Mutilating Vohwinkel Palmoplantar Keratoderma without Deafness

DISEASE CARD

Disease group Keratinization disorder
DISEASE NAME MUTILATING VOHWINKEL PALMOPLANTAR KERATODERMA WITHOUT DEAFNESS
Synonymous Loricrin Keratoderma; Camisa’s syndrome; Variant Vohwinkel’s syndrom
Estimated prevalence -
OMIM 604117
Inheritance Autosomal dominant
Gene (s) Loricrin (152445)

Definition

Mutilating Vohwinkel palmoplantar keratoderma (PPK) without deafness, or Loricrin keratoderma, is a rare autosomal dominant disorder of keratinisation characterized by a diffuse transgredient honeycomb keratoderma with annular constrictions around digits (pseudo-ainhum), accompanied by a mild generalised ichthyosis. The disease is caused by mutations in the gene encoding loricrin, a glycine-rich cornified envelope protein.

Clinical Description

Infants may be born with generalized desquamation, and a collodion baby has been reported. The ichthyosis is generally mild and may pass unnoticed. During childhood, a rugose keratoderma develops which gradually extends in confluence with a “honeycomb” pattern. The edges of the keratoderma are diffuse. Cicatricial bands may develop around digits (pseudo-ainhum) sometimes resulting in autoamputation. This can result in impaired manual dexterity and impaired mobility. Less prominently, knuckle pads and warty keratoses have been reported.

Pathogenesis

The assembly of cornified cell envelopes during terminal differentiation of keratinoctyes is a complex multistage process. Sequential deposition of involucrin, loricrin, small proline rich peptides and cellular lipids and incorporation of numerous other components leads to a gradual increase in envelope thickness and rigidity. Mutations in the glycine-rich cornified envelope protein, loricrin, cause this disorder. Several different single nucleotide insertions have been identified in this gene, with all shifting the reading frame and leading to expression of an abnormal protein with a foreign, arginine-rich C-terminal peptide containing nuclear recognition signals. The mutant protein is transported to the nucleus, where it can be identified from the upper spinous layer upwards, and is thought to interfere with the regulation of cornification, resulting in hyperkeratosis.

Diagnosis

The diagnosis of Mutilating Vohwinkel PPK without deafness is based on clinical assessment of the typical honeycomb keratoderma, the presence of pseudoainhum and ichthyosis. Histopathology demonstrates the presence of retained nuclei in the thickened stratum corneum. Immunoelectron microscopy shows the presence of aberrant loricrin in these nuclei. Molecular analysis is performed on the coding region of the loricrin gene.

Treatment

Emollients and keratolytics may help keratoderma in milder cases. Regular paring of palmoplantar hyperkeratosis can be locally beneficial. Oral retinoids (acitretin 25-35mg/day) 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.