Editor—Neurofibromatosis type 1 (NF1) is a common human disorder (1/3500 live births) with neuroectodermal involvement resulting in dermatological manifestations of café au lait spots, cutaneous/subcutaneous neurofibromas, and freckling of major folds.1 Hamartomas of the irides (Lisch nodules), well observed on slit lamp examination, are helpful phenotypic markers. Owing to diagnostic uncertainties, especially in young patients, an international scoring system has been discussed and agreed upon.2 Half of the cases result from fresh mutations, others show an autosomal dominant mode of inheritance. The gene mutated in NF1 maps to 17q11.2, is composed of 57 plus at least three alternatively spliced exons,3 and is of ubiquitous expression. The encoded product, referred to as neurofibromin, is a member of the so called GTPase activating proteins (GAPs), and is an upstream downregulator of the p21Ras/Raf/MAPkinase signalling pathway.4 Though genetic homogeneity is a hallmark of this condition, phenotypic heterogeneity has been exemplified by an extreme spectrum of diversity ranging from malformation or malignant variants to virtually benign dermatological changes.1

In particular, and among the many causes for gastrointestinal involvement in NF1 patients, the association with intrinsic intestinal dysmotility (IID), resulting from intestinal neuronal dysplasia type B (IND B)5 6 or aganglionic megacolon (Hirschsprung's disease, HSCR)7 has been documented and is now well established.

We report here a family showing aggregation of NF1 and IID in two sibs, in one of whom congenital megacolon necessitated a Duhamel abdominoperineal pull through with tired suction biopsies of the colon and analysis of the whole excised specimen indicating IND B. This kindred provided a unique opportunity to unravel the genetic bases for the association between two such disorders of neural crest cell development.

The proband was seen at the age of 27 months for investigation of a multiple congenital anomaly/mental retardation (MCA/MR) complex. This young female …