Kindler syndrome: a new mutation and new diagnostic possibilities.

BACKGROUND Kindler syndrome (KS) is a rare genetic disorder that is characterized by blistering in infancy, followed by the onset of poikiloderma and photosensitivity in childhood. The recently elucidated molecular pathogenesis involves mutations in KIND1, a gene encoding the protein kindlin-1, which is involved in the attachment of the actin cytoskeleton to the extracellular matrix in basal keratinocytes. OBSERVATIONS We describe a child with the neonatal diagnosis of epidermolysis bullosa simplex who developed poikiloderma and skin fragility at 6 years of age. His skin showed diminished staining with anti-kindlin-1 antibody, and genetic analysis revealed that he was a compound heterozygote with a previously unreported mutation in KIND1. Ultrastructural clues to the diagnosis of KS were present in a biopsy specimen that was obtained when the patient was 10 months old, before he developed poikiloderma and photosensitivity. CONCLUSIONS In this case, a combination of a known mutation (R271X) and a newly described mutation (1755delT) in the KIND1 gene produced loss of function in kindlin-1, leading to the clinical features of KS. Ultrastructural findings characteristic of KS were evident years before the onset of poikiloderma and sun sensitivity. In infancy, electron microscopy can enable early, accurate diagnosis of KS.

[1]  J. McGrath,et al.  Recurrent mutations in kindlin-1, a novel keratinocyte focal contact protein, in the autosomal recessive skin fragility and photosensitivity disorder, Kindler syndrome. , 2004, The Journal of investigative dermatology.

[2]  H. Feiler,et al.  Loss of kindlin-1, a human homolog of the Caenorhabditis elegans actin-extracellular-matrix linker protein UNC-112, causes Kindler syndrome. , 2003, American journal of human genetics.

[3]  J. Weissenbach,et al.  Identification of mutations in a new gene encoding a FERM family protein with a pleckstrin homology domain in Kindler syndrome. , 2003, Human molecular genetics.

[4]  H. Shimizu,et al.  Exclusion of COL7A1 mutation in Kindler syndrome. , 2002, Journal of the American Academy of Dermatology.

[5]  M. Wygoda,et al.  Kindler syndrome complicated by squamous cell carcinoma of the hard palate: successful treatment with high‐dose radiation therapy and granulocyte–macrophage colony‐stimulating factor , 2001, The British journal of dermatology.

[6]  E. Erkek,et al.  Kindler syndrome: absence of definite ultrastructural feature. , 1999, Journal of the American Academy of Dermatology.

[7]  R. Burgeson,et al.  Immunohistochemical, ultrastructural, and molecular features of Kindler syndrome distinguish it from dystrophic epidermolysis bullosa. , 1997, Archives of dermatology.

[8]  W. Hanna,et al.  Kindler syndrome. Clinical and ultrastructural findings. , 1996, Archives of dermatology.

[9]  G. Pasquinelli,et al.  Kindler Syndrome: Report of a Case with Ultrastructural Study and Review of the Literature , 1996, Pediatric dermatology.

[10]  Y. Horiguchi,et al.  Kindler Syndrome: Report of Two Cases and Review of the Literature , 1989, Pediatric dermatology.

[11]  A. Hovnanian,et al.  Poikiloderma of Theresa Kindler: Report of a Case with Ultrastrectural Study, and Review of the Literature , 1989, Pediatric dermatology.

[12]  L. Goldsmith,et al.  Kindler's syndrome. , 1978, Archives of dermatology.

[13]  P. Weary,et al.  Hereditary acrokeratotic poikiloderma. , 1971, Archives of dermatology.

[14]  T. Kindler.  CONGENITAL POIKILODERMA WITH TRAUMATIC BULLA FOKMATION AND PROGRESSIVE CUTANEOUS ATROPHY. , 1954, The British journal of dermatology.