title: Kindler syndrome with severe mucosal involvement in a large Palestinian pedigree.
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.
  
  
  OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Dermatology Unit, Bambino Gesù Children's Hospital, IRCCS, Piazza S. Onofrio, 4; 00165, Rome, Italy.
authors.forename: May
authors.initials: M
authors.lastname: El Hachem
authors.affiliation: Dermatology Unit, Bambino Gesù Children's Hospital, IRCCS, Piazza S. Onofrio, 4; 00165, Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Diociaiuti
authors.affiliation: Laboratory of Molecular and Cell Biology, Istituto Dermopatico dell'Immacolata, IDI-IRCCS, Via Monti di Creta, 104; 00167, Rome, Italy.
authors.forename: Vittoria
authors.initials: V
authors.lastname: Proto
authors.affiliation: Dermatology Unit, Bambino Gesù Children's Hospital, IRCCS, Piazza S. Onofrio, 4; 00165, Rome, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Fortugno
authors.affiliation: Laboratory of Molecular and Cell Biology, Istituto Dermopatico dell'Immacolata, IDI-IRCCS, Via Monti di Creta, 104; 00167, Rome, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Zambruno
authors.affiliation: Laboratory of Molecular and Cell Biology, Istituto Dermopatico dell'Immacolata, IDI-IRCCS, Via Monti di Creta, 104; 00167, Rome, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Castiglia
authors.affiliation: Dermatology Section, Shifa Hospital, Shifa Street, Gaza, Gaza Strip.
authors.forename: Majdy
authors.initials: M
authors.lastname: Naim
mesh_terms: D018912:Arabs / Q000235:genetics*; D001706:Biopsy; D001768:Blister / Q000175:diagnosis / Q000235:genetics*; D004252:DNA Mutational Analysis; D004820:Epidermolysis Bullosa / Q000175:diagnosis / Q000235:genetics*; D016368:Frameshift Mutation; D006801:Humans; D008297:Male; D008875:Middle Aged; D008877:Middle East; D009092:Mucous Membrane; D010375:Pedigree; D010510:Periodontal Diseases / Q000175:diagnosis / Q000235:genetics*; D010787:Photosensitivity Disorders / Q000175:diagnosis / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D012867:Skin / Q000473:pathology*
chemical_list: D012333:RNA, Messenger
keywords: Kindler syndrome; anal and urethral strictures; blindness; dysphagia; oral involvement; symblepharon