Erythrokeratodermia Variabilis-like Phenotype in Patients Carrying ABCA12 Mutations

Area of Science:

• Genetics
• Dermatology
• Rare Diseases

Background:

• Erythrokeratodermia variabilis (EKV) is a rare genodermatosis presenting with erythematous patches and hyperkeratotic plaques.
• EKV is typically autosomal dominant, with mutations in connexin genes (GJB3, GJB4, GJA1) and other genes (KDSR, KRT83, TRPM4) being known causes.
• EKV phenotype can overlap with other genodermatoses like Netherton syndrome, complicating diagnosis.

Purpose of the Study:

• To investigate the genetic basis of EKV phenotype in patients previously unclassified.
• To determine if autosomal recessive congenital ichthyosis (ARCI) can present with an EKV phenotype.
• To expand the differential diagnosis for Erythrokeratodermia variabilis.

Main Methods:

• Clinical evaluation of seven patients presenting with an EKV phenotype.
• Molecular genetic analysis to identify causative mutations.
• Classification of patients based on genetic findings.

Main Results:

• Seven patients exhibited a clear EKV phenotype.
• All seven patients were found to have biallelic mutations in the ABCA12 gene.
• These genetic findings led to the classification of these patients within the ARCI group.

Conclusions:

• Autosomal recessive congenital ichthyosis (ARCI) should be considered in the differential diagnosis of Erythrokeratodermia variabilis (EKV).
• Mutations in ABCA12 can manifest as an EKV phenotype, expanding the known clinical spectrum of ARCI.
• This study highlights the importance of comprehensive genetic testing for rare genodermatoses with overlapping phenotypes.