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Carney Complex.

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GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2019.
2003 Feb 5 [updated 2018 Aug 16].

Author information

1
Chief, Section on Endocrinology and Genetics, Scientific Director, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland
2
Office of the Clinical Director, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland

Excerpt

CLINICAL CHARACTERISTICS:

Carney complex (CNC) is characterized by skin pigmentary abnormalities, myxomas, endocrine tumors or overactivity, and schwannomas. Pale brown to black lentigines are the most common presenting feature of CNC and typically increase in number at puberty. Cardiac myxomas occur at a young age, may occur in any or all cardiac chambers, and can manifest as intracardiac obstruction of blood flow, embolic phenomenon, and/or heart failure. Other sites for myxomas include the skin, breast, oropharynx, and female genital tract. Primary pigmented nodular adrenocortical disease (PPNAD), which causes Cushing syndrome, is the most frequently observed endocrine tumor in CNC, occurring in approximately 25% of affected individuals. Large-cell calcifying Sertoli cell tumors (LCCSCTs) are observed in one third of affected males within the first decade and in most adult males. Up to 75% of individuals with CNC have multiple thyroid nodules, most of which are nonfunctioning thyroid follicular adenomas. Clinically evident acromegaly from a growth hormone (GH)-producing adenoma is evident in approximately 10% of adults. Psammomatous melanotic schwannoma (PMS), a rare tumor of the nerve sheath, occurs in an estimated 10% of affected individuals. The median age of diagnosis is 20 years.

DIAGNOSIS/TESTING:

The diagnosis of CNC is established in a proband with two or more major diagnostic criteria and/or by identification of a heterozygous germline pathogenic variant in PRKAR1A on molecular genetic testing.

MANAGEMENT:

Treatment of manifestations: Open-heart surgery for cardiac myxomas; surgical excision of cutaneous and mammary myxomas; bilateral adrenalectomy for Cushing syndrome; transsphenoidal surgery for pituitary adenoma; surgery for cancerous thyroid adenomas; orchiectomy for boys with aggressive LCCSCT and gynecomastia to avoid premature epiphyseal fusion and induction of central precocious puberty (mild gynecomastia may be treated medically); surgery to remove primary and/or metastatic PMS. Prevention of primary manifestations: Surgical removal of a cardiac myxoma prior to the development of heart dysfunction, stroke, or other embolism. Prevention of secondary complications: Medical or surgical treatment of endocrine manifestations may prevent the metabolic abnormalities from Cushing syndrome or arthropathy and complications from acromegaly. Surveillance: For prepubertal children: echocardiography annually or biannually for those with a history of excised myxoma; testicular ultrasound with close monitoring of linear growth rate and annual pubertal staging. For postpubertal children and adults: echocardiogram annually or biannually for those with a history of excised myxoma; annual testicular ultrasound; baseline thyroid ultrasound with repeat as necessary; baseline transabdominal ultrasound of the ovaries with repeat as necessary; annual urinary free cortisol levels; annual serum IGF-1 levels. Further evaluation in all age groups may include: diurnal cortisol levels, dexamethasome stimulation test, and adrenal computed tomography for primary pigmented nodular adrenocortical disease; pituitary MRI, 3-hour oral glucose tolerance test, and 90-minute thyroid releasing hormone testing for gigantism/acromegaly; MRI (brain, spine, chest, abdomen, retroperitoneum, pelvis) for psammamotous melanotic schwannoma. Evaluation of relatives at risk: When the family-specific pathogenic variant is known, molecular genetic testing to clarify the genetic status of at-risk family members so that appropriate evaluation and surveillance can enable early diagnosis of treatable manifestations.

GENETIC COUNSELING:

CNC is inherited in an autosomal dominant manner. Approximately 70% of individuals diagnosed with CNC have an affected parent; approximately 30% have a de novo pathogenic variant. Each child of an individual with CNC has a 50% chance of inheriting the pathogenic variant. Prenatal testing for pregnancies at increased risk is possible if the pathogenic variant in the family is known.

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