Carney Complex Syndrome
Carney Complex Syndrome
Carney Complex Syndrome (CCS) is a rare autosomal dominant multiple neoplasia syndrome characterized by spotty skin pigmentation, endocrine overactivity, and various types of tumors. It was first described by J. Aidan Carney in 1985.
Epidemiology
- Prevalence: Approximately 1 in 1,000,000
- Age of onset: Usually before 20 years old
- No gender predilection
Genetics
CCS is primarily caused by mutations in the PRKAR1A gene, located on chromosome 17q22-24. This gene encodes the regulatory subunit type 1-alpha of protein kinase A. In about 30% of cases, the genetic cause remains unknown.
Clinical Features of Carney Complex Syndrome
Cutaneous Manifestations
- Lentigines: Multiple, small, dark brown to black macules
- Blue nevi
- Cafe-au-lait spots
- Cutaneous myxomas
Endocrine Tumors
- Primary pigmented nodular adrenocortical disease (PPNAD)
- Growth hormone-secreting pituitary adenomas
- Thyroid tumors (adenomas, carcinomas)
- Large-cell calcifying Sertoli cell tumors of the testes
- Ovarian cysts
Cardiac Manifestations
- Cardiac myxomas (can occur in any chamber)
- Arrhythmias
Other Tumors
- Psammomatous melanotic schwannomas
- Breast ductal adenomas
- Osteochondromyxomas
Diagnosis of Carney Complex Syndrome
Diagnosis is based on clinical criteria and genetic testing. The presence of two or more of the following features is suggestive of CCS:
- Spotty skin pigmentation with typical distribution
- Myxoma (cutaneous and mucosal)
- Cardiac myxoma
- Breast myxomatosis or fat-suppressed MRI findings suggestive of this diagnosis
- PPNAD or paradoxical positive response of urinary glucocorticosteroids to dexamethasone administration during Liddle's test
- Acromegaly due to GH-producing adenoma
- Large-cell calcifying Sertoli cell tumor or characteristic calcification on testicular ultrasonography
- Thyroid carcinoma or multiple, hypoechoic nodules on thyroid ultrasonography, in a young patient
- Psammomatous melanotic schwannoma
- Blue nevus, epithelioid blue nevus (multiple)
- Breast ductal adenoma (multiple)
- Osteochondromyxoma
Genetic Testing
Molecular genetic testing for PRKAR1A mutations confirms the diagnosis. In cases where no mutation is found, other genes such as PRKACB and PRKAR2B may be considered.
Management of Carney Complex Syndrome
Management of CCS is multidisciplinary and focuses on regular surveillance, early detection, and treatment of associated tumors and endocrine abnormalities.
Surveillance
- Annual echocardiogram for cardiac myxomas
- Annual thyroid ultrasound
- Annual testicular ultrasound in males
- Regular skin examinations
- Endocrine evaluations (cortisol, growth hormone, prolactin)
- MRI of the pituitary gland every 2-3 years
Treatment
- Surgical removal of cardiac myxomas
- Adrenalectomy for PPNAD
- Thyroidectomy for thyroid cancer
- Transsphenoidal surgery for pituitary tumors
- Removal of cutaneous myxomas if symptomatic
Genetic Counseling
Offer genetic counseling to affected individuals and their families. Discuss the autosomal dominant inheritance pattern and the 50% risk of transmission to offspring.
