Dental Manifestations of Genetic Syndromes and Treatment Challenges. June Nunn Trinity College Dublin

Transcription

1 Dental Manifestations of Genetic Syndromes and Treatment Challenges June Nunn Trinity College Dublin

2 Definitions Malformations: morphological defect of an organ resulting from abnormal development eg cleft lip Deformation: Mechanical compression eg clubfoot Disruption: breakdown of developmental process eg amniotic band amputation Syndrome: A pattern of multiple anomalies, which are pathologically related and not a single sequence or field defect eg Trisomy 21 Sequence: pattern of multiple anomalies derived form known anomaly or mechanical factors eg Pierre Robin

3 Syndrome Aetiology Chromosomal disorders eg Cri du Chat Single gene disorders eg Crouzon s Multifactorial inheritance eg Cleft lip/palate

4 Chromosomal Abnormalities Deletions (Williams), duplications (5p-), inversions, translocations (Down syndrome) Microdeletions (Prader Willi) Mosaicism (Osteogenesis Imperfecta, Aperts)

5 Genetic Heterogeneity Genetic heterogeneity clinical similarity produced by different genes- Tuberous sclerosis 9q33-q34 or sited at 16p13.3 Uniparental disony 2 copies of chromosome come from one parent, none from the other seen in Cystic Fibrosis, Prader Willi syndrome Genomic imprinting modification to genetic material depending on whether paternally or maternally derived eg chromosome 15 paternal deletion = Prader Willi syndrome, maternal deletion = Angleman s syndrome Imprinting and uniparental disony Beckwith Wiedemann syndrome

6 Single Gene Disorders Autosomal dominant eg Russell Silver syndrome, Epidermolysis Bullosa (and AR) Autosomal recessive Rothmund- Thompson syndrome, Bartter syndrome X-linked AR Hypohidrotic Ectodermal Dysplasia X-linked AD - Vitamin D Resistant Rickets, Rett s syndrome, orofacialdigital syndrome Type 1

7 Sporadicity Can be AD or AR, also occurs with variant additive patterns (minor abnormalities, normal for that family) plus major abnormality, eg Noonan s syndrome. May be a link with Klippel Feil and Moebius -? via intrauterine disruption of Vertebral or Subclavian artery

8 Anticipation Progressive earlier appearance and increasing severity of a disorder caused by expansion of genes as a result of repeated base sequences leading to gene instability. If this exceeds a threshold, mutation occurs, during female meiosis in Fragile X syndrome, Myotonic Dystrophy

9 Multifactorial inheritance Combination of genetic and environmental factors eg Spina Bifida, Cleft Palate Risk is greatest in 1 st degree relatives Risk increases with each family member affected (4% for sibling, 16% if one parent affected) Risk increases if malformation severe If sex differences in frequency, risk increases when trait occurs in less frequently affected sex Risk increases if parents are consanguinous

10 Genetic Syndromes Dental manifestations and challenges

11 Cri du Chat syndrome One of commonest deletions short arm of Chromosome 5; cat-like cry (laryngeal deformity), Microcephaly, learning disability, hyperteloric Delayed eruption, malocclusion, micrognathia

12 Crouzons and Apert s syndrome Autosomal inheritance, mutation in fibroblast growth factor gene (chromosome 10) Craniosynostosis (Aperts + syndactyly) Mid-face hypoplasia, high vaulted palate/cleft, conductive hearing loss Hydrocephalus/seizures

13 William s syndrome Due to deletion of elastin gene, chromosome 7 Supravalvular aortic stenosis and other CHDs - 3% incidence of sudden death Cerebral and renal artery stenosis Hypotonia hypertonia Attention deficit disorder Hyperaceusis Enamel hypoplasia

14 Prader Willi syndrome Paternal part-deletion of long arm chromosome 15 Pulmonary hypertension secondary to hypoventilation Short stature, obese, low IQ, behavioural problems with food, NIDDM Relatively insensitive to pain Abnormal temperature control

15 Down syndrome CHD/pulmonary hypertension Thyroid problems Coeliac disease Epilepsy Early disintegrative disorder (Alzheimers) Pharyngeal airway hypotonia Atlantooccipital instability lax cervical ligaments Leukemoid reaction to infections Cataracts

16 Down syndrome dental considerations Learning disability Macroglossia Deep vaulted palate Enamel hypoplasia Short roots Delayed eruption/shedding of primary teeth

17 Fragile X syndrome X-linked fragility of X chromosome caused by folate deficiency/antagonists Common in males in long-stay residential care with LD of unknown origin Fragile XE similar, less severe learning disability Low set ears, prognathism, crowding,? Submucous cleft Mitral valve prolapse

18 Beckwith syndrome Sporadic normal chromosomes; Defects in 11p15.5 (paternal duplicate, maternal translocations); or AD.Subsets - underexpression of P57 gene and over- expression of insulin-like growth factor-2 gene Macrosomia, visceromegaly (risk of abdominal tumours),omphalocele Macroglossia, malocclusion, micrognathia Cardiac defects Hypoglycaemia in the infant

19 Myotonic dystrophy AD multi-system disease gene defect of a kinase that limits the intracellular sodium current Successive generations more severely affected anticipation defect 90% have cardiac conduction defects Facial weakness, facial diplegia, tent-shaped mouth, dysphagia (aspirate) Abnormal insulin response to glucose; colloid goitre

20 Ectodermal Dysplasias Group of conditions Xlinked AR Affects eyes, skin, hair, nails, hearing and teeth Hypodontia, microdontia, enamel hypoplasia Abnormal temperature regulation- perioperative hyperpyrexia (sedation + GA)

21 Ectodermal Dysplasias (2) Principles of dental care: Prevent dental disease Restore function Restore aesthetics Retain OVD Boost self-esteem

22 Epidermolysis Bullosa 20 different types: Simplex bullae heal with no scarring Junctional and dystrophic bullae at or below basement membrane and heal with scarring Neoplasia of skin lesions Scarring limits mouth opening, produces pseudosyndactyly Mitral valve prolapse

23 Osteogenesis Imperfecta Gene mutation for type I collagen Types I, III and IV are AD, Type II usually lethal in Utero (AD or AR) Cardiac defects, kyphoscoliosis, platelet dysfunction (Type I) Intra-operative hypermetabolic state not malignant hyperpyrexia Frequent fractures bisphosphonate therapy increases bone quality

24 Osteogenesis Imperfecta Type 1, commonly blue sclera, dentinogenesis imperfecta, hearing loss

25 Vitamin D Resistant Rickets X-linked AD, PEX gene involved in peptide synthesis Defect due to hypophosphataemia Short stature, craniosynostoses, sensorineural deafness Abnormal dentine formation leading to dental abscesses

26 Rett syndrome X-linked, AD, exclusive to females Progressive encephalopathy, regressive from months Characteristic hand writhing, choreoathetosis, dementia/autism like symptoms, seizures, decreased sensitivity to pain Music may reduce behavioural disturbances

27 Orofacial Digital Syndrome X-linked, AD, predominantly female Lethal in males 9 different types Clefts, clefts of alveolar ridges + banding Papilliform appearance of tongue/ multiple oral fraenae Polycystic kidneys with age renal failure

28 Jeune syndrome Asphyxiating thoracic dystrophy Severe respiratory insufficiency Renal failure Hepatic insufficiency/pancreatic fibrosis Hypodontia

29 Noonan s syndrome Sporadic, AD, variant additive pattern - familial occurrence Similarities with Turner (but males and females affected), Klippel Feil and Moebius syndrome? Due to disruption in utero of subclavian or vertebral arteries Web neck, learning disabilities, coagulation defects (Factor XI, VWD)

30 Noonan s syndrome Pulmonary hypertension Sensioneural hearing loss Depressed nasal bridge, flattened mid-face Malocclusion, high arched palate, micrognathia Malocclusions Delayed eruption?

31 General management principles Communication aids Consent and autonomy

32 General management principles Access to care positioning/ comfort Physical interventions ( Restraint )

33 Aggressive Prevention- - diet Work with dieticians nutritional supplements, PEG feeding, sweetened medicines, saliva substitutes

34 Aggressive Prevention - fluorides High dose fluorides for at-risk patients Continuously reassess and monitor risk Check compliance

35 Aggressive Prevention Oral hygiene as part of Care Plan See parents/carers carrying out oral hygiene routines Advise on appropriate aids

36 Dental treatment Minimally invasive Chemicomechanical/ART Ozone therapy Radical treatment planning if GA

37 Maintenance Regular follow up faciltiators Follow-through from childhood into adulthood??? Bridging the Gaps: Health Care for Adolescents June 2003 Royal College of Paediatrics and Child Health

38 Acknowledgments All the patients who made me humble for how well they coped with what life s challenges threw at them Annmarie Boon for scanning all their pictures, late into each evening