Carney complex

Abstract

Carney complex (CNC) is an autosomal dominantly inherited syndrome characterized by spotty skin pigmentation, cardiac and cutaneous myxoma, and endocrine overactivity. Skin pigmentation includes lentigines and blue nevi. Myxomas may occur in breast, skin and heart. Cardiac myxomas may be multiple and occur in any cardiac chamber, and are more prone to recurrence. The most common endocrine gland manifestation is an ACTH-independent Cushing's syndrome due to primary pigmented nodular adrenocortical disease (PPNAD). PPNAD may occur in isolation, with no other signs of CNC. The pituitary and thyroid glands and gonads are also involved.The PRKAR1A gene, located in 17 q22-24, encodes for the type 1A regulatory subunit of protein kinase A. Inactivating germline mutations of this gene are found in 70% of patients with CNC. PRKAR1A is a key component of the c-AMP signaling pathway that has been implicated in endocrine tumorigenesis. Many different mutations have been reported in the PRKAR1A gene. In almost all cases the sequence change was predicted to lead to a premature stop codon and the resultant mutant mRNA was subject to nonsense-mediated mRNA decay. There is no clear genotype-phenotype correlation in patients with CNC.Genetic analysis should be performed in all CNC index cases. All affected patients should be monitored for clinical signs of CNC at least once a year. Genetic diagnosis allows for the more effective preparation of appropriate and effective therapeutic strategies and genetic counseling for patients and gene carriers, and prevents unnecessary tests being given to relatives not carrying the gene.