Carney ComplexEdit

Carney complex (CNC) is a rare hereditary syndrome that blends cardiovascular, cutaneous, and endocrine manifestations. It is characterized most notably by myxomas of the heart and other tissues, spotty skin pigmentation such as lentigines, and a range of endocrine tumors. Described in the medical literature by J. A. Carney and colleagues, CNC is now understood as a single genetic condition with variable expression, so that different individuals may display different combinations and severities of features. Because cardiac myxomas can cause life-threatening obstruction or embolic events, early recognition and coordinated care are essential.

Clinicians treat CNC by integrating cardiology, dermatology, endocrinology, and genetics. Genetic testing for pathogenic variants in the PRKAR1A gene plays a central role in many cases, though a minority of patients carry mutations in other loci. The condition illustrates how a single genetic disruption in signaling pathways can produce a spectrum of tumors and pigmentary changes across multiple organ systems.

Signs and symptoms

  • Cardiac myxomas: The hallmark cardiovascular feature is the growth of myxomas in heart chambers, most commonly the left atrium. These tumors can obstruct blood flow, mimic valvular disease, or shed emboli, leading to shortness of breath, chest pain, arrhythmias, or sudden cardiac events. cardiac myxoma.

  • Cutaneous and mucosal lesions: Patients often develop spotty skin pigmentation, including lentigines, and may have cutaneous or mucosal myxomas. These pigmentary changes tend to appear in childhood or adulthood and can help prompt surveillance for other CNC features. Lentigines.

  • Endocrine tumors and overactivity: CNC predisposes to several endocrine neoplasms, including primary pigmented adrenocortical disease, which can cause Cushing syndrome, and pituitary adenomas, which may affect growth or metabolic regulation. Testicular tumors, particularly Sertoli cell tumors, can occur in males. Some patients may also develop nodular thyroid disease. primary pigmented adrenocortical disease, pituitary adenoma, Sertoli cell tumor.

  • Other features: Various gonadal and neural crest-derived lesions may appear, and pigmentary or mucocutaneous lesions can provide clues to diagnosis in families with CNC. The full spectrum is broad, reflecting the underlying disruption of cellular signaling pathways.

Genetics and pathophysiology

  • Inheritance and pattern: CNC is typically autosomal dominant, meaning a single mutated copy of the responsible gene can be sufficient to confer risk in a family. Autosomal dominant inheritance.

  • Genetic basis: Pathogenic variants in the PRKAR1A gene on chromosome 17q22-24 account for a substantial portion of CNC cases, through disruption of the cyclic AMP–dependent protein kinase A (PKA) signaling pathway. Loss of PRKAR1A function leads to dysregulated cell growth and tumor development in multiple tissues. PRKAR1A.

  • Other genetic contributors: While PRKAR1A mutations are common, a minority of CNC patients do not carry identifiable pathogenic variants in PRKAR1A, and additional genetic loci have been described or proposed. This ongoing research helps explain phenotypic variability and guides genetic counseling. cAMP signaling (as a broader category) can provide context for how these mutations alter cellular behavior.

Diagnosis

  • Clinical criteria: Diagnosis rests on recognizing a combination of major CNC features, particularly cardiac myxomas, skin or mucosal myxomas and pigmentation, and endocrine tumors. The presence of two or more major features raises suspicion for CNC and prompts genetic testing and family screening. myxoma.

  • Genetic testing: Testing for pathogenic variants in PRKAR1A supports the diagnosis and informs family risk assessments. A negative result does not entirely exclude CNC, given the existence of non-PRKAR1A cases and potential undiscovered genetic contributors. PRKAR1A.

  • Screening and surveillance: Once CNC is identified, systematic surveillance for cardiac tumors (regular imaging, often echocardiography), skin and endocrine lesions, and reproductive health is recommended. This approach aims to detect tumors early before they cause symptoms.

Management and prognosis

  • Cardiac tumors: Surgical excision of cardiac myxomas is a central life-saving intervention. Because CNC-associated myxomas can recur, long-term follow-up with periodic imaging is standard of care. cardiac myxoma.

  • Endocrine management: Hormonal excess or imbalance from endocrine tumors requires tailored therapy, such as management of Cushing syndrome from PPAD or treatment of pituitary adenomas and Sertoli cell tumors as indicated. primary pigmented adrenocortical disease, pituitary adenoma, Sertoli cell tumor.

  • Dermatologic care and surveillance: Cutaneous lesions are monitored for cosmetic impact and potential biopsy when clinically indicated. While not life-threatening, skin manifestations aid diagnosis and family screening. Lentigines.

  • Genetic counseling: Because CNC follows an autosomal dominant pattern, relatives may carry risk. Counseling covers recurrence risk, testing options, and implications for family planning. Autosomal dominant inheritance.

  • Prognosis: With improved surveillance and timely treatment of cardiac and endocrine tumors, survival has improved. Recurrence of cardiac myxomas remains a concern, underscoring the need for lifelong monitoring. The overall prognosis varies with tumor burden, age at diagnosis, and access to multidisciplinary care.

History

  • The condition is named after J. A. Carney and colleagues who first described the syndrome in the medical literature, recognizing a recurring pattern of myxomas, pigmentary changes, and endocrine tumors that clustered in families. The evolving understanding of CNC has integrated molecular genetics with clinical practice, enabling earlier detection and more targeted management. See also Carney complex for the broader historical narrative and related discoveries.

See also