Neurofibromatosis type 1 and type 2 — branching viva

Branching viva on neurofibromatosis: applying the NIH diagnostic criteria for NF1, explaining the neurofibromin/RAS mechanism, building surveillance around optic glioma and plexiform neurofibroma, and separating NF2 as a chromosome-22 merlin disorder of bilateral vestibular schwannomas.

branching clinical structured oral2 min readVerification in progress

Prompt

Outpatient clinic: a three-year-old girl with eight cafe-au-lait macules and axillary freckling, a normal developmental screen, and a father with a few cafe-au-lait spots and a single cutaneous lump. The examiner asks: what diagnostic criteria do you apply and does she meet them, what is the molecular basis, how would you explain the diagnosis and recurrence risk to the family, and what is the surveillance plan — then branches to a painful, rapidly enlarging lump on her thigh and asks how you would assess and investigate it, and finally to a 17-year-old with unilateral hearing loss and a family history of vestibular schwannoma and asks how this is a different disease.

Opening framework

My framework has four layers. First, the diagnosis \u2014 NF1 is a clinical diagnosis built from the NIH criteria, and this child with eight cafe-au-lait macules and axillary freckling already meets two of the seven, so she has NF1. Second, the mechanism \u2014 a loss-of-function variant in NF1 on chromosome 17 that abolishes neurofibromin, the RAS-GAP that switches off active RAS. Third, the surveillance \u2014 annual review of growth, blood pressure, vision, skin and development. Fourth, the family \u2014 cascade testing and counselling on the 50 per cent autosomal-dominant recurrence risk. [1]

Paediatrics Fellowship Pro

You have read the opening of this viva. The complete unit — every section and its primary-source references — is part of the Paediatrics Fellowship fellowship atlas.

References5Show ledger

[1]Gutmann DH, Ferner RE, Listernick RH, et al. Neurofibromatosis type 1. Nat Rev Dis Primers, 2017.PMID 28230061
[2]Asthagiri AR, Parry DM, Butman JA, et al. Neurofibromatosis type 2. Lancet, 2009.PMID 19476995
[5]Legius E, Messiaen L, Wolkenstein P, et al. Revised diagnostic criteria for neurofibromatosis type 1 and Legius syndrome: an international consensus recommendation. Genet Med, 2021.PMID 34012067
[8]Gross AM, Wolters PL, Dombi E, et al. Selumetinib in Children with Inoperable Plexiform Neurofibromas. N Engl J Med, 2020.PMID 32187457
[10]Williams VC, Lucas J, Babcock MA, et al. Neurofibromatosis type 1 revisited. Pediatrics, 2009.PMID 19117870