Cardiac myxomas are neoplasms that occur in at least 7 per 10,000 individuals. They are the most common primary cardiac tumor in adults.1 The typical cardiac myxoma is a sporadic, benign, nonrecurring left atrial tumor. These neoplasms are thought to arise from primitive, subendocardial, pluripotent, mesenchymal cells.2 Morbidity and mortality from cardiac myxomas is the result of embolic stroke, heart failure, and/or constitutional symptoms. Prompt surgical resection of cardiac myxomas is recommended.
A significant portion of cardiac myxomas is related to Carney complex,3 a familial autosomal dominant syndrome. Familial cardiac myxomas are associated with spotty pigmentation of the skin; endocrine dysfunction; extracardiac (most often cutaneous) myxomas; schwannomas; pituitary adenomas; thyroid tumors; testis tumors; ovarian tumors; and breast tumors. Not all patients with Carney complex develop cardiac myxomas, but affected individuals usually have at least two components of the complex, or one component as well as a significant family history.
Clinical evaluation and genetic linkage analyses4,5 of families affected by Carney complex have suggested two chromosomal loci: chromosome 2p16 and chromosome 17q24. Linkage to the chromosome 17q24 locus was initially observed in 4 families affected by Carney complex.4 Positional cloning studies have determined that familial cardiac myxomas and Carney complex, linked to chromosome 17q24, are caused by mutations in the PRKAR1α gene that encodes the R1α regulatory subunit of cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA). Haploinsufficiency of PRKAR1α in Carney complex patients predicts a tumor-suppressor function for this gene.6,7 Although some tumors of Carney complex patients with mutations of PRKAR1α show loss-of-heterozygosity (LOH) at chromosome 17q24, this is not a universal finding and is apparently not required for tumorigenesis.6,7 Thus, Carney complex is a multiple neoplasia syndrome which, like Peutz-Jeghers syndrome, is associated with dermatologic abnormalities and is caused by gene mutations that modify the activity of a protein kinase.
Carney complex is a familial multiple neoplasia syndrome characterized by cardiac myxomas in the setting of spotty skin pigmentation and endocrinopathy.8 First described in 1973 by Rees et al.,9 the disorder was initially referred to by the acronyms NAME (Nevi, Atrial myxoma, Myxoid neurofibromata, Ephelides)10 or LAMB (Lentigines, Atrial myxoma, Mucocutaneous myxoma, Blue nevi).11 Others have called this disease “Syndrome Myxoma”12 and Swiss-syndrome.13 Several detailed clinicopathologic analyses of familial and sporadic cardiac myxoma cohorts have led to the commonly used eponym Carney complex.3 Although cardiac myxomas are usually benign nonmetastatic lesions that are readily amenable to surgical resection, individuals with Carney complex account for an unusual subset of cardiac myxoma patients with an aggressive recurrent autosomal dominant tumor syndrome. Recent molecular analyses have demonstrated that the genetic etiologies of Carney complex are heterogeneous but that the major cause of Carney complex are mutations in the PRKAR1α gene encoding the R1α subunit of cAMP-dependent protein kinase A.