Genetic skin diseases

Recent advances in molecular genetics have led to major breakthroughs in the understanding of two heterogeneous groups of inherited skin diseases, epidermolysis bullosa and the ichthyoses. Mutations in keratins K5 or K14 are found in epidermolysis bullosa simplex. The gravis (Herlitz) variety of junctional epidermolysis bullosa is characterized by defects in the anchoring filament protein kalinin. Both dominant and recessive forms of dystrophic epidermolysis bullosa appear to be due to mutations in the type VII collagen gene. Biochemical studies in patients with ichthyosis vulgaris reveal that the proteins profilaggrin and filaggrin are reduced or absent. Recessive X-linked ichthyosis is characterized by a deficiency of the enzyme steroid sulfatase. A type of lamellar ichthyosis may be explained on the basis of abnormal cornified cell envelope formation, and bullous congenital ichthyosiform erythroderma (epidermolytic hyperkeratosis) is caused by mutations in keratins K1 or K10.