Genetics of neurocutaneous disorders

Abstract

Introduction Neurocutaneous disorders in humans affect both the nervous system and the skin. Developmentally, both the skin and nervous system arise from embryonic ectoderm. There are more than 40 such disorders described in this text, with the majority displaying Mendelian inheritance. Mendelian inheritance refers to so-called ‘single gene’ conditions; conditions that have a specific clinical picture (phenotype) based on mutation of one gene. All the many facets of a disease and the multitude of differences between one affected person and another cannot be attributed entirely to the action of a single gene. There are modifier genes that influence phenotype as well as environmental conditions. ‘Single gene’ conditions are sometimes genetically heterogeneous; mutations in different genes can result in similar (often indistinguishable) phenotypes. Many of the neurocutaneous diseases exhibit variable phenotypes due to different mutations in a single gene (e.g. the proto-oncogene RET in multiple endocrine neoplasia type 2B (MEN2B), or the ATP-binding cassette C6 gene (ABCC6) in Pseudoxanthoma elasticum ) while others have very similar phenotypes that result from mutations at different genetic loci (e.g. the Osler–Rendu–Weber syndromes and tuberous sclerosis complex). Disease-causing mutations in the causative genes have been identified for many of the neurocutaneous disorders during the past 15 years as a result of the rapid technologic advances in gene hunting. This chapter is devoted to discussing the hereditary patterns and causative genes. Inheritance patterns The hereditary influence on the traits of living organisms mainly resides in the chemical information of the nucleic acids (genes) of the organism.