Vohwinkel syndrome (VS) is a rare autosomal dominant condition classified as hearing impairment (HI) in conjunction with a keratoderma of the soles and palms with additional constrictions (or pseudoainhum) sometimes resulting in autoamputation of the digit. The keratoderma in this disease manifests as popular and of honeycomb appearance, and starfish-like acral keratoses (knuckles) on the dorsal aspects of the hands and feet. The sensorineural hearing loss in VS is mild-to-moderate in degree. Clinically, this condition manifests in infants and becomes more evident in adulthood.

The treatment of this keratoderma is very difficult and tends to be symptomatic: topical keratolytics and systemic retinoids have been used to treat hyperkeratosis, but without consistent results. Reconstructive surgery with total excision of the hyperkeratotic skin followed by grafting is utilized for the treatment of pseudoainhum. The prognosis is good as long as medications are used; patients with this syndrome may have a normal life span.

Vohwinkel syndrome is caused by heterozygous mutation in the GJB2 gene encoding connexin-26 (CX26) on chromosome 13q11-q12. Connexin 26 is a member of a large family of gap junction membrane proteins. Gap junctions are intercellular channels which are permeable to ions and small molecules up to about 1 kDa in size. In the cochlea, CX26 is most likely involved in the recycling of potassium ions from hair cells back to the endolymph. This potassium recycling will presumably be impaired when CX26 gap junctions are disrupted thereby causing hearing impairment. Gap junction proteins are also prominent in the skin, but their precise function there is largely unknown. Although most mutations in GJB2 cause non-syndromic HI, some mutations cause additional skin abnormalities. Mutations in skin-expressed gap junction genes disrupt epidermal growth and differentiation.