Kindler syndrome with severe mucosal involvement in a large Palestinian pedigree

Eur J Dermatol. 2015 Jan-Feb;25(1):14-9. doi: 10.1684/ejd.2014.2457.

Abstract

Background: Kindler syndrome (KS) is a rare autosomal recessive disease of skin fragility, photosensitivity and progressive poikiloderma. Mucous membranes may also be involved. KS is caused by mutations in the FERMT1 gene encoding kindlin-1.

Objectives: We report the clinical and molecular features of the largest kindred with KS to date, comprising 18 affected family members (age range: 12-63 years) from the Gaza Strip.

Materials and methods: All the affected family members were clinically examined. In addition a skin biopsy for immunofluorescence testing was obtained from the index case. Molecular analysis of the FERMT1 gene was performed on genomic DNA extracted from peripheral blood of 5 patients.

Results: All patients presented skin and eye photosensitivity, cutaneous atrophy, dyschromia and poikiloderma, oral cavity involvement, dysphagia and constipation with anal fissures. In addition, nail dystrophy and digit webbing were observed in most of them. Ocular manifestations detected in all patients comprised ectropion and keratoconjunctivitis, with early development of symblepharon in 17 out of 18 cases and blindness in one. Of note, 17 out of 18 affected family members also suffered from urethral strictures since childhood. Diagnosis was supported by immunofluorescence findings and definitely confirmed by FERMT1 sequencing which identified the homozygous frame-shift mutation c.137_140delTAGT.

Conclusions: The high rate of mucosal involvement, its early onset and progressive course are noticeable features of our kindred. Also noteworthy is the lack of muco-cutaneous malignancies, despite the sunny habitat.

Keywords: Kindler syndrome; anal and urethral strictures; blindness; dysphagia; oral involvement; symblepharon.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arabs / genetics*
  • Biopsy
  • Blister / diagnosis
  • Blister / genetics*
  • DNA Mutational Analysis
  • Epidermolysis Bullosa / diagnosis
  • Epidermolysis Bullosa / genetics*
  • Frameshift Mutation*
  • Humans
  • Male
  • Middle Aged
  • Middle East
  • Mucous Membrane
  • Pedigree
  • Periodontal Diseases / diagnosis
  • Periodontal Diseases / genetics*
  • Photosensitivity Disorders / diagnosis
  • Photosensitivity Disorders / genetics*
  • RNA, Messenger / genetics*
  • Skin / pathology*

Substances

  • RNA, Messenger

Supplementary concepts

  • Poikiloderma of Kindler