The clinical features and genetic linkage analysis of two pedigrees with familial spinal neurofibromatosis (NF) are described from the Divisions of Neurology and Medical Genetics, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CA; the Neurofibromatosis Institute, Pasadena, CA; and Department of Medical Informatics, University of Utah, Salt Lake City, UT. On clinical grounds, it was difficult to assign the two families to NF1 or NF2 based on the criteria established by the National Institutes of Health. Cutaneous tumors, Lisch nodules or acoustic tumors were absent. Cafe-au-lait spots were present in 1 family and absent in the other. The inheritance pattern was autosomal dominant in both pedigrees. Genetic linkage analysis was performed with markers linked to the NF1 gene on chromosome 17 and markers linked to the NF2 gene on chromosome 22. The location for the mutation in the first family was in the NF1 gene, whereas that in the second family was excluded from the NF1 locus, although the phenotype was similar to that of family 1. [1]

COMMENT. Studies of families in which all affected individuals express the same subset of the NF phenotype allow a correlation between the mutation and its clinical characteristics. Symptomatic spinal neurofibromas occur in less than 5% of patients with NF1, but are commonly found in NF2. This may be the first report of familial spinal neurofibromatosis in families with NF1. One individual in each pedigree developed a neurofibrosarcoma and died of its complications. This is a rare complication in NF1, explained by the authors as a familial predisposition related to the mutations.