Erythrokeratodermia variabilis et progressiva

Alternate names

EKVP; Erythrokeratodermia variabilis; EKV; Erythrokeratodermia variabilis, Mendes da Costa type; Progressive symmetric erythrokeratodermia; PSEK; Erythrokeratodermia, progressive symmetric; Darier-Gottron disease; Progressiva symmetrica erythrokeratodermia; Erythrokeratoderma variabilis progressiva

Definition

Erythrokeratodermia variabilis et progressiva is a skin condition characterized by well-defined round or oval red scaly patches that may join together to form map-like patterns. Some patches are fixed, occurring most often on the outer surfaces of the arms and legs, while others are migratory - lasting for hours to days and then fading or moving to another location.

Epidemiology

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

Cause

• 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.

Gene mutations

• The GJB3, GJB4, and GJA1 gene mutations that lead to EKVP alter the structure or location of the connexins produced from these genes.
• Some GJB3 or GJB4 gene mutations lead to the production of abnormal connexins that can build up in a cell structure called the endoplasmic reticulum (ER), triggering a harmful process known as ER stress.
• Mutations in the GJA1 gene lead to the production of an abnormal connexin 43 protein that is unable to reach the cell surface to become part of gap junctions.

Inheritance

• EKVP is most often inherited in an autosomal dominant pattern.
• A few studies have shown that EKVP can also have an autosomal recessive pattern of inheritance.

Signs and symptoms

• This condition is characterized by well-defined round or oval red scaly patches that may join together to form map-like patterns.
• Some patches are fixed, occurring most often on the outer surfaces of the arms and legs, while others are migratory - lasting for hours to days and then fading or moving to another location.
• Some skin lesions are accompanied by burning or itching sensations.
• Common triggers include emotional stress, temperature changes, mechanical friction and hot or cold weather.
• Skin lesions often occur during the fist year of life, gradually progress during childhood, and then stabilize during puberty.

Diagnosis

Molecular Genetics Tests may include:

• Sequence analysis of the entire coding region
• Deletion/duplication analysis
• Targeted variant analysis
• Mutation scanning of the entire coding region

Treatment

Treatment is aimed at alleviating symptoms and may include topical retinoids or antihistamines.

NIH genetic and rare disease info

• NIH info on Erythrokeratodermia variabilis et progressiva

Erythrokeratodermia variabilis et progressiva is a rare disease.