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. 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 is a disorder characterized by an increased risk of several types of tumors. Affected individuals also usually have changes in skin coloring (pigmentation). Signs and symptoms of this condition commonly begin in the teens or early adulthood.

Individuals with Carney complex are at increased risk of developing noncancerous (benign) tumors called myxomas in the heart (cardiac myxoma) and other parts of the body. Cardiac myxomas may be found in any of the four chambers of the heart and can develop in more than one chamber. These tumors can block the flow of blood through the heart, causing serious complications or sudden death. Myxomas may also develop on the skin and in internal organs. Skin myxomas appear as small bumps on the surface of the skin or as lumps underneath the skin. In Carney complex, myxomas have a tendency to recur after they are removed.

Individuals with Carney complex also develop tumors in hormone-producing (endocrine) glands, such as the adrenal glands located on top of each kidney. People with this condition may develop a specific type of adrenal disease called primary pigmented nodular adrenocortical disease (PPNAD). PPNAD causes the adrenal glands to produce an excess of the hormone cortisol. High levels of cortisol (hypercortisolism) can lead to the development of Cushing syndrome. This syndrome causes weight gain in the face and upper body, slowed growth in children, fragile skin, fatigue, and other health problems.

People with Carney complex may also develop tumors of other endocrine tissues, including the thyroid, testes, and ovaries. A tumor called an adenoma may form in the pituitary gland, which is located at the base of the brain. A pituitary adenoma usually results in the production of too much growth hormone. Excess growth hormone leads to acromegaly, a condition characterized by large hands and feet, arthritis, and "coarse" facial features.

Some people with Carney complex develop a rare tumor called psammomatous melanotic schwannoma. This tumor occurs in specialized cells called Schwann cells, which wrap around and insulate nerves. This tumor is usually benign, but in some cases it can become cancerous (malignant).

Almost all people with Carney complex have areas of unusual skin pigmentation. Brown skin spots called lentigines may appear anywhere on the body but tend to occur around the lips, eyes, or genitalia. In addition, some affected individuals have at least one blue-black mole called a blue nevus.

Most tumors in Carney complex are noncancerous (also called benign). However, people with Carney complex have a higher risk than people without Carney complex for certain types of cancer.

Cancerous (or malignant tumors)—called carcinomas—most associated with Carney complex include liver, ovarian, testicular, and pancreatic cancer. In rare cases, Carney complex is associated with thyroid cancer and cancer of the cells around nerves.

But Carney complex itself is not cancer.

It can.

In females, Carney complex may cause abnormal hormone levels or cysts on the ovaries, which can affect menstruation and ovulation and, therefore, fertility.

In males, Carney complex can cause large-cell calcifying Sertoli cell tumors in the testes. Larger tumors in the testes may block the sperm tubules or cause hormone imbalances that result in infertility.

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

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.

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.

Connective Tissues (Myxomas)

Myxomas are noncancerous growths of the body’s connective tissue, including skin and muscle. They grow anywhere in the body except the hands and feet.

Skin (cutaneous) myxomas

Myxomas on or under the skin are small and colorless. They may appear in infancy and grow in areas such as the eyelids, ear canals, mouth, throat, nipples, and female genital area. They usually do not have symptoms associated with them. People with Carney complex who have skin myxomas may also have heart myxomas.

Heart (cardiac) myxomas

Myxomas on the heart or in the heart’s chambers may grow in people of all ages with Carney complex. Large cardiac myxomas can cause blood clots, uneven heart rhythm, or heart failure and other complications, such as stroke. Surgery may be needed to remove cardiac myxomas to prevent these problems. Cardiac myxomas may cause up to one-quarter of deaths in people with Carney complex.

Breast myxomas

Myxomas of the breast are very common among females with Carney complex, and they often grow in both breasts. A special type of imaging test helps healthcare providers tell the difference between myxomas and other breast lumps to prevent unneeded biopsies.

Endocrine Glands

Endocrine glands make hormones, chemical messengers that tell other body organs what to do and when to do it.

Adrenal glands

Adrenal glands, a pair of walnut-sized organs above the kidneys, release hormones to control different body functions. Adrenal gland tumors are usually functioning, meaning they make hormones, which leads to different symptoms.

Cushing syndrome occurs when the adrenal glands make too much cortisol. Symptoms syndrome can include obesity above the waist (but with thin arms), a round face, skin changes, weak bones and muscles, and slow growth rate in children.

Carney complex tumors on the adrenal glands, called primary pigmented nodular adrenocortical disease (PPNAD), can also lead to Cushing syndrome. PPNAD-caused Cushing syndrome may have no symptoms or may have symptoms that come and go. If untreated, PPNAD can also cause hypertension (high blood pressure), diabetes (high blood sugar), osteoporosis (weak bones), or slow growth in children.

There are other adrenal gland disorders in addition to Cushing syndrome and PPNAD.

Thyroid gland

Carney complex may cause nodules (lumps) on the thyroid that appear as small cysts or fluid-filled sacs on ultrasound. Nodules can grow into larger adenomas, so it is important to monitor them closely. Some symptoms of thyroid adenomas include weight loss, excessive sweating, and fatigue. In rare cases, thyroid adenomas may develop into thyroid cancer in people with Carney complex.

Pituitary gland

This tiny organ at the base of the brain controls growth, stress response, reproductive functions, and other vital body activities. Tumors on the pituitary gland, called adenomas, occur in about 1 in 10 people with Carney complex.

These adenomas are often functioning, leading to too much hormone, and the symptoms differ depending on the hormone being overproduced. For example, too much growth hormone causes gigantism or acromegaly, a type of excess growth. In girls and women, too much prolactin causes the menstrual cycle to stop.

Reproductive Organs

Testicular tumors, called large-cell calcifying Sertoli cell tumors (LCCSCT), occur in about one-third of males with Carney complex. LCCSCTs are small deposits of calcium that may look hardened, like bone, on an ultrasound of the testicles. LCCSCTs are almost always benign and may cause precocious (early) puberty or breast tissue enlargement (gynecomastia). Depending on their size, LCCSCTs may interfere with fertility by blocking the tubules that transport sperm. LCCSCTs may also cause the testes to become unusually large, a condition called macroorchidism.

Although it is not very common, females with Carney complex may have cysts on their ovaries or growths in the milk ducts of the breast, called ductal adenomas. In very rare cases, ovarian cysts may develop into ovarian cancer.

Nerves and Bones

Nerve cells are surrounded with insulating cells called Schwann cells. When Carney complex affects Schwann cells, growths that look like bundles of nerve cells appear in scans. These growths are called psammomatous melanotic schwannomas. They appear most often in the intestinal tract and along the spinal nerves and may cause pain or discomfort.

An osteochondromyxoma (tumor of the bone) may also occur in patients with Carney complex.

Both tumor types are rare and occur in only a small number of people with Carney complex.

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.

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.

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.

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.

Normal Function

The PRKAR1A gene provides instructions for making one part (subunit) of an enzyme called protein kinase A. This enzyme promotes cell growth and division (proliferation). Protein kinase A is made up of four protein subunits, two of which are called regulatory subunits because they control whether this enzyme is turned on or off. The PRKAR1A gene provides instructions for making one of these regulatory subunits, called type 1 alpha. Protein kinase A remains turned off when the regulatory subunits are attached to the other two subunits of the enzyme. In order to turn on protein kinase A, the regulatory subunits must break away from the enzyme.

Health Conditions Related to Genetic Changes

Carney complex

More than 117 mutations in the PRKAR1A gene have been found to cause Carney complex. Most of these mutations result in an abnormal type 1 alpha regulatory subunit that is quickly broken down (degraded) by the cell. The lack of this regulatory subunit causes protein kinase A to be turned on more often than normal, which leads to uncontrolled cell proliferation. The signs and symptoms of Carney complex are related to the unregulated growth of cells in many parts of the body.

Other Names for This Gene

• cAMP-dependent protein kinase regulatory subunit RIalpha
• cAMP-dependent protein kinase type I-alpha regulatory chain
• CAR
• CNC1
• DKFZp779L0468
• KAP0_HUMAN
• MGC17251
• PKR1
• PPNAD1
• PRKAR1
• protein kinase A type 1a regulatory subunit
• protein kinase, cAMP-dependent, regulatory subunit type I alpha
• protein kinase, cAMP-dependent, regulatory, type I, alpha
• protein kinase, cAMP-dependent, regulatory, type I, alpha (tissue specific extinguisher 1)
• tissue-specific extinguisher 1
• TSE1

Genomic Location

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:

• 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:

• 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:

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.

In some cases, yes. Pregnant people diagnosed with Carney complex and those who have tested positive for the genetic mutation can work with a healthcare provider to get prenatal testing for Carney complex.

People with Carney complex may also want to talk with a genetic counselor before they try to start a family to discuss the possibility of passing the genetic mutation to their children and to discuss options if they find it difficult to conceive naturally.

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.

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