Vohwinkel Syndrome secondary to missense mutation D66H in GJB2 gene (connexin 26) can include epileptic manifestations

Abstract

Vohwinkel Syndrome (VS) is a type of diffuse hereditary palmoplantar keratodermas (DHPPK) accompanied by skeletal dimorphisms and sensorineural deafness. The most frequently reported genetic substrate in VS is a point mutation of GJB2 gene, responsible for encoding connexin 26, a gap-junction protein with a crucial role in neuronal migration in rats. We report the case of a 21-year-old male who is a second-generation member of a family with VS and developed cryptogenic focal epilepsy. Genetic study showed a nucleotide change (c.196G>C) in exon 1 of GJB2 gene, producing a missense mutation, D66H. It is plausible that a functional alteration of connexin 26, such as that resulting of the mutation of our case, can produce an alteration in cortical development with epileptogenic potential. The present case and experimental evidence that connexin 26 is related to animal epileptogenesis suggest that the phenotypic spectrum of VS could be expanded to include epileptic manifestations.

GJB2 Gene Mutations in Syndromic Skin Diseases with Sensorineural Hearing Loss.

“…Recent studies have, in fact, shown that mutant forms of Cx26 associated with skin disorders have an impact on the function of Cx43 and Cx30 [28, 45, 71, 72]. These results suggest that the precise phenotypes (deafness versus skin disease) resulting from the different dominant Cx26 mutants may depend upon both the nature of the physical interactions between different mutant and different wild-type connexins and upon their relative levels of expression in particular tissues.…”

Hereditary Palmoplantar Keratosis

“…Alopecia, hearing loss, spastic paraplegia, myopathy, ichthyosiform dermatosis, and nail abnormalities are other associated manifestations. Other reported findings are deaf-mutism, congenital alopecia universalis, pseudopelade type alopecia, acanthosis nigricans, spastic paraplegia, myopathy, nail changes, mental retardation, bullous lesions on the soles, and seizures [4]. Histological findings include hyperkeratosis, acanthosis, and a thickened granular cell layer with retained nuclei in the stratum corneum.…”

Nocardia beijingensis outside of Asia

“…In the cases reported thus far, genetic mutations have been responsible for the epidermal alterations. One mutation involves the GJB2 gene [2][3][4][5][6] and the other involves the LOR gene. 7,8 Moreover, depending on the location of the gene mutation, different types of mutations could cause various skin problems 9 with variable phenotypes (Table 1).…”

“…1 There are three types described; types I and II develop as a defect or have hamartomatous origin, and type III is a metastatic intracranial meningioma to skin. 2 Herein, we report a case with a CMH that manifested as a recurrent nodule on the scalp. A 44-year-old otherwise healthy woman presented with a 2-year history of a recurrent nodule on the scalp.…”