Williams syndrome

Williams syndrome results from a contiguous gene deletion at 7q11.23, most commonly a de novo microdeletion encompassing ~26-28 genes, including ELN (elastin). Haploinsufficiency of elastin leads to elastin arteriopathy, manifesting as supravalvular aortic stenosis (most common cardiac lesion), pulmonary artery stenosis, and other vascular narrowing (can predispose to hypertension due to vascular stiffness).

Clinical features include: - Distinctive facial features: broad forehead, periorbital fullness, medial eyebrow flare, short nose with bulbous nasal tip, long philtrum, wide mouth with full lips, small chin - often described as 'elfin facies' - Cardiovascular: supravalvular aortic stenosis, peripheral pulmonary stenosis, hypertension - Endocrine: hypercalcemia in infancy (mechanism not fully understood, possibly related to abnormal vitamin D metabolism or calcium-sensing receptor dysfunction) - Neurodevelopmental: mild to moderate intellectual disability with relative strength in language/verbal skills but significant deficits in visuospatial construction - Behavioral phenotype: hypersociable, overly friendly, empathetic, anxious, particular affinity for music - Growth: failure to thrive in infancy, short stature - Other: distinctive stellate iris pattern, dental abnormalities, joint laxity that can progress to joint limitation, connective tissue abnormalities

Diagnosis is confirmed via FISH or chromosomal microarray demonstrating deletion at 7q11.23.

Management is multidisciplinary: cardiology follow-up (echocardiograms to monitor stenosis progression), monitoring calcium levels, developmental/educational support, and monitoring for hypertension.

High-yield board associations: 'Elfin facies' + supravalvular aortic stenosis + hypercalcemia + friendly/cocktail party personality = Williams syndrome. Contrast with Down syndrome (different facial features, different cardiac lesions like AV septal defects) and DiGeorge syndrome (22q11 deletion, different phenotype).