Kindler syndrome (OMIM 173650) is an autosomal recessive genodermatosis characterized by
trauma-induced blistering, poikiloderma, skin
atrophy, mucosal
inflammation and varying degrees of photosensitivity. Although
Kindler syndrome is classified as a subtype of
epidermolysis bullosa, it has distinct clinicopathological and molecular abnormalities. The molecular pathology of
Kindler syndrome involves loss-of-function mutations in a newly recognized actin cytoskeleton-associated
protein, now known as fermitin family homologue 1, encoded by the gene FERMT1. This
protein mediates anchorage between the actin cytoskeleton and the extracellular matrix via focal adhesions, and thus the structural pathology differs from other forms of
epidermolysis bullosa in which there is a disruption of the
keratin intermediate filament-hemidesmosome network and the extracellular matrix. In the skin, fermitin family homologue 1 is mainly expressed in basal keratinocytes and binds to the cytoplasmic tails of beta1 and beta3
integrins as well as to fermitin family homologue 2 and
filamin-binding LIM
protein 1. It also plays a crucial role in keratinocyte migration, proliferation and adhesion. In this report, we review the clinical, cellular and molecular pathology of
Kindler syndrome and discuss the role of fermitin family homologue 1 in keratinocyte biology.