Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Kindler syndrome

Cristina Has, MD
Section Editor
Jennifer L Hand, MD
Deputy Editor
Rosamaria Corona, MD, DSc


Kindler syndrome (KS, MIM# 173650), also known as Weary-Kindler syndrome, is a rare autosomal recessive type of epidermolysis bullosa characterized by skin blistering, photosensitivity, progressive poikiloderma (the combination of skin atrophy, telangiectasias, and pigmentary changes), extensive skin atrophy, and squamous cell carcinomas of skin and mucosal membranes. It was first described in 1954 by Theresa Kindler and considered a poikilodermatous disorder until 2008, when it was classified as a distinct type of epidermolysis bullosa [1]. As the first genetic cutaneous disorder associated with alterations in a protein of focal adhesions, KS and its pathogenesis became an important model for understanding the role of focal adhesions in the skin.

This topic will discuss the pathogenesis, clinical features, diagnosis, and management of Kindler syndrome. Other types of inherited epidermolysis bullosa are discussed separately.

(See "Epidemiology, pathogenesis, classification, and clinical features of epidermolysis bullosa".)

(See "Diagnosis of epidermolysis bullosa".)

(See "Overview of the management of epidermolysis bullosa".)

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Nov 2017. | This topic last updated: Jun 22, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Fine JD, Bruckner-Tuderman L, Eady RA, et al. Inherited epidermolysis bullosa: updated recommendations on diagnosis and classification. J Am Acad Dermatol 2014; 70:1103.
  2. Penagos H, Jaen M, Sancho MT, et al. Kindler syndrome in native Americans from Panama: report of 26 cases. Arch Dermatol 2004; 140:939.
  3. Youssefian L, Vahidnezhad H, Barzegar M, et al. The Kindler syndrome: a spectrum of FERMT1 mutations in Iranian families. J Invest Dermatol 2015; 135:1447.
  4. Jobard F, Bouadjar B, Caux F, et al. Identification of mutations in a new gene encoding a FERM family protein with a pleckstrin homology domain in Kindler syndrome. Hum Mol Genet 2003; 12:925.
  5. Siegel DH, Ashton GH, Penagos HG, 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; 73:174.
  6. Zhan J, Yang M, Zhang J, et al. Kindler syndrome protein Kindlin-1 is mainly expressed in adult tissues originating from ectoderm/endoderm. Sci China Life Sci 2015; 58:432.
  7. Petricca G, Leppilampi M, Jiang G, et al. Localization and potential function of kindlin-1 in periodontal tissues. Eur J Oral Sci 2009; 117:518.
  8. Herz C, Aumailley M, Schulte C, et al. Kindlin-1 is a phosphoprotein involved in regulation of polarity, proliferation, and motility of epidermal keratinocytes. J Biol Chem 2006; 281:36082.
  9. Kern JS, Herz C, Haan E, et al. Chronic colitis due to an epithelial barrier defect: the role of kindlin-1 isoforms. J Pathol 2007; 213:462.
  10. Karaköse E, Schiller HB, Fässler R. The kindlins at a glance. J Cell Sci 2010; 123:2353.
  11. Margadant C, Kreft M, Zambruno G, Sonnenberg A. Kindlin-1 regulates integrin dynamics and adhesion turnover. PLoS One 2013; 8:e65341.
  12. Patel H, Stavrou I, Shrestha RL, et al. Kindlin1 regulates microtubule function to ensure normal mitosis. J Mol Cell Biol 2016; 8:338.
  13. Qu H, Wen T, Pesch M, Aumailley M. Partial loss of epithelial phenotype in kindlin-1-deficient keratinocytes. Am J Pathol 2012; 180:1581.
  14. Shen C, Sun L, Zhu N, Qi F. Kindlin-1 contributes to EGF-induced re-epithelialization in skin wound healing. Int J Mol Med 2017; 39:949.
  15. Patel H, Zich J, Serrels B, et al. Kindlin-1 regulates mitotic spindle formation by interacting with integrins and Plk-1. Nat Commun 2013; 4:2056.
  16. Rognoni E, Widmaier M, Jakobson M, et al. Kindlin-1 controls Wnt and TGF-β availability to regulate cutaneous stem cell proliferation. Nat Med 2014; 20:350.
  17. Zhang X, Luo S, Wu J, et al. KIND1 Loss Sensitizes Keratinocytes to UV-Induced Inflammatory Response and DNA Damage. J Invest Dermatol 2017; 137:475.
  18. Maier K, He Y, Wölfle U, et al. UV-B-induced cutaneous inflammation and prospects for antioxidant treatment in Kindler syndrome. Hum Mol Genet 2016; 25:5339.
  19. Maier K, He Y, Esser PR, et al. Single Amino Acid Deletion in Kindlin-1 Results in Partial Protein Degradation Which Can Be Rescued by Chaperone Treatment. J Invest Dermatol 2016; 136:920.
  20. Emmert H, Patel H, Brunton VG. Kindlin-1 protects cells from oxidative damage through activation of ERK signalling. Free Radic Biol Med 2017; 108:896.
  21. Heinemann A, He Y, Zimina E, et al. Induction of phenotype modifying cytokines by FERMT1 mutations. Hum Mutat 2011; 32:397.
  22. Techanukul T, Sethuraman G, Zlotogorski A, et al. Novel and recurrent FERMT1 gene mutations in Kindler syndrome. Acta Derm Venereol 2011; 91:267.
  23. Has C, Ludwig RJ, Herz C, et al. C-terminally truncated kindlin-1 leads to abnormal adhesion and migration of keratinocytes. Br J Dermatol 2008; 159:1192.
  24. Has C, Chmel N, Levati L, et al. FERMT1 promoter mutations in patients with Kindler syndrome. Clin Genet 2015; 88:248.
  25. Chmel N, Danescu S, Gruler A, et al. A Deep-Intronic FERMT1 Mutation Causes Kindler Syndrome: An Explanation for Genetically Unsolved Cases. J Invest Dermatol 2015; 135:2876.
  26. Fuchs-Telem D, Nousbeck J, Singer A, et al. New intragenic and promoter region deletion mutations in FERMT1 underscore genetic homogeneity in Kindler syndrome. Clin Exp Dermatol 2014; 39:361.
  27. Krishna CV, Parmar NV, Has C. Kindler syndrome with severe mucosal involvement in childhood. Clin Exp Dermatol 2014; 39:340.
  28. El Hachem M, Diociaiuti A, Proto V, et al. Kindler syndrome with severe mucosal involvement in a large Palestinian pedigree. Eur J Dermatol 2015; 25:14.
  29. Wiebe CB, Petricca G, Häkkinen L, et al. Kindler syndrome and periodontal disease: review of the literature and a 12-year follow-up case. J Periodontol 2008; 79:961.
  30. Wiebe CB, Penagos H, Luong N, et al. Clinical and microbiologic study of periodontitis associated with Kindler syndrome. J Periodontol 2003; 74:25.
  31. Has C, Castiglia D, del Rio M, et al. Kindler syndrome: extension of FERMT1 mutational spectrum and natural history. Hum Mutat 2011; 32:1204.
  32. Shimizu S, Nishie W, Tsuchiya K, et al. Kindler syndrome with severe intestinal involvement: a 31-year follow-up. Acta Derm Venereol 2014; 94:351.
  33. Mansur AT, Elcioglu NH, Aydingöz IE, et al. Novel and recurrent KIND1 mutations in two patients with Kindler syndrome and severe mucosal involvement. Acta Derm Venereol 2007; 87:563.
  34. Ezzine Sebaï N, Trojjet S, Khaled A, et al. [Kindler syndrome: three cases reports in three siblings]. Ann Dermatol Venereol 2007; 134:774.
  35. Hayashi S, Shimoya K, Itami S, Murata Y. Pregnancy and delivery with Kindler syndrome. Gynecol Obstet Invest 2007; 64:72.
  36. Lelli GJ Jr. Kindler syndrome causing severe cicatricial ectropion. Ophthal Plast Reconstr Surg 2010; 26:368.
  37. Arita K, Wessagowit V, Inamadar AC, et al. Unusual molecular findings in Kindler syndrome. Br J Dermatol 2007; 157:1252.
  38. Lai-Cheong JE, Moss C, Parsons M, et al. Revertant mosaicism in Kindler syndrome. J Invest Dermatol 2012; 132:730.
  39. Kiritsi D, He Y, Pasmooij AM, et al. Revertant mosaicism in a human skin fragility disorder results from slipped mispairing and mitotic recombination. J Clin Invest 2012; 122:1742.
  40. Pasmooij AM, Jonkman MF, Uitto J. Revertant mosaicism in heritable skin diseases: mechanisms of natural gene therapy. Discov Med 2012; 14:167.
  41. Hintner H, Stingl G, Schuler G, et al. Immunofluorescence mapping of antigenic determinants within the dermal-epidermal junction in the mechanobullous diseases. J Invest Dermatol 1981; 76:113.
  42. Pohla-Gubo G, Cepeda-Valdes R, Hintner H. Immunofluorescence mapping for the diagnosis of epidermolysis bullosa. Dermatol Clin 2010; 28:201.
  43. Has C, He Y. Research Techniques Made Simple: Immunofluorescence Antigen Mapping in Epidermolysis Bullosa. J Invest Dermatol 2016; 136:e65.
  44. Lai-Cheong JE, McGrath JA. Kindler syndrome. Dermatol Clin 2010; 28:119.
  45. Has C, Kiritsi D, Mellerio JE, et al. The missense mutation p.R1303Q in type XVII collagen underlies junctional epidermolysis bullosa resembling Kindler syndrome. J Invest Dermatol 2014; 134:845.
  46. Larizza L, Roversi G, Volpi L. Rothmund-Thomson syndrome. Orphanet J Rare Dis 2010; 5:2.
  47. Koparir A, Gezdirici A, Koparir E, et al. Poikiloderma with neutropenia: genotype-ethnic origin correlation, expanding phenotype and literature review. Am J Med Genet A 2014; 164A:2535.
  48. Van Hove JL, Jaeken J, Proesmans M, et al. Clericuzio type poikiloderma with neutropenia is distinct from Rothmund-Thomson syndrome. Am J Med Genet A 2005; 132A:152.
  49. Arnold AW, Itin PH, Pigors M, et al. Poikiloderma with neutropenia: a novel C16orf57 mutation and clinical diagnostic criteria. Br J Dermatol 2010; 163:866.
  50. Mostefai R, Morice-Picard F, Boralevi F, et al. Poikiloderma with neutropenia, Clericuzio type, in a family from Morocco. Am J Med Genet A 2008; 146A:2762.
  51. Volpi L, Roversi G, Colombo EA, et al. Targeted next-generation sequencing appoints c16orf57 as clericuzio-type poikiloderma with neutropenia gene. Am J Hum Genet 2010; 86:72.
  52. Has C, Burger B, Volz A, et al. Mild clinical phenotype of Kindler syndrome associated with late diagnosis and skin cancer. Dermatology 2010; 221:309.
  53. El Hachem M, Zambruno G, Bourdon-Lanoy E, et al. Multicentre consensus recommendations for skin care in inherited epidermolysis bullosa. Orphanet J Rare Dis 2014; 9:76.
  54. Krämer SM, Serrano MC, Zillmann G, et al. Oral health care for patients with epidermolysis bullosa--best clinical practice guidelines. Int J Paediatr Dent 2012; 22 Suppl 1:1.
  55. Figueira EC, Murrell DF, Coroneo MT. Ophthalmic involvement in inherited epidermolysis bullosa. Dermatol Clin 2010; 28:143.
  56. Mellerio JE, Robertson SJ, Bernardis C, et al. Management of cutaneous squamous cell carcinoma in patients with epidermolysis bullosa: best clinical practice guidelines. Br J Dermatol 2016; 174:56.