What is the recommended management plan for a patient under 40 with familial Carney complex, considering their genetic predisposition and potential for cardiac myxomas, endocrine tumors, and other manifestations?

Management of Familial Carney Complex in Patients Under 40

Patients under 40 with familial Carney complex require immediate echocardiographic surveillance every 6-12 months for cardiac myxomas, annual endocrine screening for primary pigmented nodular adrenocortical disease (PPNAD) and growth hormone excess, and genetic testing for PRKAR1A mutations to confirm diagnosis and guide family screening. 1, 2

Initial Diagnostic Confirmation

Establish the diagnosis systematically by assessing for:

• Spotty brown-to-black lentigines on lips, conjunctiva, canthi, and genital mucosa (present in majority of cases) 2
• Multiple blue nevi, including epithelioid blue nevus subtype 1, 2
• Cutaneous and mucosal myxomas 1, 2
• Cardiac myxomas on echocardiography 1
• Endocrine manifestations including cushingoid appearance or acromegalic features 2

Genetic referral is indicated when any one major criterion (spotty skin pigmentation, cutaneous/mucosal myxoma, or epithelioid blue nevus) is present PLUS one additional Carney complex criterion. 1, 2 PRKAR1A mutations are found in 71% of individuals meeting at least two major diagnostic criteria, making genetic testing highly informative. 2

Cardiac Surveillance Protocol

Perform baseline transthoracic echocardiography immediately, then repeat every 6-12 months indefinitely. 3, 4 This aggressive surveillance is critical because:

• Cardiac myxomas in Carney complex are multiple, recurrent, and can occur in any cardiac chamber 3, 4, 5
• Recurrence has been documented as late as 16 years after initial resection 4
• Right-sided myxomas, though less common, do occur and carry significant morbidity 5
• Myxomas can develop at young ages and cause embolic complications or sudden death 3

If cardiac myxoma is detected, refer immediately for surgical resection under cardiopulmonary bypass. 3 Post-operative echocardiographic surveillance must continue at the same 6-12 month intervals given the 7% recurrence rate specific to Carney complex-associated myxomas. 5

Endocrine Screening Algorithm

Perform annual screening for PPNAD starting at diagnosis:

• 24-hour urinary free cortisol 6
• Morning cortisol and ACTH levels 6
• Overnight 1 mg dexamethasone suppression test 6

PPNAD presents with cyclic or ACTH-independent hypercortisolism, and at least 50% of individuals with isolated PPNAD have PRKAR1A mutations and may develop other manifestations later. 2, 6

Screen annually for growth hormone excess:

• IGF-1 levels 1
• Clinical assessment for acromegalic features 2

Growth hormone-producing pituitary adenomas are a major endocrine manifestation of Carney complex. 1

Perform annual thyroid ultrasound and TSH screening given the association with thyroid tumors in Carney complex. 1, 5

Additional Surveillance Requirements

For male patients, perform annual testicular ultrasound to screen for large-cell calcifying Sertoli cell tumors, which are part of the Carney complex spectrum. 5

Assess bone lesions clinically and with imaging if symptomatic for osteochondromyxomas. 7, 1

Evaluate breast tissue in female patients for myxomatosis and multiple ductal adenomas. 7, 1

Family Screening Protocol

Screen all first-degree relatives with:

• Baseline echocardiography 3
• Clinical examination for cutaneous features 2
• Genetic testing for the familial PRKAR1A mutation if identified in the proband 8, 3

Molecular genetic testing can identify affected family members before clinical manifestations develop, allowing for early surveillance and prevention of life-threatening complications. 8, 3

Critical Pitfalls to Avoid

Do not dismiss lentigines as benign freckles—Carney complex lentigines characteristically involve mucosal surfaces (lips, conjunctiva, genital mucosa), not just skin. 2

Do not assume a single myxoma resection is curative—cardiac myxomas in Carney complex are inherently recurrent and multiple, requiring lifelong surveillance. 3, 4

Do not overlook isolated endocrine findings—even patients presenting with only PPNAD may have PRKAR1A mutations and develop cardiac myxomas later. 2

Do not limit cardiac surveillance to the left atrium—myxomas can occur in any cardiac chamber, including right ventricle and right atrium. 5

If cardiac myxomas are multiple and recurrent at a relatively young age, consider Carney complex even in the absence of other features. 4 The diagnosis may become apparent only after years of follow-up and serial evaluations. 4, 5