Erythrokeratodermia variabilis et progressiva (EKVP) is a skin disorder that is present at birth or becomes apparent in infancy. Although its signs and symptoms vary, the condition is characterized by two major features. The first is hyperkeratosis, which is rough, thickened skin. These patches are usually reddish-brown and can either affect many parts of the body or occur in only a small area. They tend to be fixed, meaning they rarely spread or go away. However, the patches can vary in size and shape, and in some affected people they get larger over time. The areas of hyperkeratosis are generally symmetric, which means they occur in the same places on the right and left sides of the body.

EKVP can be caused by mutations in several genes, including GJB3, GJB4, and GJA1. These three genes provide instructions for making proteins called connexins 31, 30.3, and 43, respectively. These proteins are part of the connexin family, a group of proteins that form channels called gap junctions on the surface of cells. Gap junctions open and close to regulate the flow of nutrients, charged atoms (ions), and other signaling molecules from one cell to another. They are essential for direct communication between neighboring cells. Gap junctions formed with connexins 31, 30.3, and 43 are found in several tissues, including the outermost layer of skin (the epidermis).

EKVP is a rare disorder; its prevalence is unknown. More than 200 cases have been reported in the medical literature.

EKVP is most often inherited in an autosomal dominant pattern, which means one copy of an altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person inherits the mutation from one affected parent. Other cases result from new gene mutations and occur in people with no history of the disorder in their family. Very rarely, the mutation is found in some of the body's cells but not others. In these individuals, the condition is described as mosaic EKVP or inflammatory linear verrucous epidermal nevus (ILVEN). In mosaic EKVP, the characteristic skin abnormalities affect a small region of the body and usually occur on just one side. They may follow a pattern on the skin known as the lines of Blaschko.

Published Date: October 01, 2018
Published By: National Institutes of Health