Case of Kindler syndrome resulting from mutation in the FERMT1 gene

Dear Editor, Kindler syndrome (KS), first reported in 1954 by Dr Theresa Kindler, is characterized clinically by trauma-induced skin blistering, skin atrophy, poikiloderma and varying degrees of photosensitivity, and histopathologically by a plane of cleavage close to the dermoepidermal junction. Pathogenesis of KS is mutation in the FERMT1 gene that encodes fermitin family homolog-1, kindlin-1, an actin cytoskeleton and focal adhesion-associated molecule. A 49-year-old Japanese woman presented with a history of recurrent blistering on her extremities after mild trauma from the age of 1 year. She also suffered from photosensitivity. At the age of 10 years, she was diagnosed with epidermolysis bullosa. She had been carefully followed up. At the age of 48 years, because of ocular pain, she was referred to our hospital for further examinations. Her parents were first cousins and other members of the family were healthy. She had no past history. Physical examination revealed reticular pigmentation on her cheek, erosion on the lip and gingivitis (Fig. 1a). Skin wrinkling on the elbow, and scarring and atrophy on her forearm were present. Both hands showed progressive poikiloderma and skin atrophy on the dorsal aspect (Fig. 1b). Both palms showed mild hyperkeratosis and scaling. In addition, finger webbing and pseudosyndactyly were present. Ophthalmic examination revealed corneal erosion. A skin biopsy was taken from her left forearm after mild rubbing with an eraser. Electron microscopic findings showed widening of the lamina lucida, reduplication of the lamina densa and amorphous materials in the area of sub-lamina densa (Fig. 2a). Most interestingly, widening of the lamina lucida was observed at the points where hemidesmosomes were not observed. We then performed immunofluorescent examinations. The expression of type VII collagen showed a broad, reticulate labeling pattern (Fig. 2b), whereas that of hemidesmosome components, including a6-integrin, b4-integrin, BP180 and plectin, showed a normal bright linear pattern and that of keratin-5 and keratin-14 showed a bright filamentous pattern (data not shown). Additionally, we performed an immunofluorescent study using anti-kindlin-1 antibody (kindly provided by Dr Mary Beckarle), which recognizes the C-terminal region of kindlin-1 protein. In a control skin section, kindlin-1 staining showed a liner and cell surface pattern in the basal keratinocytes (Fig. 2c). In sharp contrast, no expression was observed in the patient skin section (Fig. 2d). Finally, genetic analysis of the FERMT1 gene was performed. The result revealed a homozygous mutation at c.1089delG (Fig. 2e). We diagnosed the patient as having KS. (a)