Dominant variants in the gap junction beta-2 (<i>GJB2</i>) gene may lead to various degrees of syndromic hearing loss (SHL) which is manifest as sensorineural hearing impairment and hyperproliferative epidermal disorders, including palmoplantar keratoderma with deafness (PPKDFN). The gene discussed is GJB2; the disease is palmoplantar keratoderma-deafness syndrome.