Vohwinkel syndrome

Vohwinkel syndrome is a rare genetic disorder characterized by skin abnormalities, including palmoplantar keratoses and pseudoainhum, with some forms also involving hearing loss.

Overview

Vohwinkel syndrome is a disorder with classic and variant forms, both of which affect the skin. In the classic form, individuals develop thick, honeycomb-like calluses on the palms of the hands and soles of the feet (palmoplantar keratoses) beginning in infancy or early childhood. Children typically exhibit distinctive starfish-shaped patches of thickened skin on the knees or the tops of the fingers and toes. Within a few years, tight bands of abnormal fibrous tissue (pseudoainhum) develop around the fingers and toes, which may cut off circulation and result in spontaneous amputation. The classic form is also associated with hearing loss.

The variant form, sometimes called loricrin keratoderma, does not involve hearing loss. Skin features include widespread dry, scaly skin (ichthyosis), particularly on the limbs, and mild reddening of the skin (erythroderma). Some infants are born with a tight, clear sheath called a collodion membrane, which is usually shed during the first few weeks of life.

Frequency

Vohwinkel syndrome is a rare disorder, with approximately 50 cases reported in medical literature.

Causes

The classic form is caused by mutations in the GJB2 gene, which provides instructions for making the protein connexin 26. This protein forms channels called gap junctions that transport nutrients, ions, and signaling molecules between cells. In the inner ear, these channels help maintain the potassium levels required to convert sound waves into electrical nerve impulses. In the skin, connexin 26 plays a role in the growth and stability of the outermost layer (the epidermis). Mutations disrupt these functions, leading to skin abnormalities and hearing impairment.

The variant form is caused by mutations in the LORICRIN gene, which provides instructions for making loricrin. Loricrin is a major component of the cornified envelope, a protein shell surrounding cells in the stratum corneum that provides a sturdy barrier for the skin. Mutations cause the altered protein to become trapped inside the cell, resulting in a thinner-than-normal envelope, which leads to ichthyosis and other skin abnormalities.

Inheritance

This condition is inherited in an autosomal dominant pattern, meaning one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, the mutation is inherited from an affected parent, though some cases result from de novo mutations in people with no family history of the disorder.