Carney complex is extremely rare, with an estimated prevalence of fewer than 1 in 1,000,000 individuals worldwide. About 750 cases total have been reported, often during early childhood with the appearance of sporadic bumps. Both males and females are affected equally. Many cases are familial, though sporadic cases also occur. Because of variable expression, the disorder may be underdiagnosed.

Carney complex is most commonly caused by mutations in the PRKAR1A gene, which encodes the regulatory subunit type 1-alpha of protein kinase A (PKA). This protein plays a critical role in regulating cell growth and hormone signaling. Loss-of-function mutations in PKA lead to uncontrolled cellular growth and production of hormones, leading to tumor development and a dysregulated endocrine system. The condition is inherited in an autosomal dominant manner in about 70% of cases, though approximately 30% of cases result from spontaneous mutations in offspring (see Rareshare Guide on Genetic Inheritance). Rarely, other genetic loci may be involved. A region on the short (p) arm of chromosome 2 called 2p16 has been associated with an increased risk of Carney complex (see Rareshare Guide on Chromosomal Nomenclature), yet research is ongoing.

 Symptoms vary widely depending on the organs involved and may include:

• Skin findings: Lentigines (small brown-to-black spots) on the face, lips, eyelids, genitalia; blue nevi which are raised moles with a bluish color

• Cardiac myxomas: tumors in one or more chambers of the heart that can cause shortness of breath, syncope, embolic stroke, or sudden death

• Endocrine tumors and overactivity:

  • Primary pigmented nodular adrenocortical disease (PPNAD) → Cushing syndrome, an overproduction of cortisol hormone that can lead to weight gain, slow growth in children, bone loss, and fragile skin

  • Pituitary adenomas → Excess growth hormone (acromegaly), causing enlarged hands and feet, arthritis, and distinct facial features

  • Testicular tumors (large-cell calcifying Sertoli cell tumors) → Gynecomastia or infertility

  • Thyroid nodules or cancer

• Other tumors: Cutaneous, breast, nerve sheath (psammomatous melanotic schwannomas which are tumors that form in the Schwann cell type that protects nerves), and bone lesions

Symptoms may appear gradually and recur throughout life.

Diagnosis is based on clinical criteria, family history, and genetic testing. A diagnosis can be made when two or more characteristic features are present, or when one feature is present in a patient with a confirmed PRKAR1A mutation or a first-degree relative with Carney complex.

• Genetic testing: Identification of a pathogenic PRKAR1A mutation

• Echocardiography: Regular screening for cardiac myxomas

• Hormonal testing: Cortisol, growth hormone, prolactin, thyroid hormones, and sex hormones

• Imaging studies:

  • MRI or CT of adrenal glands, pituitary, thyroid, and testes/ovaries

  • Ultrasound for thyroid and testicular lesions

• Skin examination and biopsy: For pigmented lesions or myxomas

Periodic surveillance testing: Essential due to high recurrence risk

Treatment is individualized and focuses on tumor removal, hormonal control, and long-term surveillance:

• Surgical excision of cardiac myxomas and other symptomatic or malignant tumors

• Endocrine management:

  • Adrenalectomy for PPNAD - removal of part or all of the adrenal gland located above the kidney

  • Medical or surgical treatment of pituitary adenomas

• Hormone-suppressive therapies when appropriate

• Lifelong monitoring with regular cardiac, endocrine, and imaging evaluations

Genetic counseling for affected individuals and family members

With early diagnosis and careful monitoring, individuals with Carney complex can have a near-normal life expectancy. However, prognosis depends on timely detection and treatment of the possible cardiac myxomas and endocrine tumors, which can be life-threatening if untreated. Tumor recurrence is common, necessitating lifelong follow-up. Advances in genetic testing, imaging, and surgical techniques have significantly improved outcomes and quality of life for affected individuals.

1. Medline Plus: Carney complex - Genetics

2. Cleveland Clinic: Carney complex

3. NCBI Bookshelf: Carney complex