Segmental manifestation of Darier disease - What is the genetic backgroundin type 1 and type 2 mosaic phenotypes?

Darier disease is an autosomal dominant disorder which may occasionally bec ome manifest in a segmental form. Two clinical phenotypes with a different genetic background have been elaborated in recent years. More than 50 patie nts with isolated linear disease expression have been documented. In this p henotype the skin outside the segmental affection is absolutely normal. Suc h a phenotype is explained by a postzygotic mutation with somatic mosaicism which was labeled as type 1 manifestation of segmental forms in autosomal skin disorders. A patient with classical type 1 segmental Darier disease is presented. On the other hand, only 3 patients with Darier disease showing a segmental manifestation in combination with a diffuse distribution have s o far been observed. These cases correspond to the recently described type 2 manifestation of segmental forms of autosomal dominant disorders. We desc ribe a fourth patient with type 2 segmental Darier disease. The genetic exp lanation of such a phenotype is possible with the assumption that a germlin e mutation for the disease exists but, in addition, a postzygotic mutation is needed resulting in loss of heterozygosity. Hence, in a circumscribed re gion a homozygous or hemizygous state of the mutation is apparent which can explain the enhanced severity of the segmental manifestation. Copyright (C ) 2000 S. Karger AG, Basel.