Ectodermal Dysplasia-Skin-Fragility Syndrome
|Disease group||Ectodermal Dysplasia|
|DISEASE NAME||ECTODERMAL DYSPLASIA-SKIN-FRAGILITY SYNDROME|
|Gene (s)||PKP1 (601975)|
Ectodermal dysplasia (ED)-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.1
Affected individuals usually present in childhood with skin fragility and blistering, in association with fine sparse hair, reduced sweating and nail dystrophy. In the first years of life (severe) palmoplantar hyperkeratosis becomes manifest (typically with painful fissuring), in addition to hyperkeratotic plaques on the limbs. Perioral cracking and chronic cheilitis frequently develop.1-3
In 1997, mutations in the PKP1 gene have been identified 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 and stabilization, cutaneous cell-cell adhesion and epidermal development.1, 4
Diagnosis is made by assessment of the clinical features and identification of a mutation in the PKP1 gene. Light microscopy may show widening of intercellular spaces between keratinocytes (particularly in the spinous layer) as well as hyperkeratosis and acanthosis. Ultrastructural findings include 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 1.1-3
A similar phenotype to ED-skin fragility syndrome has been described in association with a mutation in the gene encoding desmoplakin (DSP) that is required for function of the inner dense plaque of desmosomes. This phenotype is additionally associated with early‐onset cardiomyopathy, as DSP is also expressed in cardiac tissue in contrast to PKP1.5
Treatment strategies focus on preventing of formation of new blisters, infection prophylaxis and improving wound healing. Treatment of hyperkeratosis involves the use of emollients, keratolytics (eg. salicylic acid), topical retinoids, topical vitamin D ointment (calcipotriol) and systemic retinoids.
1. McGrath JA, McMillan JR, Shemanko CS, Runswick SK, Leigh IM, Lane EB, et al. Mutations in the plakophilin 1 gene result in ectodermal dysplasia/skin fragility syndrome. Nat Genet. 1997;17(2):240-244.
2. Sun B, Ran X, Wen P. Novel homozygous deletion of the plakophilin-1 gene in a Chinese patient with ectodermal dysplasia-skin fragility syndrome. 2020;47(7):779-781.
3. McGrath JA, Mellerio JE. Ectodermal dysplasia-skin fragility syndrome. Dermatol Clin. 2010;28(1):125-129.
4. Schmidt A, Jäger S. Plakophilins--hard work in the desmosome, recreation in the nucleus? Eur J Cell Biol. 2005;84(2-3):189-204.
5. Tanaka A, Lai-Cheong JE, Café ME, Gontijo B, Salomão PR, Pereira L, et al. Novel truncating mutations in PKP1 and DSP cause similar skin phenotypes in two Brazilian families. Br J Dermatol. 2009;160(3):692-697.