Genetic testing proves valuable in diagnosing palmoplantar keratoderma

Key takeaways:

• 83% of families had a genetic diagnosis of palmoplantar keratoderma (PPK).
• The most common genotype found in patients was AAGAB which was linked to punctate PPK.

Researchers found genetic differences in hereditary palmoplantar keratoderma subtypes, indicating that genetic testing may be a valuable tool in accurately diagnosing the disease, according to a study.

“Hereditary palmoplantar keratoderma (PPK) is a group of rare skin disorders characterized by hyperkeratinization of palms and soles,” Stine Bjørn Gram, MD, PhD, of the department of clinical genetics at Odense University Hospital in Denmark, and colleagues wrote. “The disease presents as hard and thickened skin and is often accompanied by pain, sweating and an unpleasant odor.”

Although researchers’ understanding of the genetic factors of PPK has improved, the authors pointed out that this understanding is based primarily on case studies and smaller case series. To learn more about the genetic component of this condition, Gram and colleagues conducted a larger prospective study.

The 142 included patients (median age, 52 years; 63% female) came from 76 Danish families; 76 were initially recruited probands and 66 were affected relatives with PPK. Patients encompassed all four of the PPK subtypes: punctate (55%), diffuse (34%), focal (7%) and striate (4%).

Results showed that 83% (n = 63) of families had a genetic diagnosis of PPK. Twenty-seven variants that caused disease were found among 13 genes, the most frequent of which was AAGAB (n = 69). In fact, all patients with the AAGAB gene also had punctate PPK, the most common subtype. The authors also found that all patients with punctate PPK had this genetic diagnosis.

On the other hand, the remaining 12 genotypes were only identified in patients with nonpunctate PPK. These genes, in order of most to least common, were DSG1 (n = 23), DSP (n = 7), KRT1 (n = 5), AQP5 (n = 3), LORICRIN (n = 2), KRT9 (n = 2) and single cases of KRT16, SERPINA12, CARD14, ABCA12, DST and COL7A1.

Notably, the presence of DSP variants was important due to their link to cardiomyopathy risk, the researchers wrote.

“This study provides valuable information on the clinical and genetic landscape of a large Danish cohort with PPK and shows the phenotypic and genetic diversity of the disease,” Gram and colleagues concluded. “This study illustrates the value of genetic testing indistinguishing between specific subtypes and ensuring accurate diagnosis.”