Prevalence and incidence of rare diseases: Bibilographic data

Transcription

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