Marfan syndrome and heritable connective-tissue disorders — formative SAQs

SAQ 1 (10)

A 14-year-old boy presents with tall stature, a pectus carinatum, a positive wrist-and-thumb sign, and an echocardiogram showing aortic-root dilation at the sinuses of Valsalva. Slit-lamp examination shows superotemporal lens subluxation. There is no relevant family history. [2] [1]

a) State the diagnosis and the cardinal features that confirm it under the revised Ghent nosology. Explain why a karyotype is not the confirmatory test. (3 marks) [2]

b) Explain the two-arm pathophysiology (structural and signalling) and name the molecular discovery that reframed the disease. (3 marks) [3] [1]

c) Outline the lifelong management plan, naming the medical therapy and the result of the Pediatric Heart Network atenolol-versus-losartan trial. (3 marks) [4] [1]

d) Both parents are clinically unaffected. State the recurrence risk for the next child and explain the reasoning, including the role of cascade testing. (1 mark) [1] [2]

SAQ 2 (10)

A two-year-old girl is being assessed for a marfanoid habitus. The slit-lamp examination shows that the lens has dislocated downward and inferonasally. She has global developmental delay. [2]

a) State the most likely unifying diagnosis and the single blood test that confirms it. Contrast the direction of lens dislocation in this condition with that in Marfan syndrome. (3 marks) [2]

b) A different marfanoid infant has a bifid uvula, hypertelorism, and arterial tortuosity on magnetic resonance angiography. Name the syndrome, the gene family, and the feature that most clearly distinguishes it from Marfan syndrome. (3 marks) [5]

c) A third child has translucent skin, easy bruising, and a history of bowel rupture. Name the likely gene and explain which investigation must be avoided and why. (2 marks) [5] [1]

d) Explain why every first-degree relative of a confirmed case of Marfan syndrome deserves assessment and targeted genetic testing. (2 marks) [1] [2]