Marfan syndrome and heritable connective-tissue disorders — branching viva

Opening question

A 14-year-old with tall stature, a positive wrist-and-thumb sign, superotemporal lens subluxation and aortic-root dilation at the sinuses of Valsalva, with no family history. What is the unifying diagnosis, how is it confirmed under the revised Ghent nosology, and why is a karyotype not the confirmatory test? [2] [1]

Branch 1 — the mechanism and the medical therapy

Take the same boy. Explain the two-arm pathophysiology of fibrillin loss, and explain why losartan was a rational therapy. What did the Pediatric Heart Network atenolol-versus-losartan trial show, and how does it change what you prescribe? [3] [1]

Branch 2 — pregnancy and the root

At 17 the same patient wants to become a parent; her most recent aortic root is 4.4 cm. What is the pre-conception plan, and why is a root greater than 4.0 cm a red flag? [1]

Branch 3 — the dangerous relatives

A different child has a bifid uvula, hypertelorism and arterial tortuosity. Name the syndrome, the gene family, and the single feature that most clearly distinguishes it from Marfan syndrome. Then: a marfanoid toddler with translucent skin and easy bruising presents with arterial rupture — which investigation must you avoid and why? [4] [5]

Closing — the lens that fell down

A marfanoid child whose lens has dislocated downward and inferonasally, with developmental delay. In one sentence, what is the diagnosis, what is the confirmatory test, and why does labelling this as Marfan change the outcome? [5] [2]