eMedicine Specialties > Dermatology > Pediatric Diseases

Kindler Syndrome

Author: Anatoli Freiman, MD, FRCPC, DABD, Consulting Staff, Division of Dermatology, Women's College Hospital, University of Toronto
Contributor Information and Disclosures

Updated: Dec 9, 2008

Introduction

Background

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.

The Medscape Genomic Medicine Resource Center may be of interest.

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.

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.

Clinical

History

  • The hallmark of Kindler syndrome is congenital blistering and photosensitivity, combined with progressive poikiloderma and diffuse cutaneous atrophy.
  • Both blistering and photosensitivity begin in infancy or early childhood and improve significantly with age. The poikiloderma appears gradually and becomes more prominent later in life. Some patients develop sclerodermoid changes of the fingers and nails.
  • Recurrent trauma-induced blister formation occurs primarily on hands and feet, which may prompt an incorrect diagnosis of epidermolysis bullosa.
  • Photosensitivity can manifest as increased susceptibility to sunburn.
  • Patients with Kindler syndrome frequently have poor dental hygiene and dental problems.

Physical

  • Diffuse poikiloderma (reticular telangiectasia, patchy hypopigmentation and hyperpigmentation, epidermal atrophy), skin fragility, and atrophic changes (cigarette paper–like wrinkled appearance of the skin) are most prominent in sun-exposed areas, most commonly on the dorsal surfaces of the hands and feet.
  • During the neonatal period and early childhood, acral blisters and bullae are seen in trauma-prone areas.
  • Dental abnormalities occur commonly in affected persons and include advanced periodontal bone loss, mild-to-severe gingivitis, dental caries, and leukokeratosis of buccal mucosa. In one study, 13 of 18 patients with the syndrome had marked periodontal disease.5
  • Less common and variable features of the syndrome include pitted or punctate palmoplantar hyperkeratosis (≤65% of individuals), webbing of fingers and toes, nail dystrophy, and, in one case report, abnormal skeletal maturation.
  • Mucosal involvement is frequent and leads to urethral, anal, and esophageal stenosis.
  • Ophthalmic abnormalities have also been described in some patients and include ectropion, keratoconjunctivitis, and conjunctival scarring.
  • Early development of actinic keratoses may occur. Squamous cell carcinoma of the lower lip and transitional cell carcinoma of the bladder have also been reported in one patient with Kindler syndrome.

Causes

Kindler syndrome has been shown to result from mutations in the KIND1 gene on band 20p12.3 (see Pathophysiology). An autosomal recessive pattern of transmission has been reported, but sporadic cases are common, with many originating in consanguineous families. Variable expressivity within families has also been documented. Mutations in the gene encoding type VII collagen (COLA7A1) have been excluded, distinguishing Kindler syndrome from dystrophic epidermolysis bullosa.

More on Kindler Syndrome

Overview: Kindler Syndrome
Differential Diagnoses & Workup: Kindler Syndrome
Treatment & Medication: Kindler Syndrome
Follow-up: Kindler Syndrome
Multimedia: Kindler Syndrome
References
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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. Haber RM, Hanna WM. Kindler syndrome. Clinical and ultrastructural findings. Arch Dermatol. Dec 1996;132(12):1487-90. [Medline].

  10. 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].

  11. 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].

  12. 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].

  13. 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].

  14. 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].

  15. 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].

  16. 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].

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

  18. 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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Further Reading

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Keywords

Kindler syndrome, Kinder-Weary syndrome, poikiloderma, hereditary acrokeratotic bullous poikiloderma of kindler and weary, MIM 173650, KIND1, kindlin-1, Kindler's syndrome, genodermatosis, acral skin blistering, congenital acral skin blistering, skin blistering, blisters, congenital blisters, skin fragility disorder, photosensitivity

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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.

Medical Editor

Franklin Flowers, MD, Chief, Division of Dermatology, Professor, Department of Medicine and Otolaryngology, 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.

Pharmacy Editor

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
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: 3M Pharmaceutical Grant/research funds Other; Graceway Pharmaceuticals Grant/research funds Other

Managing Editor

Robert A Schwartz, MD, MPH, Professor and Head of Dermatology, Professor of Medicine, Professor of Pediatrics, Professor of Pathology, Professor of 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.

CME Editor

Catherine Quirk, MD, Clinical Assistant Professor, Department of Dermatology, Brown University
Catherine 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.

 
 
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