|Disease group||Epithelial adhesion disorders|
|DISEASE NAME||KINDLER SYNDROME|
|Gene (s)||KIND1 (607900)|
Kindler syndrome is a rare autosomal recessive genodermatosis characterized by congenital skin blistering, mild photosensitivity and progressive poikiloderma with extensive skin atrophy.
The clinical features of Kindler syndrome include congenital skin blistering and mild photosensitivity both of which improve with age, and an early, generalized, progressive poikiloderma with extensive skin atrophy. The presence of palmoplantar keratoderma and nail abnormalities is variable; webbing of the fingers and contractures may also occur. Gingival fragility, poor dentition, as well as early and rapidly progressive periodontitis occur in some patients. Other mucous membranes, i.e. urethral, anal, oesophageal and genital mucosae may be involved and the lesions can lead to stenosis. Squamous cell carcinomas have been reported as complications of Kindler syndrome.
Kindler syndrome is caused by mutations in the KIND1 gene localized in the short arm of chromosome 20. The Kindlin protein is part of the focal contacts. Histology of skin shows epidermal atrophy, focal vacuolization of basal keratinocytes and pigmentary incontinence in the upper dermis. Electron microscopy shows reduplication of the epidermal basement membrane and the different levels of blister formation.
Careful investigation of the family history, clinical examination of the entire skin surface, of the nails, hair, dentition and mucosal surfaces must be performed systematically (see fig. 1).
Figure 1. Diagnostic algorithm for epithelial adhesion disorders (modified form www.netzwerk-eb.de)
The morphological analysis of a skin biopsy is the essential step in the diagnostic algorithm. These analyses reveal the level of the skin split and sometimes indicate the defective skin structure or the defective protein. In Kindler syndrome antigen mapping demonstrates abnormal and discontinuous staining patterns of laminin 332 (previously laminin 5), α6-, ß4-integrin and collagens XVII and VII. Microbiological and serological tests exclude primary or secondary infections and autoimmune diseases as a cause for skin blistering. Mutation detection is reasonable if the family requests genetic counseling and prenatal diagnosis for further pregnancies.
There is no causal therapy known. Symptomatic therapy comprises a high standard of personal hygiene and daily skin care, protection from trauma and avoidance of infections. Blisters should be burst with a sterile needle, erosive skin areas should be disinfected and dressings should be used that do not cause friction. Patients should use sun protection. Patient care requires multidisciplinary management and collaboration of pediatricians, dermatologists, gastroenterologists, dentists, plastic surgeons, nutritionists and psychologists.