111 Williams Syndrome
Williams Syndrome 931
WMS, Williams-Beuren syndrome, elfin facies syndrome
Typical facies with dependent cheeks and full lips, mental retardation, growth deficiency, cardiovascular anomalies, infantile hypercalcemia
Frequency: 1 in 10,000–20,000 births.
Genetics
Autosomal dominant (OMIM 194050), with few in- stances of parent-to-child transmission because affected individuals usually do not reproduce; most reported cases sporadic; contiguous gene syndrome resulting from a 1.55–1.84 Mb deletion that includes the elastin gene (ELN, responsible for the vascular and connective tissue changes) at 7q11.23 in over 95% of cases; other disrupted genes may include LIM-Kinase 1 (LIMK1, possibly responsible for im- paired visuo-spatial perception), replication factor C (RFC2, possibly responsible for deficient growth), frizzled FZD3 gene, syntaxin STX1A gene, and WSCR-1 and -2.
Clinical Features
• Intrauterine growth retardation, short stature
• Characteristic ‘elfin’ facial appearance, with flat midface, depressed nasal bridge, anteverted nares, long philtrum, wide mouth, prominent lips, and full cheeks; broad forehead, hypotelorism (50%), short palpebral fissures (50%), epicanthal folds (50%), strabismus (50%), esotropia (40%), hyper- metropia (75%), stellate iris pattern (50–75%), prominent ears, dental malformations
• Pectus excavatum
• Clinodactyly of 5th fingers, hallux valgus, hy- poplastic, deep-set nails (65%)
• Cardiovascular defects (75%), notably supra- valvular aortic stenosis and pulmonary artery stenosis, other defects include aortic hypoplasia, aortic coarctation, mitral valve prolapse, bicuspid aortic valve, left coronary artery stenosis, renal ar- tery stenosis, multiple peripheral pulmonary arte- rial stenoses, other peripheral artery stenoses, atrial or ventricular septal defects, anomalous pul- monary venous return, AV fistula, atretic portal vein, systemic hypertension
• Chronic constipation, diverticulosis, inguinal or umbilical hernias, rectal prolapse
• Renal anomalies (unilateral renal agenesis, kidney duplication, cystic dysplasia), bladder diverticula (10%)
• Progressive joint limitation (elbows, hips)
• Mental retardation (95%) mild neurological dys- function (50%), impaired visuospatial construc- tive cognition, attention deficits, extroverted per- sonality (65%), hyperacusis (95%), gait abnor- malities
• Hoarse voice
• Infantile hypercalcemia, nephrocalcinosis Differential Diagnosis
• Isolated supravalvular aortic stenosis
• Idiopathic hypercalcemia
Radiographic Features Skull
• Maxillary hypoplasia, wide maxillary arch
• Prognathism or mild micrognathia
• Widened mandibular angle
• Hypodontia, microdontia, small roots, anterior crossbite, increased interdental spacing, delayed mineralization of teeth, osteosclerotic changes in the lamina dura
• Craniosynostosis, mild microcephaly (35%) Generalized Skeletal Abnormalities
• Transverse metaphyseal bands of increased bone density, sclerosis in severe cases (reversible)
• Ectopic calcification
• Joint limitations Hands and Feet
• Clinodactyly of 5th finger (40%), camptodactyly
• Hallux valgus (75%)
• Talipes equinovarus Extremities
• Radioulnar synostosis (8–25%) Spine
• Kyphoscoliosis (20%)
• Lumbar hyperlordosis Chest
• Pectus excavatum
W
Williams Syndrome 932
Fig. 111.1. a Patient 1, age 3 months; b patient 2, 14 years;
cpatient 3, adult. Broad forehead, depressed nasal bridge, long philtrum, anteverted nostrils, wide mouth with prominent lips, and full cheeks
a
c
b
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Williams Syndrome 933
