Erythrokeratodermia‐Cardiomyopathy Syndrome: Expanding the <i>DSP</i> Mutational Spectrum Beyond Proline Substitutions
Erythrokeratodermia cardiomyopathy (EKC) syndrome is a rare autosomal dominant disorder characterized by generalized erythrokeratoderma and progressive dilated cardiomyopathy, caused by pathogenic variants in the SR6 domain of desmoplakin (DSP). We report two cases of EKC with novel de novo missense DSP variants at phenylalanine position 590 (F590S and F590V), expanding the mutational spectrum beyond proline substitutions. Immunostaining demonstrated disrupted desmosomal protein localization. One patient showed significant clinical improvement with ustekinumab therapy. These findings underscore the need for early cardiac monitoring and support IL-12/23p40 inhibition as a potential therapeutic strategy in EKC.
Authors
- Donald A. Glass (ORCID: https://orcid.org/0000-0003-0866-770X)
- Jing Zhou (ORCID: https://orcid.org/0000-0001-6601-4446)
- Ryland D. Mortlock (ORCID: https://orcid.org/0000-0001-9666-4394)
- Nnenna G. Agim (ORCID: https://orcid.org/0000-0002-3915-6841)
- Sepideh Hamzehlou (ORCID: https://orcid.org/0000-0003-4670-8082)
- Keith A. Choate (ORCID: https://orcid.org/0000-0003-1010-6354)
- Caroline Echeandia‐Francis
- Chao Xing (ORCID: https://orcid.org/0000-0002-1838-0502)
Institutions
- Yale University (US)
- Southwestern Medical Center (US)
- Dallas Nephrology Associates (US)
- The University of Texas Southwestern Medical Center (US)
Publication Details
- Journal
- Pediatric Dermatology
- Published
- 2025-10-14
- DOI
- https://doi.org/10.1111/pde.70048
- Primary Topic
- Ion channel regulation and function
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Institutes of Health
- National Institute of Arthritis and Musculoskeletal and Skin Diseases