Alopecia, palmoplantar keratoderma, skin fragility and follicular hyperkeratoses due to compound heterozygous mutations in desmoplakin

Abstract

Inherited mutations in desmosome genes can present with a spectrum of skin, hair and cardiac abnormalities. Here we describe a 4-year-old Turkish boy with a cardio-cutaneous syndrome resulting from compound heterozygous nonsense mutations in desmoplakin. Early recognition of such cases by clinical awareness of the dermatological features and molecular diagnostics can improve patient management through early cardiac support, although the risk of cardiomyopathy and arrhythmias poses a major health concern.

Hereditary palmoplantar keratodermas. Part II: syndromic palmoplantar keratodermas – Diagnostic algorithm and principles of therapy

“…). Further possible findings include blisters and erosions at sites of friction or mechanical stress and psoriasiform keratoses on extensor legs and dorsal feet . Carvajal syndrome is a consequence of desmosome dysfunction that impairs heart muscle function and hair and skin physiology.…”

“…62 Palmoplantar keratoderma with left ventricular cardiomyopathy and woolly hair due to DSP mutations (Carvajal syndrome, autosomal recessive) Carvajal syndrome is an autosomal recessive condition due to DSP mutations 63 (Table 5). It manifests with PPK appearing in toddlers, usually striate on palms and focal on soles, congenital WH and arrhythmogenic left ventricular cardiomyopathy (ALVC), commonly presenting as heart failure during childhood or adolescence, localized or diffuse follicular keratosis, striated lichenoid keratoses of major flexural folds, nail dystrophies and congenital alopecia [64][65][66] (Fig. 4).…”

“…Further possible findings include blisters and erosions at sites of friction or mechanical stress and psoriasiform keratoses on extensor legs and dorsal feet. [64][65][66][67][68] Carvajal syndrome is a consequence of desmosome dysfunction that impairs heart muscle function and hair and skin physiology. Recently, DSP mutations have also been demonstrated to hinder gap junction function in both heart and skin cells.…”

Compound heterozygous mutations in desmoplakin associated with skin fragility, follicular hyperkeratosis, alopecia, and nail dystrophy

“…Desmosomes are found in the epidermis and myocardium . Mutations in desmoplakin (DSP), the most abundant component of the desmosome, may manifest with Carvajal syndrome, lethal acantholytic epidermolysis bullosa, skin fragility–wooly hair syndrome, striate palmoplantar keratoderma (PPK), and other phenotypes involving the hair, nails, and skin .…”

Skin fragility, woolly hair syndrome with a desmoplakin mutation – a case from India

“…Skin fragility syndrome can also be caused by mutations in plakophillin 1 where individuals present with widespread superficial scaling and erosions on the face, lips, palms, and soles as well as absence of eyebrows, eyelashes, and scalp hair . Hence, genetic analysis including desmoplakin, plakophillin, and plakoglobin should be considered for individuals with complex symptoms of skin fragility, woolly hair/ hypotrichosis, palmoplantar keratoderma, follicular hyperkeratosis, and nail dystrophy to confirm the clinical diagnosis …”