Utility of genetic testing in multisite myxoma to rule out Carney complex

We read with great interest the report by Diaz and colleagues [1]. They presented a case of a 33-year-old female patient with left atrial and right ventricular myxomas. They concluded that they had a high-index of suspicion (young age, right chamber involvement and multiple sites) concerning the possible aetiology of familial myxoma in their patient, and therefore recommend follow-up with echocardiogram for the patient and all first degree relatives. This case provides the possibility of discussing the clinical and pathological features of Carney complex (CC), or familial myxoma, and the importance of identifying individuals and families with this condition for treatment and counseling. Carney complex is estimated to account for 7% of all atrial myxomas and occurs in individuals of all ages without sex preference. It is an autosomal dominant syndrome characterized by recurrent and multicentric intracardiac or extracardiac myxomas with concurrent endocrinopathies and characteristic dermatologic features. The distinctive physical stigmata of CC are present in more than 95% of affected individuals; the most typical lesion is spotty cutaneous hyperpigmentation most commonly around lips and conjunctiva and inner or outer canthi as well as vaginal and penile mucosal surfaces. Extracardiac myxomas (breast, testis, adrenal gland, thyroid gland and brain) and non-myxomatous tumors (pituitary adenoma, breast fibroadenoma and schwannoma) may be associated with non-neoplastic endocrine dysfunction, most commonly Cushing syndrome [2]. A definite diagnosis is given when two or more of the following manifestations are present: spotty skin pigmentation with typical distribution, myxoma (cutaneous and mucosal), cardiac myxoma, breast myxomatosis, breast ductal adenoma, primary pigmented nodular adrenocortical disease, acromegaly, large-cell calcifying Sertoli cell tumor, thyroid carcinoma or multiple, hypoechoic nodules on thyroid ultrasound in a child younger than age 18 years, psammomatous melanotic schwannomas, blue nevus, epithelioid blue nevus or osteochondromyxoma. We have a few questions for the authors regarding their management. First, did the patient have any of the above mentioned manifestations? If this is the case, then the diagnosis is highly suspected, therefore molecular genetic testing of PRKAR1A must be carried out to confirm the diagnosis. PRKAR1A is the only gene currently known to be associated with CC. If the mutation is present in their patient, then additional genetic screening must be conducted to identify family members at risk for the disease. In a proband diagnosed with CC, the following evaluations are recommended [2]: imaging or biochemical screening for endocrine tumors for diagnostic purposes only, thyroid ultrasonography in pediatric and young adults, testicular ultrasonography at the initial evaluation in males and abdominal ultrasonography during the first evaluation in females. We completely concur with the statement that recurrence is more common in familial variant (40% of patients with familial myxoma [3] experience recurrence of the myxoma) and that echocardiogram follow-up must be recommended. Nonetheless, we should point out the importance of repeat echocardiography twice a year after surgery during the first four years, then on a yearly basis [4]; with close follow-up relapses can be detected early and adequately treated.