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Carney complex (CNC) is characterized by spotty skin pigmentation, endocrine overactivity and myxomas.
ORPHA:1359Classification level: Disorder
The prevalence of CNC is unknown but it is a rare disease with around 160 index cases identified so far.
Skin pigmentation anomalies include lentigines and blue nevi. The most common endocrine gland manifestations are acromegaly, thyroid and testicular tumors, and adrenocorticotropic hormone (ACTH)-independent Cushing's syndrome due to primary pigmented nodular adrenocortical disease (PPNAD; see this term). PPNAD, a rare cause of Cushing's syndrome (see this term), is due to a primary bilateral adrenal defect that can be also observed in some patients without other CNC manifestations or a familial history of the disease. Myxomas can be observed in the heart, skin and breast. Cardiac myxomas can develop in any cardiac chamber and may be multiple.
One of the putative CNC genes located on 17q22-24, (PRKAR1A), has been found to encode the regulatory subunit (R1A) of protein kinase A. Heterozygous inactivating mutations of PRKAR1A were reported initially in 45 to 65% of CNC index cases, and may be present in about 80% of the CNC families presenting mainly with Cushing's syndrome. PRKAR1A is a key component of the cAMP signaling pathway which has been implicated in endocrine tumorigenesis and could, at least partly, function as a tumor suppressor gene.
Genetic analysis should be proposed to all CNC index cases. Patients with CNC, or with a genetic predisposition to CNC, should have regular screening for manifestations of the disease. Clinical work-up for all the manifestations of CNC should be performed at least once a year in all patients and should start in infancy.
CNC is a dominantly inherited syndrome.
Management and treatment
Cardiac myxomas require surgical removal. Treatment of the other manifestations of CNC should be discussed and may include follow-up, surgery, or medical treatment depending on the location of the tumor, its size, the existence of clinical signs of tumor mass or hormonal excess, and the suspicion of malignancy. Bilateral adrenalectomy is the most common treatment for Cushing's syndrome due to PPNAD.