Ectodermal dysplasia‐skin fragility syndrome due to a new homozygous internal deletion mutation in the PKP1 gene

Abstract

Ectodermal dysplasia-skin fragility syndrome (ED-SFS) is a rare autosomal recessive genodermatosis resulting from mutations in the PKP1 gene, encoding the desmosomal plaque protein plakophilin-1 (PKP1). Mutations in PKP1 may manifest with skin fragility and erosions, patches of scale crust on the trunk and limbs, peri-oral cracking and inflammation, hypotrichosis, palmoplantar keratoderma with painful fissuring and other somewhat variable ectodermal anomalies. Ten cases of the syndrome have been reported. We report a further case of this desmosomal genodermatosis. A 14-month old child, born to consanguineous parents, presented with a history of neonatal bullae and subsequent development of dystrophic nails, sparse eyelashes and eyebrows, woolly scalp hair, abnormal dental development and a desquamating erythematous rash at sites of trauma. A clinical diagnosis of ED-SFS was supported by skin biopsy findings of suprabasal intraepidermal clefting and a loss of immunoreactivity for PKP1. Sequencing of genomic DNA revealed a homozygous 5 base pair deletion in exon 5 of the PKP1 gene, designated c.897del5 (CAACC). This new mutation creates a frameshift, leading to a downstream premature termination codon, p.Pro299fsX61. This case highlights the clinicopathological consequences of inherited mutations in the PKP1 gene and illustrates the key role of desmosomes in skin biology.

A Plakophilin-1 Gene Mutation in an Egyptian Family with Ectodermal Dysplasia-Skin Fragility Syndrome

“…For that reason, we intend to follow the progress of our patients with this rare genodermatosis. Given the clinical similarities between the present cases and the previously described male and female patients from different races [Zheng et al, 2005;Ersoy-Evans et al, 2006;Adhe et al, 2011;Boyce et al, 2012], it seems that neither sex nor ethnic origin significantly influence the phenotypic expression of mutations in the PKP1 gene.…”

The twisting tale of woolly hair: a trait with many causes

“…The most striking feature of this syndrome is fragile skin with erosions and blisters in trauma-prone locations 28. Eleven patients have been diagnosed with this disorder,29 and while hypotrichosis was confirmed as part of the syndrome, woolly hair was diagnosed only once 30…”

Insights into Desmosome Biology from Inherited Human Skin Disease and Cardiocutaneous Syndromes

“…A variety of PKP1 mutations including missense, splice-site and nonsense are linked with phenotypes ranging from skin fragility to severe autosomal recessive ectodermal dysplasia, including perioral cracking and infl ammation, scant hair, reduced sweating and astigmatism (Boyce et al, 2012;McGrath et al, 1997; . PKP2 mutations are a major genetic cause of non-syndromic autosomal dominant ARVC (Gerull et al, 2004).…”