Carney complex

Overview

Carney complex is a rare genetic disorder characterized by the development of multiple benign tumors (myxomas), abnormal skin pigmentation, and overactivity of certain endocrine glands. It is a multisystem condition that can affect the heart, skin, endocrine organs, and nervous system. First described by Dr. J. Aidan Carney in the 1980s, the syndrome is often inherited in an autosomal dominant manner but can also occur sporadically. Early recognition is crucial due to the risk of serious complications such as cardiac myxomas or hormonal imbalances.

Causes

Carney complex is primarily caused by mutations in the PRKAR1A gene, which encodes a regulatory subunit of protein kinase A (PKA), a key enzyme in cellular signaling. Loss of function in this gene leads to uncontrolled cell growth and tumor formation. About 70% of individuals with Carney complex have identifiable PRKAR1A mutations. Inheritance is typically autosomal dominant, meaning one copy of the mutated gene from either parent is sufficient to cause the condition. In some cases, no family history is present, and the mutation arises de novo (newly in the individual).

Symptoms

Symptoms of Carney complex vary widely between individuals but often involve a combination of the following:

• Cardiac myxomas: Benign heart tumors that can lead to obstruction, arrhythmias, embolism, or sudden death

• Skin pigmentation: Lentigines (small, dark freckles), especially on the face, lips, eyelids, and genital area

• Cutaneous myxomas: Soft, flesh-colored skin tumors, often found on the eyelids, ears, or nipples

• Endocrine overactivity:

  • Primary pigmented nodular adrenocortical disease (PPNAD) causing Cushing’s syndrome

  • Thyroid nodules or tumors

  • Testicular tumors (large-cell calcifying Sertoli cell tumors)

  • Acromegaly due to pituitary adenomas

• Other tumors: Including psammomatous melanotic schwannomas (nerve sheath tumors) and breast myxomatosis

• Growth abnormalities: Some patients may show early puberty or growth hormone-related changes

Diagnosis

Diagnosis of Carney complex is based on a combination of clinical criteria, family history, and genetic testing. Diagnostic steps include:

• Clinical examination: Identification of characteristic skin lesions, myxomas, or endocrine symptoms

• Echocardiography: To detect cardiac myxomas or other heart abnormalities

• Hormonal evaluation: Tests for cortisol, ACTH, thyroid function, growth hormone, and sex hormones

• Imaging: MRI or CT scans of the adrenal glands, pituitary, thyroid, and testes

• Genetic testing: To identify mutations in the PRKAR1A gene

• Family history review: To identify autosomal dominant inheritance patterns

At least two major clinical features or one feature plus a confirmed PRKAR1A mutation are required for a definitive diagnosis.

Treatment

Treatment of Carney complex is individualized and often involves managing the tumors and hormone imbalances associated with the disorder. Key treatment approaches include:

• Surgical removal: Of cardiac myxomas, skin tumors, or endocrine tumors as needed

• Endocrine therapy: Medications or surgery to control hormone-producing tumors (e.g., adrenalectomy for Cushing’s syndrome)

• Regular surveillance: Echocardiograms, endocrine panels, and imaging studies for early detection of tumor recurrence or new growths

• Dermatologic care: Cosmetic or medical treatment of lentigines and skin myxomas if desired

• Genetic counseling: For affected individuals and their families to understand inheritance and assess risks

Prognosis

The prognosis for individuals with Carney complex varies depending on the severity and location of the tumors. With early detection and appropriate management, many patients lead normal lives. However, untreated cardiac myxomas or hormone-secreting tumors can be life-threatening. Lifelong monitoring is essential to manage tumor recurrence and hormonal complications. Regular follow-up with cardiology, endocrinology, dermatology, and oncology specialists helps improve long-term outcomes and quality of life.