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A New Mutation and New Diagnostic Possibilities

Joanna M. Burch, MD; Hiva Fassihi, MA, MB, BChir; Catherine A. Jones; Sarah C. Mengshol, MD; James E. Fitzpatrick, MD; John A. McGrath, MD

Arch Dermatol. 2006;142:620-624.

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.

Author Affiliations: Departments of Dermatology (Drs Burch and Fitzpatrick), Pediatrics (Dr Burch), and Pathology (Dr Mengshol), University of Colorado Health Sciences Center, Denver; and Genetic Skin Disease Group, St John's Institute of Dermatology, The Guy’s, King's College, and St Thomas' Hospitals' Medical School, London, England (Drs Fassihi and McGrath and Ms Jones).

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