Erythrokeratodermia variabilis et progressiva
Erythrokeratodermia variabilis et progressiva (EKVP) is a rare skin disorder characterized by persistent patches of thickened skin and transient areas of redness.
Overview
EKVP is present at birth or becomes apparent in infancy. It is defined by two primary clinical features:
- Hyperkeratosis: Rough, thickened, reddish-brown skin patches. These are generally symmetric and fixed, meaning they rarely spread or disappear, though they may vary in size and shape.
- Erythematous areas: Patches of reddened skin that are transient. These come and go, varying in location and shape. Redness is more common in childhood and can be triggered by temperature changes, emotional stress, or trauma.
Causes
EKVP is caused by mutations in genes such as GJB3, GJB4, and GJA1. These genes provide instructions for making connexins, proteins that form gap junctions—channels on the cell surface that allow for communication and the flow of molecules between neighboring cells.
Mutations in these genes alter the structure or location of connexins. In some cases, abnormal proteins accumulate in the endoplasmic reticulum (ER), triggering ER stress, which may lead to premature cell death in the epidermis. In other cases, the abnormal connexins fail to reach the cell surface, disrupting the formation of gap junctions.
Inheritance
EKVP is most often inherited in an autosomal dominant pattern, where one copy of an altered gene is sufficient to cause the disorder. While most cases are inherited, some result from de novo (new) mutations in people with no family history. A small number of families have reported autosomal recessive inheritance, where both copies of the gene must be mutated.
In rare instances, the condition is mosaic, meaning the mutation is present in only some of the body's cells. In these cases, skin abnormalities may affect only one side of the body or follow the lines of Blaschko.