Kindler Syndrome 

  • Author: Anatoli Freiman, MD, FRCPC, DABD; Chief Editor: Dirk M Elston, MD   more...
 
Updated: Jun 18, 2010
 

Background

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.

Images show the progression of lesions. A and B: AImages show the progression of lesions. A and B: At birth, acral blisters and erosions are present. C and D: At age 5 years, atrophy and reticulated erythema with dyschromic patches are noted. E and F: At age 7 years, progressive poikilodermatous changes with reticulated erythema and telangiectasia occur. G and H: At age 10 and 15 years, poikiloderma with telangiectasia and depigmentation are observed. Excoriations are due to pruritus. Reprinted from Yasukawa K, Sato-Matsumura KC, McMillan J, et al: Exclusion of COL7A1 mutation in Kindler syndrome. J Am Acad Dermatol 2002 Mar; 46(3): 447-50. Courtesy of the American Academy of Dermatology.
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Pathophysiology

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.[1] 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.

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Epidemiology

Frequency

International

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.[4]

Mortality/Morbidity

Morbidity and mortality are mostly related to secondary infections arising from cutaneous bullae and to cosmetic disfigurement.

Race

Persons of any race can be affected.

Sex

No sex predilection has been documented.

Age

Patients usually present with the initial skin manifestations during the first year of life.

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Contributor Information and Disclosures
Author

Anatoli Freiman, MD, FRCPC, DABD  Consulting Staff, Division of Dermatology, Women's College Hospital, University of Toronto

Anatoli Freiman, MD, FRCPC, DABD is a member of the following medical societies: American Academy of Dermatology, American Society for Dermatologic Surgery, Canadian Dermatology Association, Canadian Medical Association, Ontario Medical Association, Royal College of Physicians and Surgeons of Canada, and Women's Dermatologic Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Franklin Flowers, MD  Chief, Division of Dermatology, Professor, Department of Medicine and Otolaryngology, Affiliate Associate Professor of Pediatrics and Pathology, University of Florida College of Medicine

Franklin Flowers, MD, is a member of the following medical societies: American College of Mohs Micrographic Surgery and Cutaneous Oncology

Disclosure: Nothing to disclose.

David F Butler, MD  Professor of Dermatology, Texas A&M University College of Medicine; Chair, Department of Dermatology, Director, Dermatology Residency Training Program, Scott and White Clinic, Northside Clinic

David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Robert A Schwartz, MD, MPH  Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and Sigma Xi

Disclosure: Nothing to disclose.

Catherine M Quirk, MD  Clinical Assistant Professor, Department of Dermatology, University of Pennsylvania

Catherine M Quirk, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD  Director, Department of Dermatology, Geisinger Medical Center

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

References

  1. 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. Jul 2003;73(1):174-87. [Medline].

  2. 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. Jan 2004;122(1):78-83. [Medline].

  3. 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. Sep 2008;128(9):2156-65. [Medline].

  4. 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. Aug 2004;140(8):939-44. [Medline].

  5. 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. Jan 2003;74(1):25-31. [Medline].

  6. 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. Sep 1997;133(9):1111-7. [Medline].

  7. Burch JM, Fassihi H, Jones CA, Mengshol SC, Fitzpatrick JE, McGrath JA. Kindler syndrome: a new mutation and new diagnostic possibilities. Arch Dermatol. May 2006;142(5):620-4. [Medline].

  8. Ashton GH. Kindler syndrome. Clin Exp Dermatol. Mar 2004;29(2):116-21. [Medline].

  9. D'Souza MA, Kimble RM, McMillan JR. Kindler syndrome pathogenesis and fermitin family homologue 1 (kindlin-1) function. Dermatol Clin. Jan 2010;28(1):115-8. [Medline].

  10. Haber RM, Hanna WM. Kindler syndrome. Clinical and ultrastructural findings. Arch Dermatol. Dec 1996;132(12):1487-90. [Medline].

  11. Has C, Wessagowit V, Pascucci M, Baer C, Didona B, Wilhelm C, et al. Molecular basis of Kindler syndrome in Italy: novel and recurrent Alu/Alu recombination, splice site, nonsense, and frameshift mutations in the KIND1 gene. J Invest Dermatol. Aug 2006;126(8):1776-83. [Medline].

  12. Has C, Yordanova I, Balabanova M, Kazandjieva J, Herz C, Kohlhase J, et al. A novel large FERMT1 (KIND1) gene deletion in Kindler syndrome. J Dermatol Sci. Dec 2008;52(3):209-12. [Medline].

  13. Hovnanian A, Blanchet-Bardon C, de Prost Y. Poikiloderma of Theresa Kindler: report of a case with ultrastructural study, and review of the literature. Pediatr Dermatol. Jun 1989;6(2):82-90. [Medline].

  14. Jobard F, Bouadjar B, Caux F, Hadj-Rabia S, Has C, Matsuda 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. Apr 15 2003;12(8):925-35. [Medline].

  15. [Best Evidence] Lai-Cheong JE, McGrath JA. Kindler syndrome. Dermatol Clinics. Jan;28(1):119--24. [Medline].

  16. [Best Evidence] Lai-Cheong JE, Tanaka A, Hawche G, Emanuel P, Maari C, Taskesen M, et al. Kindler syndrome: a focal adhesion genodermatosis. Br J Dermatol. Feb 2009;160(2):233-42. [Medline].

  17. Lanschuetzer CM, Muss WH, Emberger M, Pohla-Gubo G, Klausegger A, Bauer JW, et al. Characteristic immunohistochemical and ultrastructural findings indicate that Kindler's syndrome is an apoptotic skin disorder. J Cutan Pathol. Oct 2003;30(9):553-60. [Medline].

  18. Patrizi A, Pauluzzi P, Neri I, Trevisan G, De Giorgi LB, Pasquinelli G. Kindler syndrome: report of a case with ultrastructural study and review of the literature. Pediatr Dermatol. Sep-Oct 1996;13(5):397-402. [Medline].

  19. Senturk N, Usubutun A, Sahin S, Bukulmez G, Erkek E, Topaloglu R, et al. Kindler syndrome: absence of definite ultrastructural feature. J Am Acad Dermatol. Feb 1999;40(2 Pt 2):335-7. [Medline].

  20. Sharma RC, Mahajan V, Sharma NL, Sharma AK. Kindler syndrome. Int J Dermatol. Sep 2003;42(9):727-32. [Medline].

  21. Yasukawa K, Sato-Matsumura KC, McMillan J, Tsuchiya K, Shimizu H. Exclusion of COL7A1 mutation in Kindler syndrome. J Am Acad Dermatol. Mar 2002;46(3):447-50. [Medline].

 
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Images show the progression of lesions. A and B: At birth, acral blisters and erosions are present. C and D: At age 5 years, atrophy and reticulated erythema with dyschromic patches are noted. E and F: At age 7 years, progressive poikilodermatous changes with reticulated erythema and telangiectasia occur. G and H: At age 10 and 15 years, poikiloderma with telangiectasia and depigmentation are observed. Excoriations are due to pruritus. Reprinted from Yasukawa K, Sato-Matsumura KC, McMillan J, et al: Exclusion of COL7A1 mutation in Kindler syndrome. J Am Acad Dermatol 2002 Mar; 46(3): 447-50. Courtesy of the American Academy of Dermatology.
 
 
 
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