[Segmental type 2 manifestation of autosome dominant skin diseases. Development of a new formal genetic concept].

The prevailing theory says that mosaic forms of autosomal dominant skin diseases originate from postzygotic new mutations. This theory is no longer generally valid. According to a new rule of dichotomy, we can distinguish two types of segmental manifestations. The type 1 reflects heterozygosity for a postzygotic new mutation, whereas the type 2 results from loss of the corresponding wildtype allele occurring in a heterozygous embryo and reflects either homozygosity or hemizygosity for the underlying mutation, giving rise to rather pronounced segmental lesions that are superimposed on the ordinary nonsegmental phenotype. Autosomal dominant skin diseases exemplifying the concept of type 2 segmental manifestation so far include neurofibromatosis 1, tuberous sclerosis, cutaneous leiomyomatosis, glomangiomatosis, Buschke-Ollendorff syndrome, multiple syringomas, multiple trichoepitheliomas, multiple basaloid follicular hamartomas, multiple nevoid basal cell carcinomas, Darier disease, Hailey-Hailey disease, epidermolytic hyperkeratosis of Brocq, KID syndrome, disseminated superficial actinic porokeratosis and autosomal dominant dyskeratosis congenita. A strikingly high frequency of type 2 segmental involvement has been documented in cutaneous leiomyomatosis, glomangiomatosis and disseminated superficial actinic porokeratosis. It should be noted that there is so far no molecular proof for the proposed rule of dichotomy that has been developed from clinical dermatology. According to present knowledge, however, it is very likely that molecular analysis will confirm the described concept that can explain some so far enigmatic features as observed in autosomal dominant genodermatoses.