Ectodermal dysplasia-skin fragility syndrome Q81.0

McGrath et al.1977

Ectodermal dysplasia skin fragility syndrome, also known as epidermolysis bullosa simplex (EBS) due to plakophilin deficiency, is a rare autosomal recessive EBS of the suprabasal type caused by a mutation in the PKB1 gene, which encodes the structural protein plakophilin. The mutation results in a loss of function of this desmosomal protein, leading to reduced structural strength of the epidermis (Doolan BJ et al. 2020). This monogenic genodermatosis is characterized by generalized puffiness with failure to thrive, superficial erosions, and rarely blistering.

The prevalence is unknown, but < 20 cases have been published to date.

Loss of function in PKB1 was present in all cases studied to date , with mutations in the consensus acceptor splice site of intron 1 (c.203-1>A or G>T) being recurrent findings (Doolan BJ et al. 2020).

The disease usually begins at birth with erythematous, fragile, easily vulnerable skin. Visible blistering is rather rare. Rather, erosions and crusting are found. Furthermore, chronic cheilitis with perioral rhagades and blepharitis. During the first months of life dystrophic nails, hypotrichosis or alopecia, absent or sparse eyelashes and eyebrows, palmoplantar keratoses, painful palmoplantar fissures become conspicuous. The expression of woolly hairs (curly hairs) is inconstant.

In the collective assembled by Doolan et al (N=18), the following symptoms were numerically listed:

• Skin fragility and onychodystrophy in all affected individuals (18/18).
• palmoplantar keratoses (16/18)
• alopecia/hypotrichosis (16/18)
• perioral fissures/cheilitis (12/15; unknown in 3 cases).

Inconstantly present were: pruritus, failure to thrive, with growth disturbances, follicular hyperkeratosis, perianal erythema and erosions (risk of constipation), hypohidrosis, difficulty walking, dysplastic dentition and recurrent bronchial infections.

The disease is often associated with significant morbidity, but life expectancy does not appear to be affected.

Desmosomes are intercellular cadherin-mediated adhesion complexes that anchor intermediate filaments to the cell membrane and are required for strong adhesion of tissues under mechanical stress. A specific component of desmosomes is plakophilin 1 (PKP1, see plakophilins below), which is mainly expressed in the stratum spinosum of the epidermis. Autosomal recessive mutations in PKP1 lead to ectodermal dysplasia skin fragility syndrome (EDSF), the first inherited Mendelian disorder of desmosomes, first described in 1997 (McGrath JA et al 1997).

An ectodermal dysplasia skin fragility syndrome with a PKP1 mutation and plakophilin deficiency has also been demonstrated in dogs (Olivry T et al 2012).

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