Segmental forms of autosomal dominant skin disorders: The puzzle of mosaicism

Autosomal dominant inherited disorders of the skin sometimes present as a s egmental phenotype. In recent years molecular studies have demonstrated tha t genetic mosaicism leads to such a clinical manifestation. In general the skin outside the segmental disorder is normal. This rather common variant o f segmental manifestation has been termed type 1. Recently, Happle delineat ed a second type of segmental manifestation of autosomal dominant genoderma tosis. This variant is characterized by a more diffuse clinical presentatio n of the disease, and a very marked linear pattern can be recognized. An ex planation of this phenotype is a germline mutation of the gene manifests af ter a postzygotic mutation leading to double inactivation of the gene. The severe linear manifestation then reflects a doubling of the genetic burden. We present a number of clinical cases to demonstrate this phenomenon, and we present a case of the segmental Naegeli-Franceschetti-Jadassohn syndrome born to a mother with the diffuse manifestation of the disorder. (C) 1999 Wiley-Liss, Inc.