GENETIC DISORDERS ASSOCIATED WITH CARDIAC MYXOMAS

Abstract

Cardiac myxomas are the most common primary benign tumors of the heart, accounting for approximately 50–80% of all primary cardiac neoplasms. Although most cardiac myxomas occur sporadically, approximately 7–10% are associated with inherited genetic disorders, most notably Carney complex (CNC), an autosomal dominant multiple neoplasia syndrome caused primarily by pathogenic variants in the PRKAR1A gene. Familial cardiac myxomas differ significantly from sporadic tumors in terms of age of onset, recurrence rate, multiplicity, and anatomical distribution, highlighting the importance of recognizing hereditary syndromes in affected patients. Advances in molecular genetics have revealed that dysregulation of cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) signaling represents the principal mechanism underlying hereditary cardiac myxoma development. Additional molecular pathways involving Wnt/β-catenin signaling, inflammatory cytokines, angiogenesis, and epigenetic regulation have also been implicated in tumor progression. Genetic testing has become an essential component of the diagnostic evaluation of patients with recurrent, multifocal, or early-onset cardiac myxomas, facilitating surveillance of at-risk relatives and early detection of associated endocrine and extracardiac neoplasms. This review summarizes the current understanding of the genetic disorders associated with cardiac myxomas, emphasizing the molecular basis of tumorigenesis, genotype–phenotype correlations, clinical manifestations, and implications for diagnosis, genetic counseling, and long-term surveillance.