Ectodermal Dysplasia-Skin-Fragility Syndrome
|Disease group||Ectodermal Dysplasia|
|DISEASE NAME||ECTODERMAL DYSPLASIA-SKIN-FRAGILITY SYNDROME|
|Gene (s)||PKP1 (601975)|
Ectodermal dysplasia/skin fragility syndrome is a rare inherited disorder due to mutations in the plakophilin -1 gene (PKP1). First described in 1997 by McGrath et al., it comprises trauma-induced skin fragility, blistering, congenital ectodermal dysplasia and painful hyperkeratosis of the palms and soles.
Affected individuals may present in childhood with skin fragility and blistering, in association with fine sparse hair, reduced sweating and nail dystrophy. In addition, severe hyperkeratosis can occur on the palms and soles, withpainful fissuring of the skin.
In 1997, McGrath et a.l reported mutations in the PKP1 gene as the molecular basis of ectodermal dysplasia/skin fragility syndrome. PKP1 is located on locus 1q32 and encodes the accessory desmosomal plaque protein, plakophilin 1, which plays a key role in desmosome formation, cutaneous cell-cell adhesion and epidermal development.
Diagnosis is made by assessment of the clinical features and the identification of a mutation in the PKP1 gene. A skin biopsy may show widening of intercellular spaces between keratinocytes and ultrastructural findings of small, poorly formed desmosomes with reduced connections to the keratin filament cytoskeleton. Immunohistochemical analysis may reveal a complete absence of staining for the accessory desmosomal plaque protein plakophilin 1.
Careful management of skin fragility and blistering is fundamentally preventative and symptomatic. Treatment strategies focus on preventing the formation of new blisters, preventing and treating infections and facilitating wound healing. Hyperkeratosis treatment may include emollients, keratolytics (eg 6% salicylic acid in 70% propylene glycol), topical retinoids, topical vitamin D ointment (calcipotriol) and systemic retinoids.