Analysis: DSP Gene Variants in PPK Linked to Cardiomyopathy Risk

Key Takeaways

• Disease-causing variants were identified in 83% of families. 
• Punctate PPK showed clear genotype-phenotype correlations; other subtypes showed complex genetic patterns.
• DSP gene variants were linked with cardiomyopathy risk.

A Danish cohort study suggests genetic testing is crucial in accurately diagnosing and subclassifying palmoplantar keratoderma (PPK), a condition marked by clinical and genetic heterogeneity.

The study was conducted between 2016 and 2022 and included data on 142 partients from 76 families (including phenotypic assessments and genetic sequencing). Researchers identified disease-causing variants in 83% of families. According to the researchers, the AAGAB gene was the most commonly implicated, with all affected individuals presenting punctate PPK.

Subtypes of PPK included punctate (55%), diffuse (34%), focal (7%), and striate (4%). While punctate PPK showed clear genetic patterns, other subtypes showed more complex associations, involving 12 different genes. Patients with variants in the DSP gene had an increased risk of cardiomyopathy, highlighting the clinical importance of genetic testing in identifying comorbid conditions.

"This study provides novel insights into the clinical and genetic spectrum of patients with palmoplantar keratoderma," the authors wrote. "It demonstrates the value of genetic testing for accurate diagnoses and to distinguish between different subtypes. The established and well-described cohort lays the foundation for future research in palmoplantar keratoderma."

Source: Gram SB, et al. JAMA Dermatology. 2024. Doi:10.1001/jamadermatol.2024.4824