogonadism - frontoparietal 2230 alopecia 6 Blepharophimosis - ptosis - esotropia - syndactyly short stature 2117 Hartsfield-Bixler-Demyer Paraplegia - intellectual disability - hyperkeratosis Keratosis follicularis - dwarfism - cerebral atrophy Spasticity - intellectual disability - X-linked epilepsy 6 X-linked intellectual disability - psychosis macroorchidism Polysyndactyly - cardiac malformation W Deafness - enamel hypoplasia - nail defects 6 Symphalangism with multiple anomalies of hands 3246 and feet Short fifth metacarpals - insulin resistance 6 Megalencephaly - polymicrogyria - postaxial polydactyly - hydrocephalus Eiken X-linked intellectual disability, Zorick type X-linked intellectual disability, Armfield type Carpenter-Waziri Autosomal recessive spastic paraplegia type Spinocerebellar ataxia type Ehlers-Danlos, cardiac valvular type 6 Severe combined immuno due to CORO1A RFT1-CDG Paternal 14q32.2 microdeletion Maternal 14q32.2 microdeletion 6 Autosomal recessive spastic ataxia - optic atrophy dysarthria p13.12 microdeletion 6 Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March

35 Autosomal recessive limb-girdle muscular dystrophy type 2Q Ectodermal dysplasia - syndactyly 6 Syndactyly - telecanthus - anogenital and renal malformations Cold-induced sweating 6 Ehlers-Danlos, spondylocheirodysplastic type 46,XY gonadal dysgenesis - motor and sensory neuropathy CLAPO Primary CD q22.1 microdeletion Endocrine-cerebro-osteodysplasia 6 Ehlers-Danlos, kyphoscoliotic and 179 deafness type Autosomal dominant aplasia and myelodysplasia p12.1 microdeletion 6 Combined immuno due to ORAI Pontocerebellar hypoplasia type 8 6 Progressive external ophthalmoplegia - myopathy emaciation Hermansky-Pudlak type 8 6 Fatal multiple mitochondrial dysfunction type Optic atrophy-intellectual disability Prader-Willi due to point mutation 6 Acute infantile liver failure-multisystemic involvement 6 Leukoencephalopathy with mild cerebellar ataxia and white matter edema 6 Severe neurodegenerative with lipodystrophy 6 Nail and teeth abnormalities-marginal palmoplantar keratoderma-oral hyperpigmentation Neonatal scleroderma 6 Autoimmune hemolytic anemia-autoimmune thrombocytopenia-primary immuno 6 Severe intellectual disability-hypotoniastrabismus-coarse face-planovalgus Contractures-developmental delay-pierre Robin Achalasia - microcephaly 5 5 Alopecia-contractures-dwarfism-intellectual disability 5 Choanal atresia-hearing loss-cardiac defectscraniofacial dysmorphism Anonychia - microcephaly Aphalangy - syndactyly - microcephaly Odontomicronychial dysplasia Dermatoosteolysis, Kirghizian type Acro-fronto-facio-nasal dysostosis Craniodigital - intellectual disability Dacryocystitis - osteopoikilosis Craniosynostosis - dysmorphism - brachydactyly Glaucoma - sleep apnea German Cystic hamartoma of lung and kidney Oculo-palato-cerebral 5 Nephrosis - deafness - urinary tract - digital 2669 malformations Nephropathy-deafness-hyperparathyroidism X-linked immunoneurologic disorder Mononen-Karnes-Senac Mikati-Najjar-Sahli Mesomelia-synostoses Kousseff Sillence Sakati-Nyhan 5 Intellectual disability - balding - patella luxation acromicria 5 3 Pyknoachondrogenesis Paraplegia - brachydactyly - cone-shaped epiphysis 5 Fallot complex - intellectual disability - growth 3304 delay 5 Cholestasis-pigmentary retinopathy-cleft palate Fine-Lubinsky 5 Arachnodactyly - abnormal ossification intellectual disability Acute bilateral depigmentation of the iris Beta-ureidopropionase 5 Growth delay due to insulin-like growth factor type Branchiogenic deafness CAMOS Bradyopsia Congenital bile acid synthesis defect type Deafness - hypogonadism 5 Localized lichen myxedematosus with monoclonal gammopathy or systemic symptoms Acanthosis nigricans - Insulin resistance - muscle cramps - acral enlargement 5 Lissencephaly type 3 - familial fetal akinesia sequence Lymphedema - cerebral arteriovenous anomaly Palmoplantar keratoderma - XX sex reversal - 5 Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March

36 predisposition to squamous cell carcinoma Astley-Kendall dysplasia 5 X-linked intellectual disability - cubitus valgus dysmorphism HSD10 disease, atypical type X-linked spinocerebellar ataxia type BRESEK Persistent placoid maculopathy Humero-ulnar synostosis Renier-Gabreels-Jasper Charcot-Marie-Tooth disease type 4J Frank-Ter Haar 5 Microcephaly - facio-cardio-skeletal, Hadziselimovic type Inherited congenital spastic tetraplegia 5 Frontonasal dysplasia with alopecia and genital anomaly Late-onset focal dermal elastosis Ptosis - syndactyly - learning difficulties 5 Recurrent infections - inflammatory due to zinc metabolism disorder ANE Cernunnos-XLF Spondyloepimetaphyseal dysplasia - hypotrichosis 5 Autosomal recessive lower motor neuron disease with childhood onset EAST 5 Hypoinsulinemic hypoglycemia and body hemihypertrophy 5 Childhood encephalopathy due to thiamine pyrophosphokinase Pre-Descemet corneal dystrophy 5 Multiple congenital anomalies-hypotonia-seizures type Onychocytic matricoma Follicular cholangitis and pancreatitis 5 Congenital cataract-hearing loss-severe 313 developmental delay Craniofacial dysplasia-osteopenia TMEM165-CDG Variant ABeta2M amyloidosis 5 Combined oxidative phosphorylation defect type Autosomal recessive mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR2 5 Beta-propeller protein-associated neurodegeneration 5 Methylmalonic aciduria due to transcobalamin receptor defect 5 Familial omphalocele with facial dysmorphism 5 Severe neonatal lactic acidosis due to NFS1-ISD complex 5 Infantile cerebral and cerebellar atrophy with postnatal progressive microcephaly p31p32 microdeletion Autosomal recessive isolated optic atrophy Pontocerebellar hypoplasia type 9 5 Combined oxidative phosphorylation defect type X-linked parkinsonism-spasticity LMNA-related cardiocutaneous progeria 5 Intellectual disability-hyperkinetic movementtruncal ataxia Cryptosporidiosis - chronic cholangitis - liver disease Progressive myoclonic epilepsy with dystonia 5 Autoimmune enteropathy and endocrinopathysusceptibility to chronic infections Spinocerebellar ataxia type q22.2q22.3 microdeletion 5 Juvenile-onset diabetes mellitus-central and peripheral neurodegeneration 5 Craniosynostosis - Dandy-Walker malformation hydrocephalus Arrhinia - choanal atresia - microphthalmia Central bilateral macrogyria Abruzzo-Erickson Metaphyseal acroscyphodysplasia Distal limb deficiencies - micrognathia Bonnemann-Meinecke-Reich Anophthalmia plus 4 Aortic arch anomaly - peculiar facies - intellectual 1110 disability Aplasia cutis - myopia Ectodermal dysplasia, Berlin type Hidrotic ectodermal dysplasia, Halal type Hypomandibular faciocranial dysostosis Arterial dissection - lentiginosis Coxoauricular Choroideremia - deafness - obesity 4 Ichthyosis - alopecia - eclabion - ectropion intellectual disability Hirschsprung disease - type D brachydactyly 4 Malignant hyperthermia - arthrogryposis torticollis Cole-Carpenter 4 Diaphragmatic defect - limb - skull 2141 defect 4 Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March

37 1973 Faciocardiorenal 4 Cleft lip/palate - intestinal malrotation - 1 cardiopathy Odontotrichomelic Neuroectodermal-endocrine Myoclonus-cerebellar ataxia-deafness 4 Leukoencephalopathy-palmoplantar keratoderma Kapur-Toriello 4 Intellectual disability - dysmorphism hypogonadism - diabetes mellitus 3052 X-linked intellectual disability - seizures - psoriasis 4 Non-eruption of teeth - maxillary hypoplasia genu valgum 2946 Brachydactyly - long thumb Short stature - webbed neck - heart disease Orofaciodigital type Spastic paraplegia - nephritis - deafness Homocarnosinosis Trichoodontoonychial dysplasia Ectopia lentis - chorioretinal dystrophy - myopia Familial caudal dysgenesis Lethal recessive chondrodysplasia Scott Hypotrichosis-lymphedema-telangiectasia-renal defect 4 Autosomal dominant multiple pterygium Permanent neonatal diabetes mellitus - pancreatic and cerebellar agenesis Benign exophthalmos Lathosterolosis MGAT2-CDG Sparse hair - short stature - skin anomalies 4 Primary immuno with natural-killer cell and adrenal insufficiency Simpson-Golabi-Behmel type Odontoleukodystrophy DK1-CDG Ichthyosis-hypotrichosis Pelviscapular dysplasia 4 Neurodegeneration due to 3-hydroxyisobutyryl CoA hydrolase 4 Primary immuno due to p X-linked intellectual disability - corpus callosum agenesis - spastic quadriparesis 4 X-linked intellectual disability - hypogonadism ichthyosis - obesity - short stature X-linked intellectual disability, Stoll type X-linked intellectual disability, Stevenson type X-linked intellectual disability, Seemanova type 4 Myopathy due to calsequestrin and SERCA protein overload 4 Leukoencephalopathy - metaphyseal chondrodysplasia 4 Microcephalic osteodysplastic dysplasia, Saul Wilson type Endosteal sclerosis - cerebellar hypoplasia Facial onset sensory and motor neuronopathy 4 Severe achondroplasia - developmental delay acanthosis nigricans 4 X-linked intellectual disability, Miles-Carpenter type X-linked intellectual disability, Schimke type 4 Spondylocostal dysostosis - anal and genitourinary malformations q14 microdeletion q24 microdeletion Hamel cerebro-palato-cardiac Syndactyly type Spondyloepimetaphyseal dysplasia, Shohat type 4 Hereditary sensory and autonomic neuropathy with deafness and global delay Autism - facial port-wine stain 4 Progressive demyelinating neuropathy with bilateral striatal necrosis 4 Hereditary hypotrichosis with recurrent skin vesicles Congenital lethal myopathy, Compton-North type 4 Pulmonary fibrosis - hepatic hyperplasia - bone marrow hypoplasia 4 Severe early-onset axonal neuropathy due to NEFL q12 microduplication Elastoderma 4 Cutis laxa with severe pulmonary, gastrointestinal and urinary anomalies Juvenile primary lateral sclerosis 4 Glaucoma secondary to spherophakia/ectopia lentis and megalocornea 4 Infantile onset panniculitis with uveitis and systemic granulomatosis 4 Microphthalmia - retinitis pigmentosa foveoschisis - optic disc drusen q31 microdeletion q25 microdeletion Autosomal recessive Stickler Polymicrogyria with optic nerve hypoplasia 4 Ectodermal dysplasia - cutaneous syndactyly Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March

38 FTH1-related iron overload Lethal acantholytic epidermolysis bullosa Spondyloepiphyseal dysplasia, Nishimura type Spondyloepiphyseal dysplasia, MacDermot type Spondyloepiphyseal dysplasia, Cantu type X-linked intellectual disability, Cilliers type Bilateral microtia - deafness - cleft palate RHYNS Multiple epiphyseal dysplasia, Al-Gazali type 4 Microcephaly - polymicrogyria - corpus callosum agenesis 4 Craniosynostosis - hydrocephalus - Arnold-Chiari malformation type I - radioulnar synostosis Blindness-scoliosis-arachnodactyly Urocanic aciduria Episodic ataxia type Pancreatic insufficiency - anemia - hyperostosis 4 Lethal occipital encephalocele-skeletal dysplasia Congenital dyserythropoietic anemia type IV 4 Hypogonadotropic hypogonadism-severe microcephaly-sensorineural hearing lossdysmorphism 4 Painful orbital and systemic neurofibromasmarfanoid habitus FADD-related immuno p13 microdeletion Jawad 4 Hereditary sensory and autonomic neuropathy type FGFR2-related bent bone dysplasia Atypical dentin dysplasia due to SMOC Parkinsonism due to ATP13A p13 microdeletion 4 X-linked mendelian susceptibility to mycobacterial diseases due to IKBKG Blepharophimosis-intellectual disability due to UBE3B Benign Samaritan congenital myopathy 4 Mitochondrial DNA deletion with progressive myopathy 4 Microcephaly-cerebellar hypoplasia-cardiac conduction defect Limbic encephalitis with DPP6 antibodies Distal 7q11.23 microduplication q14 microdeletion 4 Infantile spams - psychomotor retardation progressive brain atrophy - basal ganglia disease q22q23 microdeletion Severe combined immuno due to LCK 4 Hereditary sensorimotor neuropathy with hyperelastic skin 4 Chondrodysplasia with joint dislocations, gpapp type Warsaw breakage Autosomal recessive nail dysplasia Pontocerebellar hypoplasia type 7 4 Periodic paralysis with transient compartment-like Severe combined immuno due to IKK Short stature-auditory canal atresia-mandibular hypoplasia-skeletal anomalies 4 Diffuse cerebral and cerebellar atrophy-intractable seizures-progressive microcephaly AHDC1-related intellectual disability-obstructive sleep apnea-mild dysmorphism 4 Autosomal recessive spondylometaphyseal dysplasia, Mégarbané type 4 Severe intellectual disability-progressive spastic diplegia Female infertility due to zona pellucida defect 4 Hyperammonemic encephalopathy due to carbonic anhydrase VA Autosomal recessive spastic paraplegia type Autosomal recessive spastic paraplegia type Autosomal recessive spastic paraplegia type Epimetaphyseal skeletal dysplasia Prader-Willi-like due to point mutation 4 Sacral agenesis-abnormal ossification of the vertebral bodies-persistent notochordal canal 4 Microcephaly-thin corpus callosum-intellectual disability CADDS 4 Cardiac anomalies-developmental delay-facial dysmorphism 4 Severe intellectual disability-poor languagestrabismus-grimacing face-long fingers Mandibular hypoplasia-deafness-progeroid Intellectual disability-seizures-hypotoniaophthalmologic-skeletal anomalies Autosomal recessive cerebral atrophy 4 Ichthyosis-short stature-brachydactylymicrospherophakia Koolen-De Vries due to a point mutation 4 Short ulna - dysmorphism - hypotonia - intellectual disability SLC35A2-CDG q26q27 microdeletion 4 Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March

39 Developmental delay-microcephaly-facial dysmorphism, Hutterite type 4 Severe feeding difficulties - failure to thrive microcephaly due to ASXL3 4 Cobblestone lissencephaly without muscular or ocular involvement CLN13 disease 4 Progressive retinal dystrophy due to retinol transport defect 4 Autosomal recessive severe congenital neutropenia due to CSF3R 4 PCNA-related progressive neurodegenerative photosensitivy Progressive myoclonic epilepsy type 8 4 Lethal fetal brain malformation-duodenal atresiabilateral renal hypoplasia Peeling skin-leukonuchia-acral punctate keratosescheilitis-knuckle pads Mandibulofacial dysostosis with alopecia Distal myopathy with anterior tibial onset 4 Periodic fever-infantile enterocolitisautoinflammatory RARS-related autosomal recessive hypomyelinating leukodystrophy Ermine phenotype 3 Congenital osteogenesis imperfecta - microcephaly cataracts Disorder of sex development - intellectual 2983 disability Blepharoptosis - myopia - ectopia lentis 3 Camptodactyly - fibrous tissue hyperplasia skeletal dysplasia Heart-hand type Branchio-skeleto-genital Autosomal recessive amelia 3 Aniridia - ptosis - intellectual disability - familial 1067 obesity AREDYLD Aniridia-absent patella 3 Aphalangy - hemivertebrae - urogenital-intestinal 1112 dysgenesis 3 Aplasia cutis congenita - intestinal 1116 lymphangiectasia 3 Hypohidrotic ectodermal dysplasia hypothyroidism - ciliary dyskinesia 3 Intellectual disability - hypoplastic corpus callosum preauricular tag 1529 Craniofacial-deafness-hand Craniofrontonasal dysplasia - Poland anomaly 3 Hair defect - photosensitivity - intellectual 1408 disability Cortical blindness - intellectual disability - 3 polydactyly 2153 Hirschsprung disease-nail hypoplasia-dysmorphism Cervical hypertrichosis - peripheral neuropathy 3 Posterior fusion of lumbosacral vertebrae blepharoptosis Multinodular goiter - cystic kidney - polydactyly 3 Glaucoma - ectopia - microspherophakia - stiff 2084 joints - short stature Lethal faciocardiomelic dysplasia 3 Facial dysmorphism - macrocephaly - myopia Dandy-Walker malformation Lethal omphalocele-cleft palate Orofaciodigital type Oculoosteocutaneous Nail-patella-like renal disease N Microcephaly - cardiomyopathy Microcephaly - cleft palate 3 Microcephaly - cardiac defect - lung 2516 malsegmentation Czeizel-Losonci 3 Hypergonadotropic hypogonadism - cataract Lowry-MacLean Eyebrow duplication - syndactyly Summitt Autosomal dominant vitreoretinochoroidopathy Revesz Qazi-Markouizos 3 Retinal ischemic - digestive tract small 3018 vessel hyalinosis - diffuse cerebral calcifications 3 Absent thumb-short stature-immuno Cutaneous photosensitivity - lethal colitis 3 Osteoporosis - oculocutaneous hypopigmentation Thymic-renal-anal-lung dysplasia Absent tibia - polydactyly - arachnoid cyst Cardiospondylocarpofacial Ulbright-Hodes 3 Trigonocephaly - short stature - developmental 3369 delay 3 Short stature - intellectual disability - eye 2649 anomalies - cleft lip/palate Microcephaly - brachydactyly - kyphoscoliosis 3 Anophthalmia - megalocornea - cardiopathy skeletal anomalies Cataract - deafness - hypogonadism 3 Müllerian derivatives - lymphangiectasia polydactyly 3 Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March

40 Arachnodactyly - intellectual disability dysmorphism 3 Short stature due to growth hormone qualitative 629 anomaly Anonychia with flexural pigmentation 3 Sensorineural hearing loss - early graying essential tremor Goodman 3 Global developmental delay - osteopenia ectodermal defect Lipodystrophy - intellectual disability - deafness Craniosynostosis - intracranial calcifications Agammaglobulinemia-microcephalycraniosynostosis-severe dermatitis ALG9-CDG GCS1-CDG 3 Seizures - intellectual disability due to hydroxylysinuria 3 Osteosclerosis - ichthyosis - premature ovarian failure Microphthalmia - brain atrophy Cloverleaf skull - multiple congenital anomalies 3 Hemolytic anemia due to glutathione reductase X-linked intellectual disability, Shrimpton type 3 Deafness - intellectual disability, Martin-Probst type DPAGT1-CDG 3 Psychomotor retardation due to S adenosylhomocysteine hydrolase Lymphedema - atrial septal defects - facial changes Microcytic anemia with liver iron overload X-linked intellectual disability, Wittwer type 3 X-linked intellectual disability hypogammaglobulinemia - progressive neurological deterioration 3 X-linked intellectual disability - precocious puberty obesity X-linked intellectual disability, Wilson type Holmes-Gang Chudley-Lowry-Hoar X-linked intellectual disability, Golabi-Ito-Hall type SERKAL 3 Microcephaly - intellectual disability - phalangeal and neurological anomalies 3 Hypotonia with lactic acidemia and hyperammonemia Congenital enterocyte heparan sulfate 3 Intractable diarrhea - choanal atresia - eye anomalies Glycogen storage disease due to muscle and heart 3 glycogen synthase Neutral lipid storage myopathy RIN2 3 Neurodegenerative due to cerebral folate transport Zechi-Ceide Ehlers-Danlos, vascular-like type 3 Ptosis - upper ocular movement limitation absence of lacrimal punctum Maternal 14q32.2 hypermethylation p11.2 deletion Spondyloepiphyseal dysplasia tarda, Kohn type X-linked intellectual disability, Kroes type Pontocerebellar hypoplasia type Suarez-Stickler Spondyloepimetaphyseal dysplasia, Bieganski type Spondylometaphyseal dysplasia, Golden type Axial spondylometaphyseal dysplasia 3 Hemorrhagic disease due to alpha-1-antitrypsin Pittsburgh mutation Intellectual disability - cataracts - kyphosis Spondyloepimetaphyseal dysplasia, aggrecan type 3 Autosomal recessive limb-girdle muscular dystrophy type 2M Familial infantile gigantism 3 Severe congenital hypochromic anemia with 298 ringed sideroblasts 3 Nephrotic -deafness-pretibial 333 epidermolysis bullosa 3 Primary microcephaly-epilepsy-permanent neonatal diabetes Optic nerve edema-splenomegaly 3 Congenital nephrotic -interstitial lung disease-epidermolysis bullosa 3 Frontonasal dysplasia-severe microphthalmiasevere facial clefting Xq12-q13.3 duplication 3 Young adult-onset distal hereditary motor neuropathy 3 Autosomal recessive leukoencephalopathy with ischemic stroke-retinitis pigmentosa 3 Hypertrophic cardiomyopathy and renal tubular disease due to mitochondrial DNA mutation Early-onset Lafora body disease 3 Mendelian susceptibility to mycobacterial diseases due to complete ISG15 Autoinflammatory with pyogenic bacterial infection and amylopectinosis 3 Congenital muscular dystrophy with intellectual disability and severe epilepsy JMP 3 Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March

41 Congenital cataract - progressive muscular 354 hypotonia - hearing loss - developmental delay q11.2 microdeletion q12 microdeletion p12.3 microdeletion COG1-CDG Progressive myoclonic epilepsy type PLIN1-related familial partial lipodystrophy Occipital pachygyria and polymicrogyria q12.3 microdeletion 3 Early onset epileptic encephalopathy-cortical blindness-intellectual disability-facial dysmorphism 3 Epidermolysis bullosa simplex due to exophilin Autosomal recessive cerebellar ataxia-epilepsyintellectual disability due to TUD Progressive myoclonic epilepsy type 5 3 FBLN1-related developmental delay-central nervous system anomaly-syndactyly Lipoic acid synthetase Spasticity-ataxia-gait anomalies q24.1q24.3 microdeletion Autosomal recessive spastic paraplegia type 59 3 Severe intellectual disability-progressive postnatal microcephaly- midline stereotypic hand 3 movements Ferro-cerebro-cutaneous 3 Combined immuno due to MALT Severe dermatitis-multiple allergies-metabolic wasting Medich giant platelet SCALP 3 Intellectual disability-facial dysmorphism-hand anomalies 3 Acroosteolysis-keloid-like lesions-premature aging Intellectual disability-feeding difficultiesdevelopmental delay-microcephaly Autosomal recessive intermediate Charcot-Marie Tooth disease type C 3 Autosomal recessive limb-girdle muscular dystrophy type 2S Charcot-Marie-Tooth disease type 4B3 3 Intellectual disability - hypotonia - spasticity sleep disorder 3 Mitochondrial DNA depletion, hepatocerebrorenal form 3 Fetal akinesia-cerebral and retinal hemorrhage Early-onset progressive neurodegeneration blindness - ataxia - spasticity Salt-and-pepper 3 Severe intellectual disability-short staturebehavioral troubles-facial dysmorphism Infantile-onset mesial temporal lobe epilepsy with severe cognitive regression SURF1-related Charcot-Marie-Tooth disease type 4 3 Hereditary sensory and autonomic neuropathy type 7 3 Primary microcephaly-mild intellectual disabilityyoung-onset diabetes HSD10 disease, neonatal type Feingold type Bleeding disorder due to CalDAG-GEFI Cono-spondylar dysplasia 3 Muscular dystrophy with progressive weakness, distal contractures and rigid spine 3 Autosomal recessive intermediate Charcot-Marie Tooth disease type D 3 Retinitis pigmentosa-juvenile cataract-short stature-intellectual disability 3 Microcephaly-complex motor and sensory axonal neuropathy Neonatal dermatomyositis ,XX ovarian dysgenesis-short stature 3 Combined oxidative phosphorylation type 24 3 Cognitive impairment-coarse facies-heart defectsobesity-pulmonary involvement-short stature skeletal dysplasia 3 Cataract-growth hormone -sensory neuropathy-sensorineural hearing loss-skeletal dysplasia 3 Colobomatous optic disc-macular atrophychorioretinopathy X-linked microcephaly-growth retardationprognathism-cryptorchidism Progeroid features-hepatocellular carcinoma predisposition 3 Severe intellectual disability-epilepsy-cataract due to fatty acyl-coa reductase 1 3 Autosomal recessive primary immuno with defective spontaneous natural killer cell cytotoxicity 3 Multiple epiphyseal dysplasia, with severe proximal femoral dysplasia 3 Osteogenesis imperfecta - retinopathy - seizures intellectual disability Cooper-Jabs Gonadal dysgenesis, XY type - associated anomalies 2 Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March

42 1046 Lethal hemolytic anemia - genital anomalies 2 Hypogonadism - mitral valve prolapse - intellectual disability Mitochondrial DNA depletion, 1933 encephalomyopathic form with methylmalonic aciduria Hennekam-Beemer Chondrodysplasia - disorder of sex development 2 Multiple sclerosis - ichthyosis - factor VIII Epilepsy - microcephaly - skeletal dysplasia Heart defects - limb shortening Acrocraniofacial dysostosis Bangstad Beemer-Ertbruggen Camptodactyly, Guadalajara type 2 2 Brachytelephalangy - dysmorphism - Kallmann Amaurosis-hypertrichosis Aniridia-intellectual disability Aniridia - renal agenesis - psychomotor retardation 2 3 Scalp defects - postaxial polydactyly 2 Alopecia-intellectual disability-hypergonadotropic hypogonadism 1659 Dermatoleukodystrophy Ectodermal dysplasia - blindness 2 Dandy-Walker malformation - postaxial 1566 polydactyly Dahlberg-Borer-Newcomer 2 Cryptomicrotia - brachydactyly - excess fingertip 1547 arch Craniosynostosis - fibular aplasia Cataract - nephropathy - encephalopathy Cataract - ataxia - deafness 2 Contractures - ectodermal dysplasia - cleft 1484 lip/palate Cleidorhizomelic Choroidal atrophy - alopecia 2 Hypogonadotropic hypogonadism - retinitis 2235 pigmentosa 2 Male hypergonadotropic hypogonadism intellectual disability - skeletal anomalies 2 Hyposmia - nasal and ocular hypoplasia hypogonadotropic hypogonadism Ulna hypoplasia - intellectual disability Hypotrichosis-intellectual disability, Lopes type Ichthyosis - oral and digital anomalies Congenital ichthyosis - microcephalus - tetraplegia Ichthyosis - hepatosplenomegaly - cerebellar degeneration 2 Dysmorphism - short stature - deafness - disorder 2282 of sex development Hirschsprung disease - deafness - polydactyly 2 Microcephaly - glomerulonephritis - marfanoid 2172 habitus Hydrocephaly - tall stature - joint laxity HEC Cleft lip - retinopathy 2 Alar cartilages hypoplasia-coloboma-telecanthus Cleft palate - stapes fixation - oligodontia Gingival fibromatosis - facial dysmorphism Oculotrichodysplasia Microcephaly - albinism - digital anomalies Microbrachycephaly - ptosis - cleft lip Lichstenstein Lethal Kniest-like dysplasia Kaler-Garrity-Stern Corneal-cerebellar Stimmler 2 Deaf blind hypopigmentation, Yemenite type 3105 Robinow-like Say-Barber-Miller SCARF 2 Spastic tetraplegia - retinitis pigmentosa intellectual disability 2 46,XX disorder of sex development - skeletal 2975 anomalies 2 Pterygium colli - intellectual disability - digital 2988 anomalies Pseudoprogeria Pierre Robin - faciodigital anomaly Short stature, Brussels type PHAVER Pilodental dysplasia - refractive errors PARC Spastic paraplegia - precocious puberty Syngnathia multiple anomalies Teebi-Shaltout Thrombocytopenia - Robin sequence Thyrocerebrorenal 2 Deafness - genital anomalies - metacarpal and 3224 metatarsal synostosis Deafness - vitiligo - achalasia Trigonocephaly - broad thumbs Trigonocephaly - bifid nose - acral anomalies 2 3 Stoll-Alembik-Finck 2 Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March

43 3167 Siegler-Brewer-Carey Kozlowski-Brown-Hardwick 2 Microcephaly - seizures - intellectual disability heart disease 2 Osteochondrodysplatic nanism - deafness retinitis pigmentosa 2 Adult familial nephronophthisis - spastic 2666 quadriparesia Arthrogryposis - hyperkeratosis, lethal form Okamoto 2 Atherosclerosis - deafness - diabetes - epilepsy nephropathy Cleft palate - short stature - vertebral anomalies Macrocephaly - short stature - paraplegia X-linked intellectual disability - plagiocephaly Hydrocephalus - obesity - hypogonadism 2 Central nervous system calcification - deafness tubular acidosis - anemia 2 Anhidrotic ectodermal dysplasiaimmuno-osteopetrosis-lymphedema Congenital brain dysgenesis due to glutamine synthetase Tubular renal disease - cardiomyopathy 2 Ossification anomalies - psychomotor development delay 2 Spinal muscular atrophy - Dandy-Walker malformation - cataracts 2 Visceral neuropathy - brain anomalies - facial dysmorphism - developmental delay Auriculoocular anomalies - cleft lip 2 Dentinogenesis imperfecta - short stature - hearing loss - intellectual disability Zellweger-like without peroxisomal anomalies Duane anomaly - myopathy - scoliosis Talo-patello-scaphoid osteolysis Microlissencephaly - micromelia Braddock 2 Agenesis of the corpus callosum-intellectual disability-coloboma-micrognathia Acrofacial dysostosis, Kennedy-Teebi type Congenital bile acid synthesis defect type B4GALT1-CDG 2 Brain malformation - congenital heart disease postaxial polydactyly 2 Developmental malformations - deafness dystonia 2 Neonatal diabetes - congenital hypothyroidism congenital glaucoma - hepatic fibrosis - polycystic kidneys 2 Not NOTCH3-related small vessel disease of the brain 2 Auricular abnormalities - cleft lip with or without 77 cleft palate - ocular abnormalities 2 Osteopenia - myopia - hearing loss - intellectual disability - facial dysmorphism Cardiomyopathy - hypotonia - lactic acidosis Macular coloboma-cleft palate-hallux valgus 2 Obesity - colitis - hypothyroidism - cardiac hypertrophy - developmental delay Cardiomyopathy - renal anomalies 2 X-linked intellectual disability - acromegaly hyperactivity Lissencephaly type 3 - metacarpal bone dysplasia 2 Hypercoagulability due to glycosylphosphatidylinositol 2 X-linked intellectual disability - epilepsy progressive joint contractures - dysmorphism 2 Familial papillary thyroid carcinoma with renal papillary neoplasia COG8-CDG 2 Severe intellectual disability-epilepsy-anal anomalies-distal phalangeal hypoplasia Congenital panfollicular nevus 2 Microcephaly - digital anomalies - intellectual disability 2 Lung fibrosis - immuno - 46,XX gonadal dysgenesis Epithelio-exfoliative colitis - deafness 2 Resistance to thyrotropin-releasing hormone Univentricular heart with single atrio-ventricular valve Congenital insensitivity to pain with hyperhidrosis Atypical hypotonia - cystinuria Autosomal recessive lymphoproliferative disease 2 Severe X-linked mitochondrial encephalomyopathy 2 Late-onset localized junctional epidermolysis bullosa - intellectual disability 2 Autosomal recessive ataxia due to PEX Leukoencephalopathy - dystonia - motor neuropathy Hyperekplexia - epilepsy 2 Hypospadias - hypertelorism - coloboma and deafness 2 Hereditary cryohydrocytosis with reduced stomatin 2 Fatal mitochondrial disease due to combined oxidative phosphorylation Spondylometaphyseal dysplasia, A4 type 2 Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March

44 Brain demyelination due to methionine adenosyltransferase Immuno due to CD Metaphyseal chondrodysplasia, Kaitila type 2 Metaphyseal chondrodysplasia - retinitis pigmentosa 2 FASTKD2-related infantile mitochondrial encephalomyopathy 2 Spondyloepimetaphyseal dysplasia - abnormal dentition 2 Spondyloepimetaphyseal dysplasia, Geneviève type 2 Spondylometaphyseal dysplasia - bowed forearms facial dysmorphism Neutrophil immuno Thiamine-responsive encephalopathy Congenital myopathy, Paradas type Ketamine-induced biliary dilatation q31.1 microduplication Neonatal inflammatory skin and bowel disease Early-onset spastic ataxia-neuropathy Autosomal recessive spastic paraplegia type q23.1 microduplication 2 Contractures-webbed neck-micrognathiahypoplastic nipples p22.1 microduplication High bone mass osteogenesis imperfecta 2 Marfanoid habitus - inguinal hernia - advanced bone age CLN11 disease 2 Intellectual disability-hypotonia-brachycephalypyloric stenosis-cryptorchidism Autoinflammation-PLCG2-associated antibody immune dysregulation 2 Aphonia - deafness - retinal dystrophy - bifid halluces - intellectual disability 2 Muscular hypertrophy - hepatomegaly polyhydramnios 2 X-linked intellectual disability - cardiomegaly congestive heart failure Severe lateral tibial bowing with short stature 2 Multiple paragangliomas associated with polycythemia 2 T-cell immuno with epidermodysplasia verruciformis 2 Mendelian susceptibility to mycobacterial diseases due to partial IRF8 Autosomal dominant mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR2 2 Spondylocostal dysostosis - hypospadias intellectual disability 2 Congenital chronic diarrhea with protein-losing enteropathy 2 Intellectual disability - craniofacial dysmorphism cryptorchidism Hyperinsulinism due to HNF1A 2 Congenital ichthyosis-intellectual disability-spastic quadriplegia Paternal 20q13.2q13.3 microdeletion ,XXXYY COG4-CDG CHST3-related skeletal dysplasia Hyperinsulinism due to UCP Hyperbiliverdinemia ALG11-CDG Nestor-Guillermo progeria Familial Alzheimer-like prion disease Hermansky-Pudlak type Acral self-healing collodion baby COASY protein-associated neurodegeneration 2 Autosomal dominant Charcot-Marie-Tooth disease type 2U Hermansky-Pudlak type Cystic fibrosis - gastritis - megaloblastic anemia Dystonia-aphonia 2 Epidermolysis bullosa simplex due to BP Autosomal recessive cerebellar ataxia-epilepsyintellectual disability due to KIAA Global developmental delay-lung cystsovergrowth-wilms tumor Lipoyl transferase q31.1q31.3 microdeletion 2 Partial corpus callosum agenesis-cerebellar vermis hypoplasia with posterior fossa cysts Pancytopenia-developmental delay Autosomal recessive spastic paraplegia type Autosomal recessive spastic paraplegia type Autosomal recessive spastic paraplegia type Autosomal recessive spastic paraplegia type TCR-alpha-beta-positive T-cell Autosomal recessive spastic paraplegia type 58 2 Intellectual disability-obesity-prognathism-eye and skin anomalies Finger hyperphalangy-toe anomalies-severe pectus excavatum Methylmalonic acidemia with homocystinuria, type cblj Aldosterone-producing adenoma with seizures and neurological abnormalities Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March

45 Early infantile epileptic encephalopathy without suppression burst p21 microdeletion without cystinuria STT3A-CDG Angora hair nevus Spondyloepimetaphyseal dysplasia, Isidor type 2 Spondylometaphyseal dysplasia, Czarny-Ratajczak type p13.2 microdeletion 2 Autosomal recessive limb-girdle muscular dystrophy type 2T 2 Autosomal recessive limb-girdle muscular dystrophy type 2R 2 Severe combined immuno due to CARD11 2 Mandibulofacial dysostosis - macroblepharon macrostomia 2 Hypotonia-cerebral atrophy-hyperglycinemia Corneal intraepithelial dyskeratosis-palmoplantar hyperkeratosis-laryngeal dyskeratosis 2 Intellectual disability - obesity - brain malformations - facial dysmorphism 2 Infantile hypertrophic cardiomyopathy due to MRPL XYLT1-CDG 2 Muscle-eye-brain disease with bilateral multicystic leucodystrophy Fatal post-viral neurodegenerative disorder 2 Growth and developmental delay-hypotonia-vision impairment-lactic acidosis Growth retardation-mild developmental delaychronic hepatitis RIDDLE 2 Combined oxidative phosphorylation type 20 2 Autosomal recessive severe congenital neutropenia due to CXCR AApoAIV amyloidosis 2 Combined oxidative phosphorylation type Congenital myopathy with myasthenic-like onset 2 Microcephaly-short stature-intellectual disabilityfacial dysmorphism X-linked intellectual disability-limb spasticityretinal dystrophy-diabetes insipidus Autosomal dominant Charcot-Marie-Tooth disease type 2 due to TFG mutation Autosomal recessive spastic paraplegia type Neonatal autoimmune hemolytic anemia Isolated sedoheptulokinase Microcephalic primordial dwarfism-insulin 2 resistance Lethal fetal cerebrorenogenitourinary agenesis/hypoplasia LIPE-related familial partial lipodystrophy 2 Severe autosomal recessive macrothrombocytopenia 2 Progressive encephalopathy with leukodystrophy due to DECR L-ferritin Charcot-Marie-Tooth disease type 2T 2 Limb-girdle muscular dystrophy due to POMK Multiple epiphyseal dysplasia, with miniepiphyses ALG2-CDG 1 Case Glycogen storage disease due to muscle betaenolase Case Dimethylglycine dehydrogenase 1 Case SLC35A1-CDG 1 Case Autosomal recessive intermediate Charcot-Marie Tooth disease type B 1 Case AICA-ribosiduria 1 Case 536 DDOST-CDG 1 Case ALG13-CDG 1 Case 329 Hypotrichosis-deafness 1 Case Lethal encephalopathy due to mitochondrial and 350 peroxisomal fission defect 1 Case Transient neonatal multiple acyl-coa dehydrogenase 1 Case Glycogen storage disease due to glycogenin Case DPM3-CDG 1 Case Spinal muscular atrophy with respiratory distress type 2 1 Case Maternal riboflavin 1 Case Autosomal recessive spastic paraplegia type 60 1 Case Autosomal recessive spastic paraplegia type 68 1 Case Autosomal recessive spastic paraplegia type 71 1 Case Charcot-Marie-Tooth disease type 2R 1 Case STT3B-CDG 1 Case Oculocutaneous albinism type 6 1 Case SSR4-CDG 1 Case Ribose-5-P isomerase 1 Case COG2-CDG 1 Case Combined immuno due to OX Case CIDEC-related familial partial lipodystrophy 1 Case Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March

46 of published families of families Dent disease 1949 Benign familial neonatal epilepsy 1416 Familial calcium pyrophosphate deposition Dystrophic epidermolysis bullosa pruriginosa Spinocerebellar ataxia type 17 Autosomal dominant nocturnal frontal lobe epilepsy Pontocerebellar hypoplasia type Pseudohypoaldosteronism type Loeys-Dietz Nance-Horan 2526 Microcephaly - lymphedema - chorioretinopathy Huntington disease-like 2 46,XY disorder of sex development due to alpha-reductase Pontocerebellar hypoplasia type Pretibial dystrophic epidermolysis bullosa Spinocerebellar ataxia type Peeling skin type A Microphthalmia with limb anomalies Punctate palmoplantar keratoderma type X-linked intellectual disability, Najm type Immuno with factor I anomaly Autosomal recessive axonal neuropathy with neuromyotonia Glycogen storage disease due to phosphoglycerate kinase Camptodactyly-arthropathy-coxa-varapericarditis Apolipoprotein A-I Phosphoribosylpyrophosphate synthetase superactivity 3237 Multiple synostoses 30 of families Primary erythermalgia Hereditary combined of vitamin K dependent clotting factors Spinocerebellar ataxia type 31 MITF-related melanoma and renal cell carcinoma predisposition Peeling skin type B Lethal multiple pterygium Familial hyperthyroidism due to mutations in TSH receptor X-linked intellectual disability, Cabezas type Giant axonal neuropathy Acro-renal-ocular Dilated cardiomyopathy - hypergonadotropic hypogonadism Overhydrated hereditary stomatocytosis Familial platelet with predisposition to acute myelogenous leukemia Spinocerebellar ataxia type Carney-Stratakis 998 Autosomal dominant spastic paraplegia type Adult-onset autosomal dominant leukodystrophy Dehydrated hereditary stomatocytosis Dentin dysplasia type II Non-spherocytic hemolytic anemia due to hexokinase Infantile-onset ascending hereditary spastic paralysis Ichthyosis prematurity Fibronectin glomerulopathy 2950 Triphalangeal thumb - polysyndactyly X-linked myopathy with excessive autophagy X-linked distal arthrogryposis multiplex congenita X-linked intellectual disability - cerebellar hypoplasia Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March

47 of families Familial anetoderma Karyomegalic interstitial nephritis Smith-Fineman-Myers Charcot-Marie-Tooth disease type 4B Posterior amorphous corneal dystrophy KCNQ2-related epileptic encephalopathy Acheiropodia Brachydactyly-arterial hypertension Hereditary neurocutaneous angioma Tarsal-carpal coalition Familial isolated hypoparathyroidism Palmoplantar keratoderma-esophageal carcinoma Palmoplantar keratoderma-deafness Otodental VACTERL with hydrocephalus X-linked cone dysfunction with myopia 10 Syndromic X-linked intellectual disability due to JARID1C mutation Benign familial neonatal-infantile seizures 994 Autosomal dominant spastic paraplegia type Autosomal dominant spastic paraplegia type Autosomal dominant spastic paraplegia type Autosomal dominant spastic paraplegia type Autosomal dominant spastic paraplegia type Autosomal recessive spastic paraplegia type Autosomal recessive spastic paraplegia type Acral dystrophic epidermolysis bullosa Dystrophic epidermolysis bullosa, nails only of families Pontocerebellar hypoplasia type 4 Hereditary proximal myopathy with early respiratory failure Xeroderma pigmentosum complementation group B Autosomal recessive cerebellar ataxia due to STUB Hereditary vascular retinopathy ACys amyloidosis BNAR Cataract-microcornea Lethal osteosclerotic bone dysplasia Goldberg-Shprintzen megacolon 8 Autosomal recessive intermediate Charcot Marie-Tooth disease type A Isolated hereditary congenital facial paralysis EEM Temtamy Autosomal dominant spastic paraplegia type Familial hyperaldosteronism type III 7 Autosomal recessive systemic lupus 345 erythematosus Distal arthrogryposis type 5D Annular epidermolytic ichthyosis 7 Foveal hypoplasia-optic nerve decussation defect-anterior segment dysgenesis ALys amyloidosis Familial developmental dysphasia Ichthyosis hystrix of Curth-Macklin Epidermolysis bullosa simplex, Ogna type Cystoid macular dystrophy 6 Deafness with labyrinthine aplasia, microtia, and microdontia X-linked reticulate pigmentary disorder with systemic manifestations Stapes ankylosis with broad thumbs and toes Overgrowth - macrocephaly - facial dysmorphism 6 Mesoaxial synostotic syndactyly with phalangeal reduction Hypopigmentation-punctate palmoplantar keratoderma Atypical juvenile parkinsonism Hawkinsinuria Familial chondromalacia patellae Mesomelic dysplasia, Kantaputra type X-linked sideroblastic anemia and ataxia Distal symphalangism Trichodental 5 Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March

48 of families Intellectual disability-developmental delaycontractures Familial primary hypomagnesemia with normocalciuria and normocalcemia 5 Autosomal dominant limb-girdle muscular dystrophy type 1E 5 Autosomal dominant limb-girdle muscular dystrophy type 1D 5 Short stature - pituitary and cerebellar defects small sella turcica 5 Familial encephalopathy with neuroserpin inclusion bodies 5 X-linked hereditary sensory and autonomic neuropathy with deafness 5 Female restricted epilepsy with intellectual disability Congenital stromal corneal dystrophy 5 Autosomal dominant Charcot-Marie-Tooth disease type 2F Familial rhabdoid tumor Åland Islands eye disease 5 Autism-epilepsy due to branched chain ketoacid dehydrogenase kinase Ocular albinism with congenital sensorineural deafness Melorheostosis with osteopoikilosis X-linked osteoporosis with fractures 5 Colobomatous microphthalmia-rhizomelic dysplasia 5 Autoimmune interstitial lung disease-arthritis Patella aplasia/hypoplasia Brachydactyly - elbow wrist dysplasia IVIC Triphalangeal thumbs - brachyectrodactyly Paroxysmal extreme pain disorder Majeed Reducing body myopathy Spinocerebellar ataxia type Early-onset X-linked isolated optic atrophy 4 Progressive sensorineural hearing loss hypertrophic cardiomyopathy MEDNIK EDICT 4 Facial dysmorphism-lens dislocation-anterior segment abnormalities-spontaneous filtering blebs 4 AXIN2-related attenuated familial adenomatous polyposis 4 Hyperuricemia-pulmonary hypertension-renal failure-alkalosis 4 of families Spinocerebellar ataxia type Nebulin-related early-onset distal myopathy Blepharonasofacial malformation Dermato-cardio-skeletal, Borrone type Ankyloblepharon filiforme - imperforate anus 3 Hypertelorism - hypospadias - polysyndactyly Median nodule of the upper lip 3 Adducted thumbs-arthrogryposis, 2952 Christian type Cerebroretinal vasculopathy WT limb-blood 3 Gamma-aminobutyric acid transaminase Cataract-glaucoma 3 X-linked intellectual disability with isolated growth hormone 3 Thrombocytopenia with congenital dyserythropoietic anemia Autosomal dominant optic atrophy and cataract Congenital dyserythropoietic anemia type III Spinocerebellar ataxia type Pontocerebellar hypoplasia type 3 3 Autosomal recessive cerebellar ataxia - blindness deafness Deafness-infertility Autosomal recessive spastic paraplegia type 30 3 Autosomal dominant Charcot-Marie-Tooth disease type 2K Craniorhiny 3 PLCG2-associated antibody and 359 immune dysregulation X-linked non progressive cerebellar ataxia 3 Hereditary thrombocytosis with transverse limb defect Spinocerebellar ataxia type 35 3 Familial progressive hyper- and hypopigmentation 3 Autosomal dominant Charcot-Marie-Tooth disease type 2 with giant axons 3 Short stature-advanced bone age-early onset osteoarthritis Cerebellar-facial-dental 3 Maternally-inherited cardiomyopathy and 1349 hearing loss 2 Retinitis pigmentosa - intellectual disability deafness - hypogenitalism 2 Congenital absence/hypoplasia of fingers 973 excluding thumb, unilateral Bencze Auriculoosteodysplasia 2 Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March

49 of families 1187 Lethal ataxia with deafness and optic atrophy Bullous dystrophy, macular type Heart-hand type Skeletal dysplasia - intellectual disability 2 Familial isolated hypoparathyroidism due to 2239 agenesis of parathyroid gland Gingival fibromatosis - progressive deafness Joubert with orofaciodigital defect 2 Metaphyseal dysplasia - maxillary hypoplasia brachydacty Thickened earlobes - conductive deafness 2 Spastic paraplegia - glaucoma - intellectual 2818 disability Tietz 2 Autosomal dominant limb-girdle muscular 266 dystrophy type 1A HERNS 2 Autosomal dominant limb-girdle muscular dystrophy type 1G Hereditary painful callosities Episodic ataxia type X-linked Ehlers-Danlos North Carolina macular dystrophy Progressive bifocal chorioretinal atrophy 2 Alport -intellectual disability-midface hypoplasia-elliptocytosis X-linked intellectual disability, Siderius type Partington Brachydactyly-syndactyly, Zhao type Brachydactyly type A Microphthalmia with brain and digit anomalies Autosomal recessive spastic paraplegia type 39 2 Hereditary sensory and autonomic neuropathy type 1B Autosomal recessive spastic paraplegia type 27 2 Sensorineural deafness with dilated cardiomyopathy Oligodontia - cancer predisposition 2 Tall stature - scoliosis - macrodactyly of the great toes Spectrin-associated autosomal recessive cerebellar ataxia ITM2B amyloidosis Orofaciodigital type Albinism-deafness 1 Family 1876 Oculogastrointestinal muscular dystrophy 1 Family 1228 Banki 1 Family 1319 Camptobrachydactyly 1 Family 1144 Arthrogryposis-like hand anomaly - sensorineural 1 Family of families deafness Lipodystrophy due to peptidic growth factors Family Steroid dehydrogenase - dental 3196 anomalies 1 Family 1765 Dyschondrosteosis - nephritis 1 Family 1527 Craniosynostosis, Philadelphia type 1 Family Woolly hair - hypotrichosis - everted lower lip outstanding ears 1 Family 2186 Hydrocephalus - blue sclerae - nephropathy 1 Family 2709 Oculodental, Rutherfurd type 1 Family 2674 Cyprus facial-neuromusculoskeletal 1 Family 2391 Congenitally short costocoracoid ligament 1 Family 2999 Ptosis - strabismus - ectopic pupils 1 Family 2890 Pili torti - onychodysplasia 1 Family 2917 Polydactyly-myopia 1 Family 3408 Upington disease 1 Family 3417 Van den Bosch 1 Family 1246 Brachydactyly - nystagmus - cerebellar ataxia 1 Family Ulnar/fibula ray defect - brachydactyly 1 Family Autosomal dominant limb-girdle muscular dystrophy type 1F 1 Family Episodic ataxia type 3 1 Family Trichodysplasia - amelogenesis imperfecta 1 Family Ehlers-Danlos, fibronectinemic type 1 Family AKT2-related familial partial lipodystrophy 1 Family Spondyloepiphyseal dysplasia, Kimberley type 1 Family Fried 1 Family X-linked intellectual disability, Pai type 1 Family X-linked recessive intellectual disability macrocephaly - ciliary dysfunction 1 Family Craniofacial conodysplasia 1 Family X-linked spinocerebellar ataxia type 4 1 Family X-linked intellectual disability, Stocco Dos Santos Family type Autosomal recessive cerebellar ataxia - saccadic intrusion 1 Family Brachydactyly type A7 1 Family Microtia-eye coloboma-imperforation of the nasolacrimal duct 1 Family Neuropathy with hearing impairment 1 Family Charcot-Marie-Tooth disease type 2B2 1 Family Spinocerebellar ataxia type 26 1 Family 995 Autosomal recessive spastic paraplegia type 14 1 Family 105 Autosomal recessive spastic paraplegia type 25 1 Family 103 Autosomal recessive spastic paraplegia type 23 1 Family 104 Autosomal recessive spastic paraplegia type 24 1 Family 999 Autosomal dominant spastic paraplegia type 19 1 Family 997 X-linked spastic paraplegia type 16 1 Family Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March

50 of families 109 Autosomal dominant spastic paraplegia type 29 1 Family Autosomal dominant Charcot-Marie-Tooth disease type 2G 1 Family Autosomal dominant Charcot-Marie-Tooth disease type 2L 1 Family Oculootodental 1 Family Subepithelial mucinous corneal dystrophy 1 Family Epibulbar lipodermoid - preauricular appendage Family polythelia Spondyloepiphyseal dysplasia, Reardon type 1 Family Developmental delay - deafness, Hildebrand type 1 Family Spondyloepimetaphyseal dysplasia, matrilin type 1 Family Multiple epiphyseal dysplasia, Beighton type 1 Family Intellectual disability, Birk-Barel type 1 Family X-linked myopathy with postural muscle atrophy 1 Family Autosomal dominant spastic paraplegia type 38 1 Family Autosomal recessive spastic paraplegia type 32 1 Family Autosomal recessive spastic paraplegia type 35 1 Family Grayson-Wilbrandt corneal dystrophy 1 Family p15.4 microduplication 1 Family Autosomal dominant proximal renal tubular acidosis 1 Family Non-hypoproteinemic hypertrophic gastropathy 1 Family Spastic paraplegia - Paget disease of bone 1 Family Autoimmune lymphoproliferative with Family recurrent viral infections Spinocerebellar ataxia type 32 1 Family White platelet 1 Family Oculocutaneous albinism type 5 1 Family X-linked dyserythropoetic anemia with abnormal Family platelets and neutropenia East Texas bleeding disorder 1 Family X-linked calvarial hyperostosis 1 Family Autosomal dominant myopia-midfacial retrusionsensorineural hearing loss-rhizomelic dysplasia 1 Family Autosomal dominant spastic paraplegia type 73 1 Family X-linked colobomatous microphthalmiamicrocephaly-intellectual disability-short stature 1 Family Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March

51 For any questions or comments, please contact us: Editor-in-chief :Ana Rath Editor of the report:stéphanie Stéphanie Nguengang Wakap Technical support : Samuel Demarest and Valérie Lanneau The correct form when quoting this document is : «Prevalence of rare diseases: Bibliographic data», Orphanet Report Series, Rare s collection, March 2016, 2 : s listed by decreasing prevalence, incidence or number of published cases This Orphanet Report Series is part of the joint action RD-ACTION which has received funding from the European Union s Health Programme ( ). The content of this Orphanet Report Series represents the views of the author only and is his/her sole responsibility; it can not be considered to reflect the views of the European Commission and/or the Consumers, Health, Agriculture and Food Executive Agency or any other body of the European Union. The European Commission and the Agency do not accept any responsibility for use that may be made of the information it contains.