Unique autosomal recessive variant of palmoplantar keratoderma associated with hearing loss not caused by known mutations

Abstract

Inherited Palmoplantar Keratodermas are rare disorders of genodermatosis that are conventionally regarded as autosomal dominant in inheritance with extensive clinical and genetic heterogeneity. This is the first report of a unique autosomal recessive Inherited Palmoplantar keratoderma -sensorineural hearing loss syndrome which has not been reported before in 3 siblings of a large consanguineous family. The patients presented unique clinical features that were different from other known Inherited Palmoplantar Keratodermas -hearing loss syndromes. Mutations in GJB2 or GJB6 and the mitochondrial A7445G mutation, known to be the major causes of diverse Inherited Palmoplantar Keratodermas -hearing loss syndromes were not detected by Sanger sequencing. Moreover, the pathogenic mutation could not be identified using whole exome sequencing. Other known Inherited Palmoplantar keratoderma syndromes were excluded based on both clinical criteria and genetic analysis.

Figure 1

Hands and feet of the patient 1. A Bilateral symmetrical diffuse planter waxy yellowish hyperkeratosis of the feet, more severe in pressure sites, less severe in the plantar arch, and associated with deep fissures and cracks all over the sole. B Asymmetrically striate and focal hyperkeratosis in both palmar surfaces without significant nail changes

Figure 2

Hands and feet of the patient 2. A - Bilateral symmetrical diffuse waxy yellowish hyperkeratosis with cracks in both plantar aspects of the soles. B - Warty papules on the knuckles of the dorsal aspect of the big toes. Note the dystrophic nail changes in the form of onychographosis (hyperkeratotic and grossly thickened nail plates) which was more severe in both big toes, but less severe in the small toes. C - Bilateral asymmetrical hyperkeratosis in the form of punctate keratoderma and focal warty keratotic papules in the palmar surface of the fingers, mainly against the interphalangeal and metacarpophalangeal joints. D - Deformed nails of both hands (non-specific nail changes)

Figure 3

Hands and feet of the patient 3. A - Soles and toes with characteristics similar to patient 2 (see fig. 2 for description). B - Hyperkeratotic projections onto normal skin at the medial aspect of big toe and first web space. C - Bilateral asymmetrical hyperkeratosis in the form of warty keratotic papules in the palmar surface of both hands and fingers