Genodermatoses and neurocutaneous skin findings — branching viva

Opening branch — the diagnosis

Candidate brief. Take the diagnosis and diagnostic criteria first. [1]

• What is the most likely diagnosis, and which National Institutes of Health consensus criteria does this child meet? Name the seven features. [1]
• How does the caf\u00e9-au-lait macule threshold differ before and after puberty (six or more, at least five millimetres prepubertal and fifteen postpubertal)? [1] [2]

Second branch — the pathophysiology and the shared signalling story

Examiner pivot. Now the biology. [2]

• What gene is affected in neurofibromatosis type 1 and what protein does it encode? Loss of NF1 on chromosome 17, loss of neurofibromin, releasing the RAS-MAPK pathway. [2]
• How does tuberous sclerosis share this signalling family? Loss of TSC1 or TSC2 removes the hamartin-tuberin brake on mTORC1, driving the dysplastic hamartomatous growth. [3]

Third branch — surveillance and the dangerous complications

Examiner pivot. What does this child need, and what must you not miss? [2]

• Outline the annual medical-home surveillance for NF1: vision (optic pathway glioma), blood pressure (renal artery stenosis, phaeochromocytoma), growth, skin, and learning and behaviour. [2]
• What is the malignant peripheral nerve sheath tumour red flag in a changing plexiform lesion, and what would you do? [2]

Fourth branch — the contrast with Sturge-Weber

Examiner pivot. Contrast this inherited phakomatosis with the sporadic mosaic one. [5]

• What mutation causes Sturge-Weber, and why is it sporadic and confined to one territory? A somatic mosaic GNAQ mutation arising postzygotically. [5]
• Why does a port-wine stain on the forehead or upper eyelid mandate a contrast brain magnetic resonance image and ophthalmology? The risk of a leptomeningeal angioma and glaucoma. [6] [5]

Closing — the tuberous sclerosis parallel

• For tuberous sclerosis, what is first-line for infantile spasms and what treats the growing subependymal giant cell astrocytoma? Vigabatrin first-line, and the mTOR inhibitor everolimus. [4] [3]