Mutilating Vohwinkel Palmoplantar Keratoderma with Deafness
|Disease group||Keratinization disorder|
|DISEASE NAME||MUTILATING VOHWINKEL PALMOPLANTAR KERATODERMA WITH DEAFNESS|
|Synonymous||Keratoma hereditarum mutilans; Vohwinkel’s syndrome|
|Gene (s)||GJB2 (121011)|
Mutilating Vohwinkel palmoplantar keratoderma (PPK) with deafness, is a rare autosomal dominant disorder of keratinisation characterized by honeycomb-like keratoderma associated with stellate keratoses on the knuckles, annular constrictions around digits (pseudoainhum) and oderate sensorineural deafness. The disease is caused by mutations in the gap junction beta-2 gene encoding connexin 26.
Shiny or translucent papular hyperkeratosis on the palms and soles begins in childhood, gradually becoming confluent, with striate lesions sometimes being seen. The keratoderma is transgredient, with the edge of the keratoderma at the wrists and Achilles tendon consisting of spiky digitate hyperkeratotic projections onto normal skin, sometimes showing Koebnerisation. Warty papules on the knuckles and other extensor sites coalesce into starfish-like acral keratoses. Multiple keratoses on digits produce circumferential hyperkeratosis predisposing to the formation of cicatricial bands (pseudo-ainhum) sometimes resulting in autoamputation. The little finger and toe are most commonly affected, and this can result in impaired manual dexterity and impaired mobility. A high-tone sensorineural hearing loss is probably present from birth, but is relatively subtle and does not appear to be progressive.
Connexins are the building blocks of gap junctions, which are plasma membrane complexes facilitating and regulating the passage of small molecules between cells. Mutations in connexin genes are now known to cause several inherited human disorders, whose phenotype at least in part reflects the distribution and inferred function of the affected genes. A recurrent point mutation in the gap junction beta-2 gene encoding connexin 26, leading to the amino acid substitution D66H, has been found in a number of unrelated families with mutilating Vohwinkel PPK with deafness. This mutation occurs at a highly conserved residue in the first extracellular domain of the Cx26 molecule, and may exert its effects by interfering with assembly into connexons, docking with adjacent cells or gating properties of the gap junction, thus impairing epidermal differentiation as well as inner ear function.
The diagnosis of mutilating Vohwinkel PPK with deafness is based on clinical assessment of the typical honeycomb keratoderma, the presence of pseudoainhum, the pathognomonic stellate keratoses and moderate hearing loss. Formal auditometry may be required to document the hearing loss. Molecular analysis is performed on the gap junction beta-2 gene encoding connexin 26.
Emollients and keratolytics may help keratoderma in milder cases. Regular paring of palmoplantar hyperkeratosis can be locally beneficial. Oral retinoids (etretinate) makes the keratin more flexible and less pronounced without complete clearing, but treatment is often unsatisfactory and may be associated with side-effects. The pseudo-ainhum may require surgical intervention in order to prevent autoamputation.