Clinical and Genetic Findings in Patients With Palmoplantar Keratoderma

Area of Science:

• Dermatology
• Clinical Genetics

Background:

• Palmoplantar keratoderma (PPK) presents diagnostic challenges due to its heterogeneity.
• Limited data exists on the utility of systematic genetic testing in well-characterized PPK cohorts.

Purpose of the Study:

• To elucidate the clinical and genetic spectrum of palmoplantar keratoderma.
• To assess the diagnostic yield of genetic testing in a prospective PPK cohort.

Main Methods:

• Prospective cohort study of 142 patients with PPK (2016-2022).
• Clinical phenotyping and genetic analysis via whole-exome/genome sequencing or Sanger sequencing.
• Descriptive analysis of clinical characteristics, variant distribution, and genotype-phenotype correlations.

Main Results:

• A genetic diagnosis was achieved in 83% of 76 families, identifying 27 pathogenic variants in 13 genes.
• AAGAB variants were strongly associated with punctate PPK, demonstrating genotype-phenotype correlation.
• Variants in DSP were identified, highlighting a potential link to cardiomyopathy risk.

Conclusions:

• Genetic testing is valuable for accurate diagnosis and subtyping of palmoplantar keratoderma.
• This study establishes a well-characterized cohort for future palmoplantar keratoderma research.
• Understanding the genetic basis of PPK improves diagnostic accuracy and clinical management.