- Author: Anatoli Freiman, MD, FRCPC, DABD; Chief Editor: Dirk M Elston, MD more...
Kindler syndrome was first described in 1954 by Theresa Kindler. Kindler syndrome is a rare autosomal recessive genodermatosis characterized by congenital acral skin blistering, photosensitivity, progressive poikiloderma, and diffuse cutaneous atrophy. The syndrome is a combination of features of inherited blistering skin disorders (eg, dystrophic epidermolysis bullosa) and congenital poikilodermas (eg, Rothmund-Thompson syndrome). Kindler syndrome is identified as entry 173650 in the Online Mendelian Inheritance of Man database. Note the image set below.
In 2003, Siegel et al mapped the disease locus to band 20p12.3 by using linkage and homozygosity analysis in an isolated cohort of patients with Kindler syndrome. Loss-of-function mutations were identified in the candidate gene FLJ20116, which was renamed KIND1. This gene encodes a 677–amino acid protein, kindlin-1, which is thought to play a regulatory role in inhibiting oversecretion of basement membrane components by basal keratinocytes at the dermoepidermal junction.[2, 3]
Kindlin-1 is a human homolog of the Caenorhabditis elegans protein UNC-112, a membrane-associated structural/signaling protein that had been implicated in linking the actin cytoskeleton to the extracellular matrix (ECM). Kindler syndrome is the first genodermatosis caused by a defect in actin-ECM linkage rather than keratin-ECM linkage, underlying the pathology of other inherited skin fragility disorders such as epidermolysis bullosa.
Since the first description in 1954 by Theresa Kindler, more than 100 cases of Kindler syndrome have been reported worldwide. A cluster of 26 patients with the syndrome has been identified within a tribe in the Bocas del Toro province on the northwestern Caribbean coast of Panama.
Persons of any race can be affected.
No sex predilection has been documented.
Patients usually present with the initial skin manifestations during the first year of life.
Siegel DH, Ashton GH, Penagos HG, Lee JV, Feiler HS, Wilhelmsen KC, et al. Loss of kindlin-1, a human homolog of the Caenorhabditis elegans actin-extracellular-matrix linker protein UNC-112, causes Kindler syndrome. Am J Hum Genet. 2003 Jul. 73(1):174-87. [Medline].
Ashton GH, McLean WH, South AP, Oyama N, Smith FJ, Al-Suwaid R, et al. Recurrent mutations in kindlin-1, a novel keratinocyte focal contact protein, in the autosomal recessive skin fragility and photosensitivity disorder, Kindler syndrome. J Invest Dermatol. 2004 Jan. 122(1):78-83. [Medline].
Lai-Cheong JE, Ussar S, Arita K, Hart IR, McGrath JA. Colocalization of kindlin-1, kindlin-2, and migfilin at keratinocyte focal adhesion and relevance to the pathophysiology of Kindler syndrome. J Invest Dermatol. 2008 Sep. 128(9):2156-65. [Medline].
Penagos H, Jaen M, Sancho MT, Saborio MR, Fallas VG, Siegel DH, et al. Kindler syndrome in native Americans from Panama: report of 26 cases. Arch Dermatol. 2004 Aug. 140(8):939-44. [Medline].
Wiebe CB, Penagos H, Luong N, Slots J, Epstein E Jr, Siegel D, et al. Clinical and microbiologic study of periodontitis associated with Kindler syndrome. J Periodontol. 2003 Jan. 74(1):25-31. [Medline].
Shimizu H, Sato M, Ban M, Kitajima Y, Ishizaki S, Harada T, et al. Immunohistochemical, ultrastructural, and molecular features of Kindler syndrome distinguish it from dystrophic epidermolysis bullosa. Arch Dermatol. 1997 Sep. 133(9):1111-7. [Medline].
Burch JM, Fassihi H, Jones CA, Mengshol SC, Fitzpatrick JE, McGrath JA. Kindler syndrome: a new mutation and new diagnostic possibilities. Arch Dermatol. 2006 May. 142(5):620-4. [Medline].
Ashton GH. Kindler syndrome. Clin Exp Dermatol. 2004 Mar. 29(2):116-21. [Medline].
D'Souza MA, Kimble RM, McMillan JR. Kindler syndrome pathogenesis and fermitin family homologue 1 (kindlin-1) function. Dermatol Clin. 2010 Jan. 28(1):115-8. [Medline].