Case Report
Ectodermal dysplasia–skin fragility syndrome resulting from a new homozygous mutation, 888delC, in the desmosomal protein plakophilin 1

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We report an unusual case of an inherited disorder of the desmosomal protein plakophilin 1, resulting in ectodermal dysplasia–skin fragility syndrome. The affected 6-year-old boy had red skin at birth and subsequently developed skin fragility, progressive plantar keratoderma, nail dystrophy, and alopecia. Skin biopsy revealed widening of intercellular spaces in the epidermis and a reduced number of small, poorly formed desmosomes. Mutation analysis of the plakophilin 1 gene PKP1 revealed a homozygous deletion of C at nucleotide 888 within exon 5. This mutation differs from the PKP1 gene pathology reported in 8 previously published individuals with this rare genodermatosis. However, all cases show similar clinical features, highlighting the importance of functional plakophilin 1 in maintaining desmosomal adhesion in skin, as well as the role of this protein in aspects of ectodermal development.

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Case report

A 6-year-old-boy had peeling and fragility of his skin since birth. His mother stated that he was born with generalized erythema and erosions, and that minor trauma resulted in skin peeling. His parents were first cousins and had a similarly affected child who died at 5 months of age.

As a neonate this patient also had diarrhea, and skin biopsy at that time showed spongiosis and loss of keratinocyte adhesion, consistent with a diagnosis of acrodermatitis enteropathica. Treatment with oral zinc

Discussion

In 1997, McGrath et al1 described the first case of a human genetic disease resulting from inherited mutations in a structural component of desmosomes. The clinical features included skin erosions and peeling with histologic evidence of keratinocyte separation, clinicopathological findings that were consistent fully with desmosomal pathology. However, there also were early changes in hair and nails, suggesting that plakophilin 1 had an additional role in the development of certain ectodermal

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Cited by (34)

  • Ectodermal dysplasias: A clinical and molecular review

    2013, Actas Dermo-Sifiliograficas
    Citation Excerpt :

    It is caused by mutation in the plakophilin gene (PKP1), located on chromosome 1 (locus 1q32).157 PKP1 is a structural component of desmosomes and is expressed in the stratified squamous epithelium, the myocardium, the meninges, and part of the lymph nodes.158 Like other types of epidermolysis bullosa, the condition is characterized by substantial trauma-induced skin fragility, generalized erythema, alopecia, nail dystrophy, and focal keratoderma with painful fissures (Fig. 17).

  • Disorders of epidermal maturation and keratinization

    2009, Weedon's Skin Pathology: Third Edition
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Funding sources: Laboratory research funding from the Dystrophic Epidermolysis Bullosa Research Association (DebRA, UK) and the National Foundation for Ectodermal Dysplasias is gratefully acknowledged.

Conflicts of interest: None identified.

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