Kindler Syndrome - GeneReviews®

Acta Dermato-Venereologica, 2007

563 Letters to the Editor Sir, Kindler syndrome (KS) is a rare genodermatosis characterized by acral skin blistering and photosensitivity, followed by diffuse progressive poikiloderma, and various degrees of mucosal involvement (1). Mutations in the KIND1 gene (20p12.3) have been disclosed in most patients with clinical signs consistent with KS (2-4). The gene product, kindlin-1, is a 78-kDa phospho-protein expressed in skin in the basal keratinocytes (5). It forms complexes with β1 and β3 integrin subunits and, accordingly, kindlin-1-deficient keratinocytes have adhesion, proliferation, polarization and migration defects (6, 5). This report examines the genetic basis of KS in one Albanian and one Turkish patient with KS with severe involvement of the digestive and genitourinary mucosa, and discusses genotype/phenotype correlations.

Journal of Investigative Dermatology, 2015

Journal der Deutschen Dermatologischen Gesellschaft, 2018

International Journal of Dermatology, 2008

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.

Keywords Disease name/synonyms Definition/diagnostic criteria Differential Diagnosis Etiology Clinical description Diagnostic methods Management including treatment Kindler syndrome and epidermolysis bullosa Kindler syndrome and Weary's hereditary acrokeratotic poikiloderma References Abstract Kindler syndrome (KS) is a rare autosomal recessive genophotodermatosis. It combines features of acral blistering and photosensitivity from infancy, which tend to improve through childhood, with progressive poikiloderma and cutaneous atrophy developing later. Phenotypic heterogeneity and variable expression of the condition is known and additional features have been described. It shares some clinicopathologic similarities with dystrophic epidermolysis bullosa and Weary's hereditary acrokeratotic poikiloderma. However, characteristic immunohistochemical, ultrastructural and molecular features have been demonstrated which distinguish KS as a separate entity. Specifically, this condition has recently been shown to result from loss of function mutations in KIND1, the gene encoding kindlin-1, a novel protein involved in attachment of the actin cytoskeleton to the extracellular matrix via focal contacts.

Anais Brasileiros de Dermatologia, 2013

We report the case of a 28-year-old woman with Kindler syndrome, a rare form of epidermolysis bullosa. Clinically, since childhood, she had widespread pigmentary changes in her skin as well as photosensitivity and fragility of the skin and mucous membranes. The mucosal involvement led to an erosive stomatitis as well as esophageal, anal and vaginal stenoses, requiring surgical intervention. The diagnosis of Kindler syndrome was confirmed by DNA sequencing with compound heterozygosity for a nonsense/frameshift combination of mutations (p.Arg110X; p.Ala289GlyfsX7) in the FERMT1 gene.

Pediatric Dermatology, 2020

Kindler syndrome (OMIM 173650) was first described in 1954 by Theresa Kindler in a 14-year-old patient who presented with skin blistering, progressive poikiloderma, and diffuse and macular atrophy. Currently, it is considered an autosomal recessive subtype of epidermolysis bullosa. It is caused by mutations in the FERMT1 (formerly KIND1) gene (20p12.3), which encodes fermitin family homolog 1. This protein is involved in proliferation, cell-matrix adhesion, and migration in keratinocytes. 1,2 More than 80 pathogenic variants have been reported in the FERMT1 gene with a high prevalence of consanguinity among patients and recurrent mutations within ethnic groups. 3-6 Kindler syndrome is diagnosed by the presence of four major criteria, which include acral blistering in infancy and childhood, progressive poikiloderma, skin atrophy, abnormal photosensitivity, and gingival fragility. Additionally, minor criteria include pseudosyndactyly and mucosal involvement. Three major and two minor criteria make the diagnosis probable. Although skin blistering and photosensitivity tend to improve in adulthood, most patients will develop generalized poikiloderma,

Human Mutation, 2011

Mutations in the FERMT1 gene (also known as KIND1), encoding the focal adhesion protein kindlin-1, underlie the Kindler syndrome (KS), an autosomal recessive skin disorder with an intriguing progressive phenotype comprising skin blistering, photosensitivity, progressive poikiloderma with extensive skin atrophy, and propensity to skin cancer. Herein we review the clinical and genetic data of 62 patients, and delineate the natural history of the disorder, for example, age at onset of symptoms, or risk of malignancy. Although most mutations are predicted to lead to premature termination of translation, and to loss of kindlin-1 function, significant clinical variability is observed among patients. There is an association of FERMT1 missense and in-frame deletion mutations with milder disease phenotypes, and later onset of complications. Nevertheless, the clinical variability is not fully explained by genotype-phenotype correlations. Environmental factors and yet unidentified modifiers may play a role. Better understanding of the molecular pathogenesis of KS should enable the development of prevention strategies for disease complications.

Journal of Investigative Dermatology, 2004