Carney Complex (CC)

At a glance

Carney Complex consists of spotty skin pigmentation in association with multiple neoplasias (mainly cardiac and endocrine tumors). There are two types CC and both types show similar clinical features.

Synonyms

Carney Syndrome; Myxoma Spotty Pigmentation Endocrine Overactivity Syndrome; NAME Syndrome; LAMB Syndrome (see below).

History

Initially, the term NAME Syndrome (an acronym that stands for Nevi, Atrial m yxomas, Myxoid neurofibromas, Ephelides) was proposed for this condition. Later, the term LAMB Syndrome (an acronym that stands for Lentigines, Atrial myxomas, Mucocutaneous myxomas, Blue nevi) was proposed. Both syndromes are now part of the CC. The syndrome bears the name of the American physician J. Aiden Carney, who reviewed several of these cases in 1985 and suggested a common pathogenetic link between the clinical findings.

Incidence

More than 750 cases have been reported. In the United States, cardiac myxomas occur with a frequency of 5-10:10,000, of which approximately 7% are associated with CC. The syndrome can present at any age and in either sex. No sexual or ethnic predilection has been found.

Genetic inheritance

Approximately 70% of cases are familial with autosomal dominant inheritance and very high penetrance, and sporadic occurrence secondary to de novo mutations is responsible for the remainder of cases. Carney Complex Type 1 is caused by inactivating mutations or large deletions in the PRKAR1A (Protein Kinase, c-AMP-dependent, Regulatory, Type 1, Alpha; also known as Tissue Specific Extinguisher 1) gene, which is an important regulator of the serine-threonine kinase activity catalyzed by the protein kinase A holoenzyme, and has been mapped to chromosome 17q24.2. The exact function of PRKAR1A in cell cycle regulation, growth, and/or proliferation in general and CC Syndrome in particular remains to be elucidated, but a function as a tumor suppressor gene has been discussed. The defect in Carney Complex Type 2 has been mapped to chromosome 2p16, but the exact mutations remain to be determined.

Pathophysiology

Cardiac myxomas, while histologically benign, may cause embolic phenomena, valvular obstruction, and heart failure. Myxomas are also found in the thyroid and adrenal glands, brain, breasts, and testes. Non-myxomatous tumors, such as Sertoli cell and Leydig cell tumors of the testis, pituitary adenomas, and psammomatous melanotic schwannomas, may occur. Primary pigmented nodular adrenocortical disease (PPNAD), a characteristic micronodular form of bilateral adrenal hyperplasia, causes a unique, inherited form of Cushing Syndrome. Thyroid and pituitary dysfunction have been observed. Systemic symptoms may be caused by overproduction of the proinflammatory cytokine interleukin-6 by myxoma cells.

Diagnosis

Based on the clinical findings of pigmented skin lesions associated with neoplasias (particularly myxomas). The mean age at the time of diagnosis is typically between 10 and 20 ...