Neurofibromatosis type 1 and type 2 — formative SAQs

Question 1 (10 marks)

A four-year-old boy is referred because his preschool teacher noticed "lots of brown spots." On examination he has nine cafe-au-lait macules (the largest 8 mm) and freckling in both axillae. His mother has a few cafe-au-lait spots and one small skin lump. (a) State the diagnostic criteria you apply and whether he meets them. (b) Outline the initial assessment and annual surveillance plan. (c) Explain the genetic basis and recurrence risk. [10]

Model answer

(a) The NIH criteria for NF1 require two or more of seven features: six or more cafe-au-lait macules of at least 5 mm before puberty, axillary or inguinal freckling, two or more neurofibromas or one plexiform neurofibroma, optic pathway glioma, two or more Lisch nodules, a distinctive osseous lesion, and an affected first-degree relative. This boy meets two (cafe-au-lait and freckling), so the clinical diagnosis of NF1 is confirmed. [10]

(b) The assessment completes a structured skin, eye, growth and neurological examination, measures blood pressure, plots height and head circumference, screens development and behaviour, and takes a three-generation pedigree while examining both parents. The annual plan reviews growth, blood pressure, skin, spine, puberty and development, and tests visual acuity and colour vision until at least age eight to detect optic pathway glioma. [1]

(c) NF1 is an autosomal-dominant loss-of-function disorder of the NF1 gene on chromosome 17q11.2 encoding neurofibromin, a RAS-GAP. The recurrence risk to each child of an affected parent is 50 per cent, though expressivity varies. Cascade testing of the mother and first-degree relatives is mandatory, and genetic counselling addresses reproductive options. [5]