Neurofibromatosis type 1 (NF1 [MIM 162200]) is a common autosomal dominant disorder that affects 1/3500 individuals and is caused by deletion or point mutations of NF1, a tumour suppressor gene mapping to 17q11.2. Its main features include café au lait spots, axillary and inguinal freckling, iris Lisch nodules, neurofibromas, and an increased risk of benign and malignant tumours, particularly optic glioma, neurofibrosarcoma, malignant peripheral nerve sheath tumours (MPNSTs),¹ and childhood myeloid leukaemia.²

Over 70% of NF1 germline mutations cause truncation or loss of the encoded protein.

Approximately 5–20% of all NF1 patients carry a heterozygous deletion of usually 1.5 Mb involving the NF1 gene and contiguous genes lying in its flanking regions,^3,4 which is caused by unequal homologous recombination of NF1 repeats (REPs).⁵ Known as the “NF1 microdeletion syndrome,” this condition is often characterised by a more severe phenotype than is observed in the general NF1 group. In particular, NF1 microdeleted patients often show variable facial dysmorphisms, mental retardation, developmental delay, and an excessive number of neurofibromas for age.^3,6–12 The severe phenotype of microdeleted patients may be explained by variations in the expression of the genes involved in the rearrangement, which may be caused by different mechanisms, such as gene interruptions, position effects, and decreased gene dosages.

Although NF1 microdeleted patients generally have different characteristics from those of classic NF1 patients, it remains difficult to foresee the presence of the deletion at an individual level on the basis of clinical observations. Various studies have reported the clinical characterisation of NF1 deleted patients and the precise extent of the deletion has been characterised in a subset.^3–5,13,14 However, no study comparing the incidence of specific clinical signs in NF1 deleted and classical NF1 patients has yet been published. …