From the Guidelines
Carney complex is a rare genetic disorder that requires a multidisciplinary approach for management, including regular screening and genetic testing, to prevent morbidity and mortality associated with its various manifestations, such as cardiac myxomas and endocrine tumors, as supported by the guidelines from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors 1.
Key Features of Carney Complex
- Caused by mutations in the PRKAR1A gene, which regulates cell growth and division
- Characterized by multiple benign tumors, skin pigmentation abnormalities, and endocrine overactivity
- Patients typically present with spotty skin pigmentation (lentigines), particularly on the face, lips, and genitalia, along with myxomas (benign tumors) in the heart, skin, and breast
- Endocrine abnormalities include Cushing's syndrome from adrenal gland tumors, acromegaly from pituitary tumors, and testicular tumors in males
Management and Screening
- Regular screening, including echocardiograms to detect cardiac myxomas, which can cause sudden death if untreated
- Surgical removal of tumors is often necessary, particularly for cardiac myxomas
- Genetic testing is recommended for diagnosis confirmation and family screening, as Carney complex follows an autosomal dominant inheritance pattern, meaning children of affected individuals have a 50% chance of inheriting the condition
- Referral to genetic counseling is indicated for individuals with at least two major diagnostic criteria for Carney complex, including primary pigmented nodular adrenocortical disease, psammomatous melanotic schwannoma, and large cell calcifying Sertoli cell tumors 1
Importance of Early Detection and Treatment
- Early detection and treatment of cardiac myxomas and other manifestations of Carney complex can significantly reduce the risk of morbidity and mortality
- Regular lifelong follow-up is essential due to the risk of recurrent tumors and development of new manifestations throughout life
- A multidisciplinary approach to management, including genetic counseling, cardiology, endocrinology, and surgery, is crucial for optimal outcomes in patients with Carney complex 1
From the Research
Definition and Characteristics of Carney Complex
- Carney complex (CNC) is a rare dominantly inherited multiple neoplasia syndrome with almost full penetrance 2, 3.
- It is characterized by both endocrine and non-endocrine manifestations, including primary pigmented nodular adrenocortical disease with Cushing's syndrome, acromegaly, thyroid tumors, cardiac myxomas, cutaneous and mucosal myxomas, pigmented cutaneous lesions, psammomatous melanotic schwannoma, and osteochondromyxoma 2, 4, 5, 3.
Genetic Basis of Carney Complex
- The pathophysiology of CNC is a model of dysregulation of the cAMP/PKA signalling in human diseases 2.
- Inactivating heterozygous mutations of PRKAR1A, encoding the regulatory subunit 1α of protein kinase A, are identified in more than 70% of the index cases 2, 4, 3.
- Inactivating mutations of genes encoding phosphodiesterases are found in rare and particular forms of the complex 2, 3.
Clinical Features and Management
- Carney complex is associated with a wide range of tumors, including cardiac myxomas, which are the predominant cause of death in CNC patients 6.
- The disease is characterized by lentigines, cutaneous, mucosal, or breast myxomas, thyroid nodules, pituitary adenoma, and schwannoma 6.
- There is at present no medical specific treatment for CNC, and every confirmed or suspected CNC patient should be managed by a multi-disciplinary team according to each manifestation of the disease and offered a long-term follow-up and genetic counselling 2, 5.
Risk Factors and Prognosis
- Cardiac myxomas are common by age 30 and often recur, especially in women, but the risk drops in 10 to 20 years 6.
- The CNC-related lesions, lentigines, cutaneous, mucosal, or breast myxomas, thyroid nodules, pituitary adenoma, and schwannoma are significantly more frequent among patients with myxomas 6.