Carney Complex

Carney complex is a rare genetic disorder characterized by increased risk of tumors growing in different parts of the body.

Many people associate “tumors” with cancer. But in Carney complex, most tumors are noncancerous, or benign. In addition, they usually do not spread to other parts of the body.

Tumors related to Carney complex may cause health problems based on:

• Size
  • Small tumors, such as adenomas (small), nodules (smaller), or lesions (smallest), may not cause any symptoms. For example, thyroid nodules usually do not require treatment, because they are too small to cause symptoms.
  • Larger tumors, including those on the heart called myxomas, may physically block blood vessels, leading to serious symptoms and sudden death.
• Whether they secrete hormones
  • Functioning (also called secretory) tumors or adenomas produce hormones and cause hormone imbalances. For example, a functioning tumor on the pituitary gland can cause high levels of growth hormone, resulting in gigantism or acromegaly (a type of overgrowth).
  • Nonfunctioning (also called nonsecretory) tumors or adenomas do not produce hormones. But they can disrupt the normal shape or size of and organ and cause problems with that organ’s functioning.

Because it is a genetic disorder, Carney complex can be inherited, meaning it may pass from parent to child through the genes. But the genetic change can also occur randomly, even if no one else in the family has the condition.

The disorder was named for the Mayo Clinic’s J. Aidan Carney, M.D., Ph.D., who first described it in 1985. There is still much for researchers to learn about this rare condition.

Who gets Carney complex?

Carney complex affects people of all ages, backgrounds, and ethnicities. People can be diagnosed at any age, and the symptoms may vary depending on a person’s age.

Although males are just as likely as females to have Carney complex, some related conditions, such as Cushing syndrome, occur more often in females.

People whose parents have Carney complex or a gene mutation that causes it are much more likely than other people to have Carney complex.

How many people have Carney complex?

Carney complex is a rare disorder. Since the condition was first described in 1985, only around 750 people worldwide have been diagnosed.¹ Because it is not well known, even to healthcare providers, Carney complex may be more common than statistics show, meaning more people may have the condition but not be diagnosed.

Carney complex can affect many different parts of the body, from the skin to the heart.¹

A key symptom of Carney complex is freckle-like skin spots, called lentigines. Although they resemble freckles, lentigines may appear at birth and do not always darken in the sun. Lentigines usually appear on the lips, eyes, and mucous membranes. Lentigines get darker during puberty but tend to fade after age 40. People with Carney complex may also have moles, called blue nevi, and café-au-lait spots (flat spots of color) on the skin.^1,2

Other symptoms of Carney complex depend on the location of tumors, their size, and how the tumors affect the function of body organs and tissues.

In Carney complex, tumors may grow in the following areas: on connective tissues, such as skin and muscle; on endocrine glands, such as adrenals or pituitary; on reproductive organs, such as testes or ovaries; and on or around nerves and bones. Select a tumor location to learn more.

Carney complex is caused by a mutation in a specific gene or genes. It can be inherited (passed from parent to child), or it can occur randomly.

Most cases of Carney complex are caused by a change or mutation in the PRKAR1A gene. Researchers think that this gene, located on chromosome 17, usually suppresses or prevents tumor growth. But the genetic mutation in Carney complex makes the gene promote or cause tumor growth.

In some cases, mutations in genes on chromosome 2—PRKACA, PRKCAB, PDE11A, or PDE8B—cause Carney complex.^1,2

Carney complex may also occur when a genetic mutation occurs randomly, meaning other family members do not have the mutated gene. Healthcare providers call these sporadic or de novo mutations.^1,2

Up to about one-third of people with Carney complex symptoms have no mutations in genes linked to the condition. For this reason, a negative genetic test result does not always mean a person does not have Carney complex—especially if another family member has it. Researchers are working to identify additional genes that may cause or contribute to Carney complex.^1,2

About Inheritance of Carney Complex

Genes are pieces of DNA that carry the instructions for “building” a body and controlling its functions. Chromosomes are packages of genes and other materials. Because chromosomes exist in pairs, people usually have two copies of a single gene—one on each chromosome in the pair. Most people have 23 pairs of chromosomes—22 numbered chromosomes and 1 sex chromosome (XX for females and XY for males).

Carney complex genes pass from one generation to the next through autosomal dominance. Autosomal means the gene is on a numbered chromosome, such as chromosome 17, instead of a sex chromosome. Dominance means that a change or mutation in just one copy of the gene causes the condition. The mutated gene “dominates” the nonmutated gene.

But not everyone who has the mutated gene will develop symptoms of Carney complex. In some cases, despite the mutated gene, the person does not develop the disease or develops only mild symptoms. This situation is called “incomplete penetrance,” which means that the mutation does not always cause clinical symptoms.

Each child of a parent who has the mutated gene has a 50% chance of having the same genetic mutation. For this reason, genetic counseling is important for people with Carney complex who plan to have a family.^1,2

To diagnose Carney complex, healthcare providers look for symptoms such as freckle-like spots on the skin and tumors in different places throughout the body. They may also run genetic and other tests to diagnose the condition.

Healthcare providers will diagnose Carney complex in a person with two or more symptoms from the following list or in a person with one of these symptoms as well as an immediate family member with Carney complex or a genetic test result that is positive for Carney complex.

Healthcare providers look for the following symptoms:¹

• Spotty skin pigmentation (dark spots) around the lips, eyelid, corners of the eye, the vagina or penis
• Multiple dark blue/black moles
• Tumors on/in/under the skin, heart, or breast
• Primary pigmented nodular adrenocortical disease or a positive dexamethasone suppression test (sometimes called a Liddle test)
• Nodules, adenomas, tumors, or carcinomas on the thyroid gland
• Acromegaly/gigantism (overgrowth of bones)
• Calcium deposits or large-cell calcifying Sertoli cell tumors in the testes
• Breast or ductal adenomas or tumors
• Tumors of nerve sheath (psammomatous melanotic schwannomas)
• Tumors on the bone, called osteochondromyxomas (rare)

Healthcare providers might also look for these other symptoms:²

• Intense freckling (without darkly pigmented spots or typical distribution)
• Café-au-lait spots or other birthmarks
• Multiple skin tags or other skin lesions or lipomas (benign fatty tumors)
• An enlarged heart (cardiomyopathy)
• A history of Cushing syndrome (high cortisol levels), acromegaly/gigantism, or sudden death in the extended family
• A “pitted” area in the skin at the base of the spine, called a pilonidal sinus
• Elevated insulin-like growth factor-1 (IGF-1) levels or elevated growth hormone levels
• A single, benign thyroid lump in a young patient or multiple thyroid lumps in an older patient
• Benign overgrowths projecting from the colon (i.e., polyps, usually in association with acromegaly)
• Elevated prolactin levels (usually mild and almost always combined with acromegaly)
• A family history of cancer, particularly of the thyroid, colon, pancreas, or ovary, or a family history of multiple other noncancerous or cancerous tumors

Tests to screen for Carney complex

Screening for Carney complex must be thorough to cover all locations where Carney complex tumors may grow, such as the heart, the endocrine system, and the reproductive organs. These screening tests can include:^1,2

Imaging tests

• Ultrasound, which uses sound to create a picture of the inside of the body
  • This includes an echocardiogram (EKG or ECG), an ultrasound of the heart.
• Magnetic resonance imaging (MRI) scan
• Computerized tomography (CT or CAT) scan

Blood tests to measure

• Adrenal gland hormones (including cortisol), growth hormone, prolactin, IGF-1, and adrenocorticotropic hormone (ACTH)
• Thyroid hormones, including thyroid-stimulating hormone and free thyroxine
• Levels of reproductive hormones, including luteinizing hormone, and follicle-stimulating hormone

Other tests

• 24-hour urine test for cortisol, creatinine, and 17-hydroxysteroids
• Dexamethasone suppression test (Liddle test)
• Salivary test for cortisol
• Oral glucose test

The specific type of screening test used for Carney complex often depends on the person’s age and symptoms and whether healthcare providers find tumors. For example, a person who has not yet gone through puberty may get different tests than someone who is older. Additional tests may also be needed if tumors are detected or suspected, to determine their location and size.

Genetic testing

Once a healthcare provider determines through screening whether the person meets the clinical criteria for Carney complex, the provider might recommend genetic testing from a commercial laboratory. Certain people who meet the clinical criteria for Carney complex may not test positive for a PRKAR1A mutation. This does not mean they do not have Carney complex. They may either have a mutation that was not identified by the available technology or have a mutation in another gene or chromosome.

Although there is currently no way to prevent tumors from growing in Carney complex, regular monitoring with imaging and other tests can help identify problems early so that treatment can begin.

Treatments for symptoms of Carney complex include medication and surgery.^1,2

If a tumor is not causing any symptoms, as is usually the case with thyroid adenomas, treatment may not be needed.

Tumors that cause only mild symptoms or that cause hormone imbalances, such as pituitary tumors, may be treatable with medication. However, for cardiac tumors and tumors on endocrine glands, surgery to remove the tumors may be the best option. A combination of treatments may also be effective.

In the rare instances that a tumor develops into cancer, also called a carcinoma, surgery is usually required. Radiation and medication are also used to treat carcinomas.

The Importance of Ongoing Screening in Carney Complex

In Carney complex, tumors can grow at any time. Therefore, ongoing screening for new tumors is an important part of standard care for someone diagnosed with Carney complex. The type of screening test and the frequency differ slightly depending on the age of the person when they are diagnosed.

Healthcare providers suggest the following screening tests and frequency. Please note that these suggestions are general and should not be interpreted as care recommendations. If you have specific questions about Carney complex in yourself or your child, please consult a healthcare provider.

Before Puberty

After Puberty