What Is Carney Complex? What You Need to Know

What is Carney complex?

Carney complex is an inherited disorder associated with spotty skin pigmentation, myxomas — benign (noncancerous) connective tissue tumors — and a range of other tumors of the endocrine (hormone-producing) glands. Tumors may be benign or cancerous. A benign tumor means that the tumor can grow but will not spread. A cancerous tumor is malignant, meaning it can grow and spread to other parts of the body.

Symptoms of Carney complex usually appear in childhood or the early 20s. Skin pigmentation, cardiac myxomas, or other heart problems are often the first signs of the condition. Spotty skin pigmentation occurs on the lips, at the inner and outer corners of the eyes and the conjunctiva, and in the genital area. Other common features of Carney complex include Cushing syndrome and multiple thyroid nodules. Cushing syndrome in Carney complex is always due to primary pigmented nodular adrenocortical disease (PPNAD), and symptoms caused by overproduction of the hormone cortisol may include weight gain, high blood pressure, diabetes, and easy bruising. Although people with Carney complex have an increased cancer risk, most tumors are benign. Liver, ovarian, testicular, and pancreatic cancer are cancers that may occur in association with Carney complex. A rare nervous system tumor called "schwannoma" may sometimes be cancerous and very aggressive.

Carney complex is also called NAME syndrome or LAMB syndrome.

• NAME syndrome – Nevus (birthmarks or moles), Atrial myxoma, Myxoid neurofibromas, and Epelid (freckles)
• LAMB syndrome – Lentigines, Atrial Myxoma, and Blue (blue) nevus

What causes Carney complex?

Carney complex is an inherited genetic condition that may be inherited in an autosomal dominant manner or arise spontaneously. This means that the risk of developing cancer and other conditions associated with Carney complex can be passed from generation to generation through gene mutations. Research has identified an association between a gene called PRKAR1A and Carney complex through regulation of the body's cell signaling by protein kinase A (PKA). Researchers have reported that more than 70% of people with Carney complex and 80% of patients with pigmented nodular adrenal disease (PPNAD) have a mutation in the PRKAR1A gene (on chromosome 17q24.2), and up to 6% may have deletions in this gene or the chromosomal region containing it. More than 130 different PRKAR1A mutations have been found to date. Most mutations are unique, meaning that they have been identified in only one family. So far, no strong association has been seen between a particular type of genetic mutation and the symptoms of Carney complex (such as cancer).

People without a mutation in the PRKAR1A gene generally begin experiencing mild symptoms later in life. Other family members of these people are less likely to be affected by Cartney complex. The gene mutation in such a person is considered sporadic, meaning that it occurred by chance.

A second genetic cause associated with Carney complex has been identified in a region on chromosome 2 (2p16), but the genes responsible for this phenotype are still unknown. Recently, a PRKACB gene mutation was found in a single person with Carney complex and in young children with Cushing syndrome without other symptoms of Carney complex. Mutations in the PDE11A and PDE8B genes have also been found in young people with Cushing syndrome due to PPNAD, but it is not yet known whether these are linked to Carney complex. Research into other genes that may be associated with Carney complex is ongoing. A mutation in PRKACA, another gene involved in PPNAD and other forms of Cushing syndrome, is not thought to cause Carney complex.

How is Carney complex passed to future generations?

Normally, each cell has 2 copies of a gene, one from the mother and one from the father. Carney syndrome follows an autosomal dominant inheritance pattern, and a mutation in only one copy of a gene is sufficient for it to occur. This means that a parent with a gene mutation may pass a copy of either their normal gene or their mutated gene to their child. Therefore, a child with a parent who has the mutation has a 50% chance of inheriting it. The brother, sister, or parent of someone with a mutation also has a 50% chance of carrying the same mutation. However, if the parents test negative for the mutation (no mutation is found in the test results), the risk to siblings is significantly reduced, although their risk may still be higher than average.

There are options for people with an inherited cancer syndrome who want to have children. Preimplantation genetic diagnosis (PGT), performed together with in vitro fertilization (IVF), is a medical procedure that can allow people to have a child without passing on a particular gene mutation. The woman's eggs are removed and fertilized in a laboratory. When the embryos reach a certain size (approximately 8 cells), 1 cell is removed and tested for the inherited condition in question. The parents may then choose to transfer embryos without the mutation into the woman's uterus. PGT has been used for more than twenty years to prevent various inherited cancer predisposition syndromes. However, it is a complex procedure, and financial, physical, and emotional factors need to be considered before starting PGT.

How common is Carney complex?

Carney complex is rare. Several hundred cases have been reported worldwide. It is estimated that 60% to 75% of Carney complex cases are inherited within families. The remaining 25% to 40% of cases may be sporadic, meaning that they occurred by chance.

How is Carney complex diagnosed?

Carney complex is diagnosed in people who have at least 2 of the 12 major features listed below. People whose parent, sibling, or child has been diagnosed with Carney complex are considered affected if they have at least one of the following features.

Major diagnostic features of Carney complex

• Spotty skin pigmentation with specific patterns and locations
• Myxoma (benign tumors)
• Cardiac myxoma
• Breast myxomatosis
• Breast adenomas
• An abnormal Liddle test result (a urine test related to PPNAD or Cushing syndrome)
• Acromegaly (increased size of the hands, feet, and face due to a pituitary tumor)
• A testicular neoplasm called a large-cell calcifying Sertoli cell tumor (LCCST)
• Thyroid cancer
• Psammomatous melanotic schwannoma (tumors growing in nerve cells)
• Nevi (blue-black moles)
• Osteochondromyxoma (bone tumors)

Genetic tests that can detect mutations in the PRKAR1A gene are available for people suspected of having Carney complex. If someone has a PRKAR1A mutation and at least one of the tumors above, that person is diagnosed with Carney complex. Genetic testing is not yet available for more recently discovered genes such as PRKACA, PRKACB, PDE11A, and PDE8B.

Other physical signs have also been seen in people with Carney complex. These signs may suggest Carney complex, but they are not considered major diagnostic features. Research to learn more about these signs is ongoing, and they are listed below:

• Dark moles or prominent freckling without a specific pattern
• Blue nevus (if there is more than one and confirmed by biopsy)
• Light-brown patches or birthmarks on the skin
• High insulin-like growth factor 1 (IGF-I) levels, an abnormal glucose tolerance test (GTT), and / or paradoxical growth hormone (GH) in response to a thyrotropin-secreting hormone (TRH) test despite the absence of acromegaly. Also, high blood levels of a hormone called prolactin.
• Cardiomyopathy (heart muscle diseases)
• Pilonidal sinus (an abscess in the buttock cleft)
• A family history of Cushing syndrome, acromegaly, or sudden death
• Multiple skin spots or other skin lesions called lipomas
• Polyps (benign growth in the colon, usually with acromegaly)
• A single noncancerous thyroid nodule in a young person and multiple thyroid nodules in an older person
• A family history of cancer (especially thyroid, colon, pancreatic, and ovarian cancer)

What are the estimated cancer risks associated with Carney complex?

People with Carney complex have an increased cancer risk. Cancer types reported in people with Carney complex include adrenocortical (adrenal gland) carcinoma and thyroid, colorectal, liver, and pancreatic cancers. Ovarian cancer in women and testicular tumors involving Sertoli or Leydig cells have also been reported.

What screening options are available for Carney complex?

Recommended screenings are as follows:

• An annual echocardiogram beginning in infancy. Patients who already have a myxoma should have an echocardiogram every 6 months.
• Regular skin examinations by a dermatologist and self-examinations
• Annual blood tests to check serum cortisol, prolactin, and IGF-1 levels, beginning in adolescence
• Ultrasound imaging to assess the thyroid gland
• General endocrine system (hormone-secreting system) screening
• Testicular examinations and ultrasound for males

Screenings may change over time as new technologies are developed and more is learned about Carney complex. You can talk to your healthcare team about appropriate screening tests.

Questions to ask your healthcare team

If you have concerns about your cancer risk, you can talk to your healthcare team. It may be helpful to bring someone to your appointments to take notes. You can ask your healthcare team the following questions:

• What is my risk of developing cancer?
• What can I do to reduce my cancer risk?
• What are my options for cancer screening?

If you have concerns about your family history and think that you or other family members may have Carney complex, you can ask the following questions:

• Does my family history increase my risk of developing cancer?
• Should I see a genetic counselor?
• Should I consider genetic testing?