Paediatric Syndromes

Di George Syndrome

Answer explanation

22q11.2 deletion (95%), otherwise 10p13 deletion 1 in 4000 AD inheritance (majority de novo) Complete Di George = thymic aplasia (1%), remainder parital Di George Results from dysmorphogenesis of 3rd/4th pharyngeal pouches --> hypoplasia of thymus/parathyroid glands Features (CATCH-22): - Cardiac (esp TOF + truncus arteriosus, DORV, CoA) - Abnromal facies (short philtrum, hypertelorism, antimongoloid eye slant, mandibular hypoplasia, low-set, notched ears) - Thymic hypoplasia (60 - 80% with low T cells) - Cleft palate - Hypocalcaemia/hypoparathyroidism Other feats incl. oesophageal atresia, bifid uvula, Schizophrenia/ADHD, enamel hypoplasia, dysplastic kidneys 1/3 have CHARGE association - Coloboma, Heart defect, Atresia (Choanal), Retardation of growth, Genital hypoplasia, Ear abnormalities incl. deafness

Williams Syndrome

Answer explanation

Multiple gene deletions of long arm of Ch7 1 in 7,500 Feats include: - Elfin like facial features - Cocktail party demeanor - Widely spaced teeth - Flat nasal bridge - Long philtrum - Developmental delay with STRONG language skills Cardiac probs: - Supravalvular AS - Peripheral PS Dx by FISH or microarray

Noonan Syndrome

Answer explanation

AD inheritance Mutation in RAS/Mitogen activated protein kinase signalling pathways on different genes (70%) - not same gene, therefore CLINICAL DIAGNOSIS 1 in 1,000 (similar to Tri 21) AKA Turner's for boys Feats: - Physical (MR SHEEN) MOUTH: deeply grooved philtrum, micrognathia, high arched palate ROEDEMA: oedema of hands/feet (early) STATURE: short, pectus excavatum, winging of scapula HEAD: excess skin on nape, low post hairline, high ant hairline, macrocephaly, traingular face, short webbed neck EYES: hypertelorism, ptosis, epicanthal folds, refractory errors EARS: low-set, posteriorly rotated, thick helix, COM NOSE: small + upturned - Cardiac: PS (50%), ASD/VSD, Cardiomyopathy - Genital: undescended testes - Developmental: delayed - Haematological: blood clotting disorders

Alagille Syndrome

Answer explanation

AD 1 in 100,000 Microdeletion of 20p12 corresponding to JAG1 gene Feats: - Cardiac: Peripheral PS, PS, TOF - Liver: Bile duct paucity (absence/marked reduction in number of interlobular bile ducts) - Facies: Broad forehead, deep-set widely spaced eyes, long straight nose, short pointed chin - Vertebral: Butterfly vertebrae, fused vertebrae, spina bifida occulta

Cornelia De Lange Syndrome

Answer explanation

Majority are spontaneous mutations - 50% d/t mutation of NIPBL gene on Ch5 1 in 30,000 CLINICAL DIAGNOSIS, but can test for above mutation Feats (FOB): FACE: microcephaly, synophrys, long eye lashes, long philtrum, low-set ears, short upturned nose, thin downturned lips OTHER: developmental delay (severe speech delay + mild-moderate MR), seizures (23%), congenital heart disease (VSD/ASD in 25%), GORD (90%), behavioural problems BODY: excessive body hair, abN limbs (micromelia, oligodactyly, clinodactyly, syndactyly)

Trisomy 13 (Patau Syndrome)

Answer explanation

Trisomy 13 1 in 10,000 Increased risk with increased maternal age Feats: CNS: MR, microcephaly, micropthalmia MSK/SKIN: polydactyly, low-set ears, prominent heel, rocker bottom feet, omphalocoele, overlapping of fingers over thumb, cutis aplasia, cleft palate GENITALS: kidney defects, abN genitals CLUE: single umbilical artery 80% die in first year of life Unless parent is translocation carrier, risk of recurrence <1%

Trisomy 18 (Edwards Syndrome)

Answer explanation

Trisomy 18 1 in 6,000 80% are female Most die before birth Increased risk with increased maternal age Feats: CARDIAC: VSD/ASD, PDA, CoA, Bicuspid aortic/pulm valve RENAL: malformations GIT: Omphalocoele, oesophageal atresia MSK: Arthrogryposis DEVELOPMENT: delayed PHYSICAL FEATS: microcephaly, prominent occiput, low-set ears, micrognathia, cleft lip/palate, upturned nose, narrow palpabrel fissures, hypertelorism, short sternum, ptosis, clenched hands, absent radius, webbed 2nd/3rd toes, rocker-bottom feet 50% die in first week of life Only 8% survive beyond 1 yo

Trisomy 21 (Down Syndrome)

Answer explanation

1 in 733 (doesn't account for spontaneous abortion) Tri 21 Hall's criteria for Dx - Hypotonia - Poor moro reflex - Flat face - Upward slanted palpebral fissures - Small dysplastic features - Joint hyperflexibility - Short neck, loose skin folds - Short 5th digit with clinodactyly - Single transverse palmar crease - Pelvic dysplasia Other feats: Craniofacial - brachycephaly, flat occiput, prominent epicanthal folds, speckled irises (Brushfield spots), 3 fontanelles with delayed closure, midface hypoplasia, mild microcephaly, short hard palate, small nose with flat nasal bridge, protruding tongue MSK - short metacarpals/phalanges, wide-spaced 1st/2nd toes, short sternum GIT - duodenal atresia, TOF, annular pancreas, Hirschsprung's, imperforate anus Skin - cutis marmorta Susceptibilities: - congenital heart disease, esp AVSD (less commonly ASD/VSD) - hypothyroidism - megaloblastic luekaemia + lymphoproliferative disorders (solid tumoure rare in Tri21) - immune dysfunction - diabetes - hearing and vision problems - Alzheimer's disease-like dementia (4th decade of life) - developmental delay Dx: by clinical feats and karyotype, but also do chromosome analysis to rule out translocation cuase, as recurrence risk is 100%

Turner Syndrome

Answer explanation

1 in 2,000 45, XO (ie absence of second X chromosome in girls) Clincal feats: From birth - oedema of dorsum of hands/feet - loose skin folds at nape of neck - low birth weight - low body length Childhood - webbing of neck - low posterior hairline - small mandible - prominent ears - epicanthal folds - high-arched palate - broad chest with wide spaced nipples - cubitus valgus - hyperconvex finger nails - short stature - sexual maturation failure (adrenarche normal, but delayed pubarche, and have premature menopause (infertile by 2 yo) NORMAL INTELLIGENCE Other problems: - Congenital heart disease, esp bicuspid aortic valve, aortic dilatation, partial anomalous pulmonary venous drainage, CoA, AS, MV prolapse - Premature coronary artery disease - Renal malformations (risk of HTN and UTI's) - 30 - 50% have thyroid autoantibodies, therefore potential for autoimmune thyroid disease - increased risk of coeliac disease Mx - growth hormone in early childhood for short stature and oestrogen replacement in adolescence

Beckwith-Wiedemann Syndrome

Answer explanation

Overgrowth disorder 1 in 13,700 (increased in IVF 3-4 fold) 85% sporadic, 15% familial d/t dysregulation of imprinted expression in Ch11p15.5 region (paternal gene imprinted). Affects critical genes in domain 1 (IGF-2 (overexpression of foetal growth factors) and H19 (tumour suppressor gene)) 5 common feats: Macroglossia Macrosomia Midline abdominal wall defects Ear creases/pits Neonatal hypoglycaemia Other possible feats incl. port wine stain, prominent occiput, midface hypoplasia, hemihypertrophy, cardiomyopathy, nephromegaly, hearing loss INCREASED RISK of childhood cancer (600-fold) esp embryonal tumours (Wilm's + hepatoblastoma), and less likely andrenal coritcal carcinoma, neuroblastoma and rhabdomyosarcoma Screened for Ca with 3 monthly abdo U/S until 8 yo and 6 weekly AFP for hepatoblastoma