Vohwinkel Syndrome 

Updated: Aug 13, 2019
Author: Zoltan Trizna, MD, PhD; Chief Editor: Dirk M Elston, MD 

Overview

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[1, 2] and a case of probable autosomal recessive inheritance[3] have also been described.

Connexins 26, 30, 30.3, 31, and 43 are related to cutaneous diseases associated with multiple organ involvement. Mutations in connexin 26 are linked to Vohwinkel syndrome, keratitis-ichthyosis deafness and hystrixlike ichthyosis deafness syndromes, palmoplantar keratoderma with deafness, deafness with Clouston-like phenotype, and Bart-Pumphrey syndrome.[4]

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.[5, 6, 7] 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.[8]

Etiology

Causes of the two types are as follows:

  • Ichthyosis-associated type - Insertional mutation of the loricrin gene

  • Hearing loss–associated type - Missense mutation of the connexin-26 gene[6]

Epidemiology

Frequency

The syndrome is rare, with fewer than 30 cases reported.

Race

No racial predominance is noted.

Sex

No sex predominance is reported.

Age

This syndrome usually manifests between infancy and early childhood.

Prognosis

The prognosis is good as long as medications are used. 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.[9]

Patient Education

Tailor patient education to the course and complications.

 

Presentation

History

The classic skin lesions develop at an early age. Explore the family history for abnormalities suggestive of Vohwinkel syndrome.

Physical Examination

The classic triad is as follows:

  • Diffuse palmoplantar keratoderma in a honeycombed pattern

  • Constricting bands of the digits with autoamputation (pseudoainhum)

  • Starfish-shaped hyperkeratotic plaques on the dorsum of the hands and feet, elbows, and knees (In addition, linear hyperkeratoses may be observed on the elbows and knees.)

Note the images below:

Starfish-shaped plaques. Starfish-shaped plaques.
Palmar hyperkeratosis. Palmar hyperkeratosis.
Pseudoainhum. Pseudoainhum.

Rare associated findings include scarring alopecia and nonprogressive sensorineural hearing loss at high frequencies (classic variant).

A case report of two siblings described a probable new variant of Vohwinkel syndrome with congenital hypotrichosis.[10] Cases with mental retardation[11] and an ichthyosiform presentation[12] have also been described.

Complications

Complications can include loss of digit(s) with functional impairment of the limb and hearing loss.

 

DDx

Diagnostic Considerations

The following could be considered in the differential diagnosis of palmar and plantar keratodermas:

  • Acral keratoderma
  • Palmoplantar keratoderma of Sybert
  • Olmsted syndrome
  • Palmoplantar keratoderma of Gamborg Nielsen
  • Hereditary bullous acrokeratotic poikiloderma of Weary-Kindler
  • Clouston syndrome
  • Psoriasis
  • Other causes of pseudoainhum (eg, vascular abnormalities [Raynaud disease, scleroderma, diabetes mellitus], infections [leprosy, tertiary syphilis, yaws], scar formation following ergot poisoning)
 

Workup

Imaging Studies

Obtain radiographs of the hands and feet to detect abnormalities of the underlying bones. Use craniofacial imaging studies if clinical findings justify them.

Other Tests

Audiometry is suggested to evaluate the nature and extent of hearing loss and for eventual follow-up.

Procedures

No invasive diagnostic procedures are routinely indicated.

Histologic Findings

Histologic findings are nonspecific. The constricting bands consist of fibrous connective tissue resembling scars.

 

Treatment

Medical Care

Tailor medical care to individual defects or functional impairment of the limbs or hearing.

Surgical Care

Surgical release of the constriction bands is used to preserve the digits (eg, Z-plasty, other methods for relaxing scars).

Consultations

Consultation with the following specialists may be needed:

  • Surgeon - If any deformities of the fingers or craniofacial features are present

  • Audiologist and speech therapist - If hearing loss is noted

  • Other specialists - As indicated by clinical abnormalities

  • Genetic counselor - Advisable to discuss risk of the offspring being affected by the syndrome

Diet

No dietary interventions are indicated for treatment. Oral bioavailability of retinoids is enhanced with food intake.

Activity

Activity is unrestricted.

Long-Term Monitoring

Regular follow-up by a dermatologist is recommended. Refer the patient to a surgeon if pseudoainhum develops. Further care and laboratory testing or radiography depend on the treatment selected, course, and complications. Audiologists and speech therapists may be referred on an individual basis.

 

Medication

Medication Summary

Because of the rarity of this syndrome, all treatment options are based on sporadic experience and are off-label uses. Topical treatment is usually inadequate, although keratolytics (ie, salicylates, urea) and retinoids can alleviate keratoderma. Systemic retinoids can reverse both the keratoderma and pseudoainhum; however, relapse is the rule upon discontinuation of treatment.[13] If topical retinoids are used in women with childbearing potential, inform patients about teratogenicity and apply current guidelines. Low-dose tretinoin was reported to prevent digital amputation.[14]

Retinoids

Class Summary

Retinoids decrease the cohesiveness of abnormal hyperproliferative keratinocytes and may reduce the potential for malignant degeneration. They modulate keratinocyte differentiation and have been shown to reduce the risk of skin cancer formation in patients who have undergone renal transplantation.

Isotretinoin (Accutane)

Isotretinoin is an oral agent that treats serious dermatologic conditions. It is a synthetic 13-cis isomer of naturally occurring tretinoin (trans-retinoic acid). Both agents are structurally related to vitamin A. It decreases sebaceous gland size and sebum production and may inhibit sebaceous gland differentiation and abnormal keratinization.

An FDA–mandated registry is now in place for all individuals prescribing, dispensing, or taking isotretinoin. For more information, see iPLEDGE. The registry aims to further decrease the risks of pregnancy and other unwanted and potentially dangerous adverse effects during a course of isotretinoin therapy.

Tretinoin topical (Retin-A)

Tretinoin topical inhibits microcomedo formation and eliminates the lesions present. It makes keratinocytes in sebaceous follicles less adherent and easier to remove. It is available as 0.025%, 0.05%, and 0.1% creams. It is also available as 0.01% and 0.025% gels.

Keratolytics

Class Summary

Keratolytics cause cornified epithelium to swell, soften, macerate, and then desquamate.

Salicylic acid topical (Sal-Plant, Salactic film)

By dissolving the intercellular cement substance, salicylic acid produces desquamation of the horny layer of skin, while not affecting the structure of viable epidermis (concentrations of 12-17.6%). Consider the benefit-to-risk ratio in off-label use in Vohwinkel syndrome.

Urea (Ureaphil)

Urea promotes hydration and removal of excess keratin in conditions of hyperkeratosis. Use topical preparations of 10-30%.