Genodermatoses 2003-2004.

Purpose of review Many genodermatoses have been linked in recent years to their respective genes. The underlying biology and integrative nature of these genes with other genes and organ systems is beginning to be understood. This paper reviews recent advances in neurocutaneous disorders, ectodermal dysplasias, and the phenomenon of revertant gene mosaicism. Recent findings In neurofibromatosis type 1, molecular assays are being developed to distinguish malignant from benign and premalignant lesions. Clinical mutation analysis for the NF1 gene has been problematic; a sensitive new assay using automated comparative sequence analysis may be helpful. Revision of clinical care guidelines is ongoing. New data for the prospective management of optic pathway gliomas is reviewed. The two genes that underlie tuberous sclerosis complex, tuberin and hamartin, lie at the center of an important signal transduction pathway with significant implications for pharmacologic treatment. Issues in genetic counseling for this highly variable disease are updated. Extensive progress has been made in understanding the basis of several forms of ectodermal dysplasia. Disorders caused by mutations in p63 and the connexin and NF-κB gene families will be reviewed. Finally, phenotypic in vivo amelioration of genodermatoses via revertant gene mosaicism will be discussed as a possible mechanism to be exploited in directed therapeutic approaches. Summary This paper reviews recent developments in the molecular and biologic bases of neurofibromatosis type 1, tuberous sclerosis, and ectodermal disorders related to p63 and the connexin and NF-κB gene families. The concept of revertant gene mosaicism is also discussed as a potential model for gene therapy.