#124500
ICD+
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| DEAFNESS, CONGENITAL, WITH KERATOPACHYDERMIA AND CONSTRICTIONS OF FINGERS AND TOES | |||||||||||||||||||||||||||||||||||||||
| Alternative titles; symbols | |||||||||||||||||||||||||||||||||||||||
| VOHWINKEL SYNDROME MUTILATING KERATODERMA KERATODERMA HEREDITARIUM MUTILANS; KHM | |||||||||||||||||||||||||||||||||||||||
| Phenotype Gene Relationships | |||||||||||||||||||||||||||||||||||||||
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| Clinical Synopsis | |||||||||||||||||||||||||||||||||||||||
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| A number sign (#) is used with this entry because of evidence that Vohwinkel syndrome can be caused by heterozygous mutation in the gene encoding connexin-26 (GJB2; 121011) on chromosome 13q11-q12. A variant form of Vohwinkel syndrome, mutilating keratoderma with ichthyosis (604117), appears to be caused by mutation in the gene for loricrin (LOR; 152445) on chromosome 1q21. | |||||||||||||||||||||||||||||||||||||||
| 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. | |||||||||||||||||||||||||||||||||||||||
| 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, D66H, in the GJB2 gene (121011.0012) in affected members of a large British pedigree, 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. | |||||||||||||||||||||||||||||||||||||||
| See Also: | |||||||||||||||||||||||||||||||||||||||
| Camisa et al. (1988); Camisa and Rossana (1984); Hyde and Montgomery (1901) | |||||||||||||||||||||||||||||||||||||||
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