Carney complex is most commonly caused by mutations in the PRKAR1A gene on chromosome 17 (17q23-q24)
which may function as a tumor-suppressor gene. The encoded protein is a type 1A regulatory subunit of protein kinase A. Inactivating germline mutations of this gene are found in 70% of people with Carney complex.
Less commonly, the molecular pathogenesis of Carney complex is a variety of genetic changes at chromosome 2 (2p16).
Both types of Carney complex are autosomal dominant. Despite dissimilar genetics, there appears to be no phenotypic difference between PRKAR1A and chromosome 2p16 mutations.
Cardiac myxomas can be difficult to manage surgically because of recurrence within the heart, often far away from the site of the initial tumor.
In 1914 an American neurosurgeon, Harvey Cushing, reported on a patient with a pituitary tumour on whom he had operated. The post mortem findings as reported were consistent with Carney complex, though at the time this condition had yet to be described. In 2017 archived tissue from the operation in Cushing's report was subjected to DNA sequencing, revealing an Arg74His (arginine to histidine: guanine (G)-> adenosine (A) transition in the second codon position of the 74th codon in the protein) mutation in the PRKAR1A gene, confirming a diagnosis of Carney complex. Therefore, Cushing's paper appears to be the first report of this complex.
^ abStratakis, C. A.; Kirschner, L. S.; Carney, J. A. (2001). "Clinical and Molecular Features of the Carney Complex: Diagnostic Criteria and Recommendations for Patient Evaluation". Journal of Clinical Endocrinology & Metabolism. 86 (9): 4041–4046. doi:10.1210/jc.86.9.4041.
^Tsay CJ, Stratakis CA, Faucz FR, London E, Stathopoulou C, Allgauer M, Quezado M, Dagradi T, Spencer DD, Lodish M (2017) Harvey Cushing treated the first known patient with Carney complex. J Endocr Soc 1(10):1312-1321. doi: 10.1210/js.2017-00283