Hypohidrotic ectodermal dysplasia (skin fragility syndrome) is an X-linked hereditary form of epidermolysis bullosa characterized by ectodermal sloughing. Affected dogs with autosomal dominant genes are associated with homozygous lethality.
The phenotype of hairless dogs is now classified as canine ectodermal dysplasia (CED) because these dogs have missing or abnormally shaped teeth in addition to a hair coat that is sparse or absent. Natural ectodermal dysplasia is found in Mexican and Peruvian hairless dogs and Chinese Crested dogs.
In affected individuals, structures of ectodermal origin may be absent or abnormally formed, including skin, lacrimal glands and teeth.
May affected dogs develop pneumonia due to the absence of tracheal and bronchial glands which are a vital part of the mucociliary clearance mechanism, and may be fatal in some cases. This respiratory deficiency is not related to immune deficiency on the respiratory epithelium.
Skin abnormalitites manifest as hairlessness and absence of eccrine sweat glands. Congenital alopecia was first described in the dog in 1910. X-linked recessive inheritance has been confirmed in one dog breed by pedigree analysis. Dental abnormalities include dental crown malformations and malocclusions in deciduous and permanent teeth. Deciduous canine teeth are commonly persistent, resulting in crowding of the erupted permanent canine teeth in half of adult affected dogs.
Ectodermal dysplasia is caused by a mutation in the PKP1 gene, which results in a very short protein, abnormal and dysfunctional superficial epidermal desmosomes, profound keratinocyte acantholysis and superficial epidermal sloughing occurring at birth.
Affected dogs are first noticed to have an unusual pale and fragile skin when first rubbed dry after delivery. The main anomalies are skin fragility and fissuring at sites of friction and around mucosae. The coexistence of skin fragility, fissuring, hypotrichosis and abnormal hair is an unusual combination of signs unique to this disease.
Diagnosis usually requires histological analysis of biopsied skin tissue, and usually shows widening of the intercellular space with dissociation between epidermal cells in the superficial epidermal layers leading to epithelial sloughing (i.e. erosions). Acantholysis is associated with the aggregation of the keratin cytoskeleton (dyskeratosis). As dogs age, the epidermis becomes hyperplastic and hyperkeratotic while acantholysis decreases. Transmission electron microscopy is useful to demonstrate a reduced number of hypoplastic desmosomes with separation of keratin intermediate filaments from desmosomal plaques.
A differential diagnosis would include cutaneous asthenia.
Recombinant ectodysplasin A, given immediately post-natally, has been shown to improve clinical symptoms.
Less severely affected dogs have a good quality of life.
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