Kindler Syndrome

Classification according to ICD-10
L13.8	Other specified bullous dermatoses
ICD-10 online (WHO version 2019)

Autosomal recessive inheritance

The Kindler syndrome is a rare autosomal recessive inherited skin disease (dermatosis), which is caused by a mutation of the gene Child1. The disease is also described in the literature as congenital bullous poikiloderma .

Like porphyria cutanea tarda , erythropoietic protoporphyria and actinic prurigo , the disease belongs to the group of photodermatoses .

Synonyms are: Acrokeratotic Poikiloderma; KS; Kindler type poikiloderma ; English POIKILODERMA, HEREDITARY ACROKERATOTIC; BULLOUS ACROKERATOTIC POIKILODERMA OF KINDLER AND WEARY; POIKILODERMA, CONGENITAL, WITH BULLAE, WEARY TYPE

The name refers to the first author of the first description from 1954 by the doctor Theresa Kindler .

Another description by P. Weary comes from 1971.

diagnosis

Blistering of the skin can be observed in newborns. Often hypo- or hyperpigmented skin is dry and slightly flaky. In addition, there are light sensitivity (photosensitivity), atrophy and fragility of the skin as well as adhesions of the mucous membranes and transitional mucous membranes . Patients already have periodontal disease in their youth . Mucosal erosions and fissures can be found in the anal and genital areas of the patient. Furthermore urethrastenosis and phimosis . In electron interruptions and branches of the basement membrane can be seen.

Incidence

Kindler syndrome is a very rare condition. Over 100 cases of the disease have been reported worldwide since Theresa Kindler was first described. A cluster of 26 patients with this syndrome was found in a tribe in the Bocas del Toro province on the northwestern Caribbean coast of Panama .

genetics

Kindler syndrome is caused by a mutation on chromosome 20 , gene locus 20p13. The C20orf42 gene (KIND1), which codes for the Kindlin-1 protein, also known as Kindlerin or Kindlin Syndrome protein , is located in this position . Kindlin 1 is an intracellular cytoskeleton linker protein made up of 677 amino acids .

The absence of the kindlin-1 protein in the skin leads to several changes in the basal keratinocytes : cell polarity is abolished, proliferation is significantly reduced and many cells are subject to apoptosis (programmed cell death).

Kindlin-1 is a homologue of the UNC-112 protein from the nematode Caenorhabditis elegans . This is a membrane-associated structural / signaling protein that plays an important role in connecting the actin of the cytoskeleton to the extracellular matrix .

forecast

The patients have a normal life expectancy. The blistering of the skin diminishes with age. However, the risk of developing skin cancer or carcinoma of the mucous membranes ( squamous cell carcinoma ) is significantly higher.

literature

• A. Hovnanian et al. a .: Poikiloderma of Theresa Kindler: report of a case with ultrastructural study, and review of the literature. In: Pediatric Dermatology . 6/1989, pp. 82-90. PMID 2664739
• RC Sharma et al. a .: Kindler syndrome. In: International Journal of Dermatology . 42/2003, pp. 727-732.
• E. Sadler et al. a .: Novel KIND1 gene mutation in Kindler syndrome with severe gastrointestinal tract involvement. In: Archives of Dermatology . 142/2006, pp. 1619-1624. PMID 17178989
• C. Has et al. a .: Molecular basis of Kindler syndrome in Italy: novel and recurrent Alu / Alu recombination, splice site, nonsense, and frameshift mutations in the KIND1 gene. In: Journal of Investigative Dermatology . 126/2006, pp. 1776-1783. PMID 16675959
• S. Kloeker u. a .: The Kindler syndrome protein is regulated by transforming growth factor-beta and involved in integrin-mediated adhesion. In: Journal of Biological Chemistry . 279/2004, pp. 6824-6833. PMID 14634021
• L. Lennartz, C. Has, P. Lehmann: Congenital bullous poikiloderma (Kindler syndrome) - new mutation. In: Journal of the German Dermatological Society Vol. 10, No. 12, December 2012, pp. 919-920, doi: 10.1111 / j.1610-0387.2012.08050.x , PMID 23078512 .
• C. Has: Kindler syndrome. A new bullous dermatosis. In: The dermatologist ; Journal of Dermatology, Venereology, and Allied Fields. Vol. 60, No. 8, August 2009, pp. 622-626, doi: 10.1007 / s00105-008-1676-y , PMID 19533072 (review).

Individual evidence

1. ↑ ^{a b} B. Binder u. a .: Congenital bullous poikilodermia (Kindler syndrome) In: The dermatologist. 53/2002, pp. 546-549.
2. ^ Kindler syndrome. In: Orphanet (Rare Disease Database).
3. ^ P. Poblete-Gutiérrez et al. a .: Hereditary photodermatoses. In: The dermatologist. 57/2006, pp. 1067-1082.
4. ↑ T. KINDLER: Congenital poikiloderma with traumatic bulla formation and progressive cutaneous atrophy. In: The British journal of dermatology. Vol. 66, No. 3, March 1954, pp. 104-111, PMID 13149722 .
5. ^ PE Weary, WF Manley, GF Graham: Hereditary acrokeratotic poikiloderma. In: Archives of dermatology. Vol. 103, No. 4, April 1971, pp. 409-422, PMID 4253719 .
6. ↑ Poikiloderma, akrokeratotische congenital, type Weary. In: Orphanet (Rare Disease Database).
7. ↑ genecards.org chromosome 20 open reading frame 42 , accessed March 22, 2008.
8. ↑ ^{a b c} Network Epidermolysis Bullosa: Kindler Syndrome ( Memento of the original from January 5, 2009 in the Internet Archive ) Info: The archive link was inserted automatically and not yet checked. Please check the original and archive link according to the instructions and then remove this notice. , accessed March 22, 2008. 
9. ↑ genecards.org Chromosomes 20
10. ^ Kindler syndrome.  In: Online Mendelian Inheritance in Man . (English)
11. ↑ C. Herz u. a .: Kindlin-1 is a phosphoprotein involved in regulation of polarity, proliferation, and motility of epidermal keratinocytes. In: J Biol Chem . 281/2006, pp. 36082-36090. PMID 17012746 .
12. ↑ DH Siegel u. a .: Loss of kindlin-1, a human homolog of the Caenorhabditis elegans actin-extracellular-matrix linker protein UNC-112, causes Kindler syndrome. In: Am J Hum Genet. 174/2003, pp. 174-187. PMID 12789646
13. ↑ GH Ashton et al. a .: Recurrent mutations in kindlin-1, a novel keratinocyte focal contact protein, in the autosomal recessive skin fragility and photosensitivity disorder, Kindler syndrome. In: Journal of Investigative Dermatology. 2004, Vol. 122, pp. 78-83. PMID 14962093 .

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