[How frequently does genetic mosaicism occur in the skin?]. / Wie häufig sind genetische Mosaike in der Haut?

BACKGROUND: Until recently, cutaneous mosaicism was considered a rare phenomenon. Its practical significance was considered minimal. OBJECTIVES: The following questions will be considered: How often are mosaic skin disorders seen in dermatological practice? In which ways can special dermatological competence contribute to assure an appropriate genetic counseling? METHODS: This review is based on the analysis of recent research articles and on the author's book "Mosaicism in Human Skin" (Berlin, Springer 2014). RESULTS: The following categories can be distinguished: punctual versus disseminated mosaicism; segmental manifestation of lethal autosomal mutations; type 1 versus type 2 segmental involvement in autosomal dominant skin disorders; isolated versus superimposed manifestation of polygenic skin disorders; twin spotting; epigenetic mosaicism; revertant mosaicism. CONCLUSIONS: Cutaneous mosaicism occurs so frequently that dermatologists can note it every day in their practice, usually in the form of punctual mosaicism. In the group of autosomal dominant genodermatoses, the type 1 segmental manifestation implies a slightly increased risk that the disorder will affect the patient's offspring in a diffuse form, whereas in cases of type 2 segmental involvement this risk is 50%. In the group of common skin disorders with a polygenic background, cellular analysis of a superimposed segmental manifestation may contribute to elucidate the genetic basis of such diseases. In the group of epigenetically controlled functional mosaics of the skin, we discriminate between X-linked and autosomal forms that are always inheritable. From the concept of revertant mosaicism, a new approach to treat severe genodermatoses can perhaps be developed.

Loss of Kindlin-1 causes skin atrophy and lethal neonatal intestinal epithelial dysfunction.

Kindler Syndrome (KS), characterized by transient skin blistering followed by abnormal pigmentation, skin atrophy, and skin cancer, is caused by mutations in the FERMT1 gene. Although a few KS patients have been reported to also develop ulcerative colitis (UC), a causal link to the FERMT1 gene mutation is unknown. The FERMT1 gene product belongs to a family of focal adhesion proteins (Kindlin-1, -2, -3) that bind several beta integrin cytoplasmic domains. Here, we show that deleting Kindlin-1 in mice gives rise to skin atrophy and an intestinal epithelial dysfunction with similarities to human UC. This intestinal dysfunction results in perinatal lethality and is triggered by defective intestinal epithelial cell integrin activation, leading to detachment of this barrier followed by a destructive inflammatory response.

Kindler syndrome: a study of five Egyptian cases with evaluation of severity.

BACKGROUND: Kindler syndrome (KS) is a rare genodermatosis characterized by four major features (acral blisters, photosensitivity, poikiloderma, and cutaneous atrophy) and many associated findings. The diagnosis of KS includes clinical features, ultrastructural findings, and, recently, immunostaining and genetic studies. Varying degrees of severity of the syndrome have been described. METHODS: Five patients with clinical features consistent with KS were included in this study. All patients were subjected to histopathologic and ultrastructural studies. RESULTS: Cases 1 and 2 presented with severe major features, severe mucosal involvement, and many other associated findings. Case 3 presented with severe major features, but mild and limited mucosal involvement and other associated findings. Cases 4 and 5 showed mild major features and few other findings. Histopathology revealed nonspecific poikiloderma. Marked thickening of the lamina densa and splitting of the lamina lucida were the main ultrastructural findings. CONCLUSION: KS may be classified into mild, moderate, and severe according to the severity of the major features and mucosal involvement. Because histopathologic and ultrastructural findings are not pathognomonic, clinical features remain the mainstay for the diagnosis of KS, and the need for immunostaining with kindlin antibody and genetic studies may be restricted to early cases with incomplete features.