Intern Med. 2026 Jun 4. doi: 10.2169/internalmedicine.7239-26. Online ahead of print.
ABSTRACT
A 46-year-old Japanese man with nonobstructive hypertrophic cardiomyopathy harboring a heterozygous PSEN1 c.367G>A (p.Glu123Lys) variant experienced sudden cardiac arrest due to ventricular fibrillation at 56 years of age. Although PSEN1 variants are primarily associated with early onset Alzheimer's disease, emerging evidence suggests a role in cardiomyopathy that is independent of the amyloid pathology. This case demonstrates a novel cardiac manifestation of presenilin 1 dysfunction. At the time of genetic diagnosis, the patient exhibited normal cognition, suggesting that cardiovascular manifestations may precede neurodegeneration. This report suggests an expansion of the phenotypic spectrum associated with PSEN1 variants and highlights the need for further investigation of potential cardiac manifestations in PSEN1 variant carriers.
PMID:42236188 | DOI:10.2169/internalmedicine.7239-26