Noonan syndrome and RASopathies — formative SAQs

SAQ 1 (10)

A newborn boy is noted on the postnatal ward to have a triangular face, hypertelorism, ptosis, low-set posteriorly rotated ears, a short webbed neck, and widely spaced nipples. The karyotype is 46,XY. An echocardiogram shows pulmonary valve stenosis with dysplastic leaflets. [1] [3]

a) Define the RASopathies and explain why Noonan syndrome is the prototypical member. State the most likely genetic basis and the appropriate confirmatory test. (3 marks) [1] [2]

b) Outline the newborn-period surveillance items, including the timing and rationale of the cardiac investigation. (3 marks) [3] [1]

c) State the coagulation abnormality that is common in Noonan syndrome and explain why it matters for this child's future management. (2 marks) [1] [3]

d) The parents ask about the recurrence risk for their next child. Both parents are clinically unaffected. State the recurrence risk and explain the reasoning. (2 marks) [1] [3]

SAQ 2 (10)

An eight-month-old boy with coarse facial features, deep palmar and plantar creases, severe feeding difficulty, and failure to thrive is found to have hypertrophic cardiomyopathy on echocardiography. A multigene RASopathy panel identifies a pathogenic HRAS variant. [5] [3]

a) State the diagnosis and explain why the clinical picture and the gene are consistent. (3 marks) [5]

b) What additional tumour surveillance is required for this child, and what is the estimated lifetime tumour risk? (3 marks) [5] [1]

c) Outline the key differences in developmental prognosis and cardiac profile between this syndrome and classic Noonan syndrome. (2 marks) [1] [3]

d) Explain why a multigene RASopathy panel is preferred over single-gene PTPN11 testing when a RASopathy is clinically suspected. (2 marks) [4] [1]