Erythrokeratodermia Variabilis-like Phenotype in Patients Carrying ABCA12 Mutations

Abstract

Erythrokeratodermia variabilis (EKV) is a rare genodermatosis characterized by well-demarcated erythematous patches and hyperkeratotic plaques. EKV is most often transmitted in an autosomal dominant manner. Until recently, only mutations in connexins such as GJB3 (connexin 31), GJB4 (connexin 30.3), and occasionally GJA1 (connexin 43) were known to cause EKV. In recent years, mutations in other genes have been described as rare causes of EKV, including the genes KDSR, KRT83, and TRPM4. Features of the EKV phenotype can also appear with other genodermatoses: for example, in Netherton syndrome, which hampers correct diagnosis. However, in autosomal recessive congenital ichthyosis (ARCI), an EKV phenotype has rarely been described. Here, we report on seven patients who clinically show a clear EKV phenotype, but in whom molecular genetic analysis revealed biallelic mutations in ABCA12, which is why the patients are classified in the ARCI group. Our study indicates that ARCI should be considered as a differential diagnosis in EKV.

Comprehensive Molecular Analysis of Disease-Related Genes as First-Tier Test for Early Diagnosis, Classification, and Management of Patients Affected by Nonsyndromic Ichthyosis

“…Although the potential of massive sequencing in the molecular diagnosis of inherited ichthyosis is well known, the diagnostic gold standard is still mainly focused on a careful clinical evaluation/classification to guide the identification of the genetic mutation [16]. However, anamnesis, physical examination, microscopy, and laboratory examination can be variable due to the genetic and phenotypic heterogeneity of different ichthyosis forms, thus making the molecular diagnosis mandatory for ichthyosis classification [24] and for differential diagnosis [25].…”