Williams syndrome — formative SAQs

SAQ 1 (10 marks)

An eight-month-old infant is referred for failure to thrive, persistent irritability, and chronic constipation. On examination she has a distinctive facies with periorbital fullness and a stellate iris, a loud harsh ejection systolic murmur radiating to the neck, and a four-limb blood pressure that is elevated. Serum calcium is markedly raised. [1] [5]

a) Give the unifying molecular diagnosis and name the chromosomal abnormality, the key gene responsible for the cardiovascular findings, and the first-line confirmatory laboratory test. (3 marks) [2] [5]

b) Explain why haploinsufficiency of this gene produces stenotic arteries rather than aneurysms, and name the two coronary and outflow consequences that most threaten this child's life. (3 marks) [3] [5]

c) Outline the immediate and ongoing management of her infantile hypercalcaemia, naming four interventions. (2 marks) [6] [1]

d) State the inheritance pattern and the recurrence risk in a future pregnancy if a parent is found to carry the deletion, and outline the cardiac surveillance obligation. (2 marks) [1] [3]

SAQ 2 (10 marks)

A four-year-old boy with a confirmed Williams syndrome diagnosis is scheduled for dental extraction under general anaesthesia. His parents have been told he is "very clever" because he speaks fluently and greets everyone warmly. The dentist asks whether the anaesthetic can be done as a day case in a community clinic. [2] [7]

a) Explain to the dentist why this child should not have anaesthesia in a community day-case setting, naming the specific cardiovascular and coronary risks and the mandatory pre-operative assessment. (3 marks) [3] [7]

b) Address the parents' assumption that their son is "very clever": explain the Williams syndrome cognitive profile, naming the relative strength and the relative weakness, and the implication for his education. (3 marks) [1] [2]

c) Outline the multidisciplinary health-supervision plan for this child beyond the dental procedure, naming four surveillance domains anchored to the AAP 2020 clinical report. (2 marks) [1]

d) Describe how you would distinguish Williams syndrome from familial isolated supravalvular aortic stenosis, and why that distinction changes the counselling. (2 marks) [5] [2]

Marking guide

SAQ 1. The unifying diagnosis is Williams (Williams-Beuren) syndrome, caused by a microdeletion at chromosome 7q11.23 (approximately 1.5 to 1.8 Mb). The key gene driving the cardiovascular findings is ELN (elastin), and the first-line confirmatory test is a chromosomal microarray (FISH is the historical confirmatory test). ELN haploinsufficiency reduces elastic lamellae in the arterial media, provoking excessive smooth-muscle proliferation and a thickened, disordered media, which narrows vessels — hence stenosis, not the aneurysm seen in Marfan-type matrix disorders. The two life-threatening consequences are coronary artery stenosis (causing ischaemia and sudden death, especially under anaesthesia and with exertion) and progressive supravalvular aortic stenosis (left-ventricular outflow obstruction and heart failure). Hypercalcaemia management: intravenous hydration if dehydrated, withdraw calcium and vitamin D supplementation, a low-calcium formula, and serial calcium monitoring (bisphosphonates only in severe crisis under metabolic guidance). Inheritance is autosomal dominant: if a parent carries the deletion the recurrence risk is 50 percent per pregnancy (most cases are de novo). Cardiac surveillance is lifelong: baseline and serial echocardiography, four-limb blood pressure at every visit, coronary assessment, and cardiology-led follow-up. [1] [2] [6]

SAQ 2. Anaesthesia in a community day-case is contraindicated: Williams syndrome carries a recognised risk of sudden cardiac death under anaesthesia driven by coronary artery stenosis and an unstable outflow tract, plus labile blood pressure and difficult airway. The procedure requires a centre with dedicated paediatric cardiac anaesthesia, a pre-operative echocardiogram and coronary assessment (CT or MR angiography where indicated), invasive blood-pressure monitoring, and avoidance of sudden haemodynamic shifts. The cognitive profile is a relative strength in verbal ability, auditory-rote memory, face recognition, and musical affinity set against a marked weakness in visuospatial construction, numeracy, and daily-living skills — the fluent, sociable speech ("cocktail-party" loquacity) masks a real mild to moderate intellectual disability, so the education plan must support the spatial and daily-living deficits explicitly rather than relying on the verbal impression. Health supervision (AAP 2020): cardiology-led serial echocardiography and blood-pressure surveillance, calcium monitoring, thyroid screening, renal ultrasound, audiology and vision, dental, and developmental and educational support. Williams syndrome is distinguished from familial isolated supravalvular aortic stenosis by the latter's ELN point mutation (or ELN-region-only deletion) with normal facies and normal cognition — the arteriopathy is shared but the developmental prognosis and the autosomal dominant counselling differ, so a dysmorphic, developmentally delayed child should not be conflated with an ELN-mutation family. [3] [7] [2]