Background
In 1929, Vohwinkel first described this syndrome in a 24-year-old woman who, since age 2 years, had a diffuse honeycombed palmar and plantar keratosis, in addition to distal interphalangeal creases. The constrictions ultimately led to autoamputation. The daughter of this patient experienced similar clinical lesions.
Pseudoainhum is the autoamputation of any digit secondary to keratodermas and other causes. In contrast, ainhum is the posttraumatic or postinfectious development of constricting bands of the digits resulting in autoamputation. Several categories can be distinguished, as follows:
- Ainhum (dactylolysis spontanea): Ainhum is spontaneous autoamputation of the fifth toe, predominantly affecting blacks in tropical climates. This form most likely is posttraumatic or postinfectious in nature and is uncommon in the United States.
- Congenital annular constricting bands
- Autoamputation of traumatic origin, including self-mutilation and mechanical factors, frostbite, and burns
Pathophysiology
Vohwinkel syndrome belongs to the group of palmoplantar keratodermas. It is considered to have an autosomal dominant inheritance, although sporadic cases have also been described.[1, 2]
Two mutations of the epidermal differentiation complex have been identified in Vohwinkel syndrome.
One is a missense mutation of the GJB2 gene coding connexin-26, a gap junction protein.[3, 4, 5] This mutation on chromosome 13 is associated with the classic (hearing loss–associated) Vohwinkel syndrome. Connexins are building blocks of gap junctions that are plasma membrane complexes facilitating and regulating the passage of small molecules between cells. Several other rare mutations have also been described.
Another mutation is an insertional mutation of the loricrin gene on the epidermal differentiation complex on 1q21. This protein plays a major function in the formation of the cornified cell envelope. Sequential deposition of altered loricrin during terminal differentiation of keratinocytes and other components causes an increase in envelope thickness and rigidity. A phenotype associated with ichthyosis and not deafness is observed.
An ichthyotic variant has been described with a 730insG mutation.[6]
Epidemiology
Frequency
International
The syndrome is rare, with fewer than 30 cases reported.
Mortality/Morbidity
Patients with this syndrome may have a normal life span, persistent keratoderma, potential loss of digits, and hearing loss in the classic variant. Prenatal diagnosis by DNA analysis is possible if the gene defect is known.[7]
Race
No racial predominance is noted.
Sex
No sex predominance is reported.
Age
This syndrome usually manifests between infancy and early childhood.
Lucker GP, Van de Kerkhof PC, Steijlen PM. The hereditary palmoplantar keratoses: an updated review and classification. Br J Dermatol. Jul 1994;131(1):1-14. [Medline].
ul Bari A. Keratoderma hereditarium mutilans (Vohwinkel syndrome) in three siblings. Dermatol Online J. Dec 10 2006;12(7):10. [Medline].
Bondeson ML, Nyström AM, Gunnarsson U, Vahlquist A. Connexin 26 (GJB2) mutations in two Swedish patients with atypical Vohwinkel (mutilating keratoderma plus deafness) and KID syndrome both extensively treated with acitretin. Acta Derm Venereol. 2006;86(6):503-8. [Medline].
Kelsell DP, Wilgoss AL, Richard G, Stevens HP, Munro CS, Leigh IM. Connexin mutations associated with palmoplantar keratoderma and profound deafness in a single family. Eur J Hum Genet. Jun 2000;8(6):469-72. [Medline].
Solis RR, Diven DG, Trizna Z. Vohwinkel's syndrome in three generations. J Am Acad Dermatol. Feb 2001;44(2 Suppl):376-8. [Medline].
Drera B, Tadini G, Balbo F, Marchese L, Barlati S, Colombi M. De novo occurrence of the 730insG recurrent mutation in an Italian family with the ichthyotic variant of Vohwinkel syndrome, loricrin keratoderma. Clin Genet. Jan 2008;73(1):85-8. [Medline].
White TW. Functional analysis of human Cx26 mutations associated with deafness. Brain Res Brain Res Rev. Apr 2000;32(1):181-3. [Medline].
Seirafi H, Khezri S, Morowati S, Kamyabhesari K, Mirzaeipour M, Khezri F. A new variant of Vohwinkel syndrome: a case report. Dermatol Online J. Mar 15 2011;17(3):3. [Medline].
Camisa C, Rossana C. Variant of keratoderma hereditaria mutilans (Vohwinkel's syndrome). Treatment with orally administered isotretinoin. Arch Dermatol. Oct 1984;120(10):1323-8. [Medline].
Spitz JL. Genodermatoses: A Clinical Guide to Genetic Skin Disorders. 2nd ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2004.
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