The Genetic Aspects of Neurofibromatosisa

Abstract

Although the genetic pattern in NF has been definitely established as autosomal dominant, more precise data regarding penetrance, natural history, prevalence, and heterogeneity are needed for the counseling of families. NF is the prototypic disorder for the study of the biologic mechanisms of variable expressivity. The widely cited prevalence figure of Crowe is probably too high; thus the mutation ratio estimation in NF is among the highest in man but close to other common Mendelian disorders. With the existing data on frequency of Lisch nodules and with future prospective date on café-au-lait spot development, an age-of-onset penetrance curve for NF could be constructed for genetic counseling purposes. The segmental form of NF is of interest as cases of this presentation may be helpful in studying the hypothesis of human somatic mutation when DNA analysis is available. Guidelines for routine evaluation and ongoing health supervision of individuals with neurofibromatosis need to be developed; multidisciplinary NF clinics and collaborative study groups are appropriate settings for this undertaking. Neurofibromatosis is an important disorder for the study of the psychodynamic processes that families experience in dealing with uncertainty.

Neurofibromatosis-Noonan syndrome: Molecular evidence of the concurrence of both disorders in a patient

“…Neurofibromatosis type 1 (NF1) (OMIM 162200) is an autosomal dominant disorder with café-au-lait spots, neurofibromas, Lisch nodules, axillary and inguinal freckling, optic nerve glioma, and skeletal abnormalities [Carey et al, 1986]. The responsible gene, NF1, encodes a GTPase activating protein (neurofibromin) that acts as a negative regulator of RAS signaling [Xu et al, 1990].…”

NF1 microdeletions in neurofibromatosis type 1: from genotype to phenotype

“…Neurofibromatosis type 1 (NF1; MIM# 162200) is an autosomal disorder with an estimated incidence of 1 in 3500 live births (Carey et al, 1986). NF1 is due to autosomal dominant loss-of-function mutations of the NF1 gene (neurofibromin 1; NM_000267), a tumour suppressor gene located at 17q11.2 and containing 60 translated exons distributed over ~300 kb.…”

Cancer of the Peripheral Nerve in Neurofibromatosis Type 1

“…The RASopathy neurofibromatosis 1 (NF1) is an autosomal dominant hereditary cancer syndrome that affects~1 in 3000 individuals [1]. The diagnosis of NF1 is based on National Institutes of Health clinical consensus criteria [2,3], with the main clinical features including multiple café-au-lait macules, axillary freckling, Lisch nodules, optic pathway gliomas, peripheral nerve sheath tumors, multiple forms of cognitive dysfunction, and a higher risk of cancers such as pheochromocytoma and breast cancer in young women.…”

“…NF1 is a highly variable disease and considerable differences in clinical symptoms are noted within the same family [1]. Notably, phenotype-genotype correlation studies have suggested that the type of mutation in the NF1 gene does not solely account for the observed phenotype, with the exception of patients carrying chromosomal deletions (microdeletions) [6].…”