VOHWINKEL SYNDROME, VARIANT FORM
|VOHWINKEL SYNDROME, VARIANT FORM
|Mutilating Vohwinkel palmoplantar Keratoderma without deafness, Loricrin Keratoderma; Camisa’s syndrome;
Mutilating palmoplantar keratoderma (PPK) without deafness, or Loricrin keratoderma, is a rare autosomal dominant disorder of keratinisation characterized by a diffuse transgredient honeycomb palmoplantar keratoderma with annular constrictions around digits (pseudo-ainhum), accompanied by generalized ichthyosis. The disease is caused by mutations in the gene encoding loricrin, a glycine-rich cornified envelope protein.1
Infants may be born with generalized desquamation. Presentation as a collodion baby has been reported. The ichthyosis is generally mild and may pass unnoticed. During childhood, a rugose palmoplantar keratoderma develops which gradually extends in confluence with a “honeycomb” pattern. The edges of the keratoderma are diffuse. Hyperkeratotic, cicatricial bands may develop around digits (pseudo-ainhum) sometimes resulting in autoamputation. This may cause impaired manual dexterity and impaired mobility. Less prominently, knuckle pads, star-fish and warty keratoses have been reported.2-4
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, are causative for this PPK type. 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.5, 6
The diagnosis is based on clinical examination. Histopathology may confirm the diagnosis by demonstrating the presence of retained nuclei in the thickened stratum corneum together with hypergranulosis. Immunoelectron microscopy shows the presence of aberrant loricrin in these nuclei. Molecular analysis of the loricrin gene is recommended.
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 go along with side-effects. The pseudo-ainhum may require surgical intervention in order to prevent autoamputation.
1. O'Driscoll J, Muston GC, McGrath JA, Lam HM, Ashworth J, Christiano AM. A recurrent mutation in the loricrin gene underlies the ichthyotic variant of Vohwinkel syndrome. Clin Exp Dermatol. 2002;27(3):243-246.
6. Ishida-Yamamoto A, McGrath JA, Lam H, Iizuka H, Friedman RA, Christiano AM. The molecular pathology of progressive symmetric erythrokeratoderma: a frameshift mutation in the loricrin gene and perturbations in the cornified cell envelope. Am J Hum Genet. 1997;61(3):581-589.