Vohwinkel Syndrome

A number sign (#) is used with this entry because of evidence that Vohwinkel syndrome (VOWNKL) is caused by heterozygous mutation in the gene encoding connexin-26 (GJB2; 121011) on chromosome 13q12.

Keratitis-ichthyosis-deafness syndrome (148210) is also caused by mutation in GJB2; another allelic disorder is palmoplantar keratoderma with deafness (148350).

A variant form of Vohwinkel syndrome, mutilating keratoderma with ichthyosis (604117), is caused by mutation in the gene for loricrin (LOR; 152445) on chromosome 1q21. A form of mutilating palmoplantar keratoderma with periorificial keratotic plaques (Olmsted syndrome; 614594) is caused by mutation in the TRPV3 gene (607066) on chromosome 17p13.2.

Clinical Features

Nockemann (1961) presented 4 generations of a family in which 4 members had hyperkeratosis, constrictions on the fingers and toes (pseudoainhum), and congenital deafness. The proband, a 20-year-old man, developed hyperkeratosis of the palms and soles beginning about 2 years of age, followed by involvement of his knees and elbows. Rubbing produced thickenings elsewhere. A few years later there developed ring-shaped furrows of the skin in the region of the middle of the 5 fingers, followed by involvement of the toes. The proband had congenital deafness. The author presented 3 other family members in 4 generations with similar findings. They were all deaf and dumb. Drummond (1939) presented the case of a 19-year-old deaf-mute girl with constricting bands around three fingers of each hand. The bands were a quarter inch wide, completely encircling each finger. Marked hyperkeratosis of the palms was also present, together with epidermal thickening over the knuckles and knees.

Gibbs and Frank (1966) described affected father and daughter, but were likely mistaken in calling it a variant of mal de Meleda, a recessive disorder. The presence of digital constrictions and the absence of leukonychia appear to distinguish this disorder from that listed under knuckle pads, leukonychia, and sensorineural deafness (149200). The hyperkeratosis and deafness reported by Morris et al. (1969) is probably a distinct entity, as they suggested. Their patient was an isolated case. Aksu and Mietens (1980) published particularly useful clinical photographs in color, together with a 3-generation pedigree. The lesions on the knees and extensor surfaces of the hands and feet resembled xanthomata superficially. The disorder was first reported by Vohwinkel (1929) in a 24-year-old man and his 14-month-old daughter. Sensi et al. (1994) referred to the condition as Vohwinkel syndrome, or mutilating keratoderma. They described a patient who had pseudoainhum of the fifth fingers, palmar and plantar hyperkeratosis, and bilateral symmetric hearing loss of cochlear origin. Cleft palate had been repaired in childhood. Sensi et al. (1994) tabulated 12 autosomal dominant and 5 autosomal recessive forms of palmoplantar keratosis.

Peris et al. (1995) reported the case of a 28-year-old woman who presented with KHM associated with congenital deaf-mutism. She had bilateral, diffuse thickening of the palms and soles, and narrow, fibrous-constricting bands at the proximal interphalangeal joints of both little fingers and the index finger of the right hand. Her parents, both deceased, were deaf but were said not to have any cutaneous disorder. However, her paternal grandfather had deaf-mutism and palmoplantar keratoderma mutilans. The hyperkeratosis of the palms and soles had been present in the proposita since the age of 5 and had progressed in severity into her teenage years. Massive, hoof-like hyperkeratosis involved the heels and the Achilles tendon area, and this developed when she was 15 years old. The nails, hair, and mucous membranes were normal. The hyperkeratosis and constricting bands improved on therapy with etretinate.

De Zwart-Storm et al. (2011) studied a 38-year-old Zimbabwean man with a 30-year history of thickened skin over the palms and soles as well as congenital sensory hearing impairment. Examination revealed palmoplantar keratoderma with hyperkeratotic papules over the knuckles and dorsum of the toes. He also had autoamputations of the fifth digits of the hands and feet, with pseudoainhum around the proximal interphalangeal joints of all remaining fingers. Similar features were reportedly present in other family members, but none were available for examination.

Mapping

Korge et al. (1997) studied 2 families, one with starfish keratoses with deafness but no ichthyosis, and the other with keratoderma and ichthyosis. They demonstrated that the classic and variant forms of Vohwinkel syndrome are clinically and ultrastructurally distinct and that the classic form does not map to the loricrin locus (152445) on chromosome 1q21.

Molecular Genetics

Maestrini et al. (1999) described a missense mutation in the GJB2 gene (D66H; 121011.0012) in affected members of a large British pedigree with Vohwinkel syndrome, and subsequently in affected individuals from 2 unrelated Spanish and Italian pedigrees. In these cases, mutilating keratoderma was associated with sensorineural deafness but not with ichthyosis.

In a 38-year-old Zimbabwean man with severe Vohwinkel syndrome, de Zwart-Storm et al. (2011) analyzed the GJB2 gene and identified heterozygosity for a missense mutation (Y65H; 121011.0041).