P02 Erythrokeratodermia variabilis et progressiva due to a pathogenic variant in GJB3 gene

Abstract

Abstract Erythrokeratodermia variabilis et progressiva (EKVP) is a clinically heterogeneous group of inherited disorders characterized by the coexistence of localized or generalized hyperkeratotic plaques and transient, stationary or migratory erythematous patches. EKPV is most often transmitted in an autosomal dominant manner. Causal pathogenic variants have been detected in the GJB3, GJB4, GJA1 KDSR and KRT83 genes encoding connexins 31, 30.3, 43, 3-ketodihydrosphingosine reductase and keratin 83, respectively. Connexins are expressed in almost all tissues and pathogenic variants in the connexin genes can cause skin diseases, cardiovascular disorders, myelin-related diseases, craniofacial disorders and hearing loss. We present a 2-year-old girl who was referred to our centre with well-demarcated hyperkeratotic plaques symmetrically distributed with a predilection for the distal extremities and buttocks as well as erythematous plaques on her cheeks. The hyperkeratotic plaques were hyperpigmented, exhibited a geographic morphology and had prominent hypertrichosis. Her trunk and upper extremities were spared and her hair, teeth and nails were normal. There was family history of mild psoriasis in her mother and mild eczema in her father. Next generation sequencing confirmed she was heterozygous for the GJB3 c.625C>T p.(Leu209Phe) pathogenic variant which is associated with erythrokeratodermia variabilis et progressiva-1 (MIM 133200) and autosomal dominant deafness-2B (MIM 612644). Erythrokeratodermia variabilis is largely a skin-limited condition however GJB3 pathogenic variants can cause haring loss and neuropathy due to its expression in peripheral nerves and the cochlea. Our patient’s hearing and development have been normal to date and will be monitored.