Carney Complex

Approved by the Lineagotica Editorial Board, 12/2016

What is Carney complex?

Carney complex is a hereditary condition associated with spotty skin pigmentation; myxomas, which are benign (noncancerous) connective tissue tumors; and cancerous tumors of the endocrine (hormone-producing) glands. Tumors can be benign or cancerous. A benign tumor means 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 typically develop when a person is in childhood or his or her early 20s. Skin pigmentation and heart myxomas or other heart problems are usually the first signs of the condition. The spotty skin pigmentation is found on lips, inner and outer corners of the eyes, the conjunctiva (membrane lining) of the eye, and around the genital area. Other common features of Carney complex are Cushing’s syndrome and multiple thyroid nodules (tumors).  Cushing’s syndrome in Carney complex is always due to primary pigmented nodular adrenocortical disease (PPNAD) and features a combination of weight gain, high blood pressure, diabetes, and easy bruising, caused by the overproduction of the hormone cortisol. Although people with Carney complex have an increased risk of cancer, most tumors are benign. Cancers associated with Carney complex include liver, ovarian, testicular and pancreatic cancer, and a rare tumor of the nervous system called “schwannoma” that can sometimes be cancerous and very aggressive.

Carney complex is also referred to as:

  • NAME syndrome – Nevi, meaning birthmarks or moles, Atrial myxoma, Myxoid neurofibromas, and Ephelides (freckles)

  • LAMB syndrome – Lentigines, Atrial Myxoma, and Blue nevi

What causes Carney complex?

Carney complex is a hereditary genetic condition that may be inherited in an autosomal dominant manner or occur sporadically.  This means that the risk of developing cancer and other features of Carney complex can be passed from generation to generation in a family through gene(s) mutations (alterations). In particular, researchers have learned more about how the gene called PRKAR1A is associated with Carney complex, through its involvement with regulating the body’s cell signaling with protein kinase A (PKA). Researchers believe that more than 70% of people with Carney complex, and 80% of patients with 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 area that contains it. To date, more than 130 different PRKAR1A mutations have been found.  Most of the mutations are unique, meaning they are identified in single families only. So far, no strong association between a particular genetic mutation type and certain symptoms of Carney complex, such as cancer, has been seen.

People without a mutation in the PRKAR1A gene typically start to show mild symptoms later in life. These people less frequently have other family members affected by Carney complex. The gene mutation in that person is considered sporadic, meaning it occurs by chance.

A second genetic defect associated with Carney Complex has been described in a 10MB region in chromosome 2 (2p16), but the genes responsible for the phenotype are still unknown.  Recently, mutations in the PRKACB gene were found in a single person with Carney complex and also in young children with Cushing syndrome that had no other symptoms of Carney complex. Mutations in the PDE11A and PDE8B genes have also been found in younger people with Cushing syndrome but their link to Carney complex remains in question. The search for other genes that might be associated with Carney complex continues. Mutations of another related gene (PRKACA) involved in PPNAD and other types of Cushing’s syndrome do not appear to cause Carney complex.

How is Carney complex inherited?

Normally, every cell has 2 copies of each gene: 1 inherited from the mother and 1 inherited from the father. Carney complex follows an autosomal dominant inheritance pattern, in which a mutation happens in only 1 copy of the gene. This means that a parent with a gene mutation may pass along a copy of their normal gene or a copy of the gene with the mutation. Therefore, a child who has a parent with a mutation has a 50% chance of inheriting that mutation. A brother, sister, or parent of a person who has a mutation also has a 50% chance of having the same mutation.   However, if the parents of the proband are negative for the mutation, the risk to the siblings significantly decresases but does not go back to population risk.

Options exist for people interested in having a child when a prospective parent carries a gene mutation that increases the risk for this hereditary cancer syndrome. Preimplantation genetic diagnosis (PGD) is a medical procedure done in conjunction with in-vitro fertilization (IVF). It allows people who carry a specific known genetic mutation to have children who do not carry the mutation. A woman’s eggs are removed and fertilized in a laboratory. When the embryos reach a certain size, 1 cell is removed and is tested for the hereditary condition in question. The parents can then choose to transfer embryos which do not have the mutation. PGD has been in use for over 2 decades, and has been used for several hereditary cancer predisposition syndromes. However, this is a complex procedure with financial, physical, and emotional factors to consider before starting. For more information, talk with an assisted reproduction specialist at a fertility clinic.

How common is Carney complex?

Carney complex is very rare. About 750 cases have been reported worldwide. It is estimated that between 60% and 75% of cases of Carney complex run in families. The remaining 25% to 40% of cases appear to be sporadic and may be due to a de novo, meaning new, gene mutation.

How is Carney complex diagnosed?

Carney complex is diagnosed when a person has at least 2 of the 12 major features listed below. People who have a close family member, meaning a parent, sibling, or child, already diagnosed with Carney complex are considered to be affected if they have at least 1 of the features listed.

Major diagnostic features for Carney Complex

  • Spotty skin pigmentation with specific pattern and locations

  • Myxoma (benign tumors)

  • Heart myxoma

  • Breast myxomatosis

  • Breast ductal adenomas

  • PPNAD or abnormal result of urine test called Liddle’s test, related to Cushing’s syndrome

  • Acromegaly, an increased size of hands, feet, and face due to a pituitary tumor

  • Testicular neoplasm called large cell calcifying Sertoli cell tumor (LCCST)

  • Thyroid cancer

  • Psammomatous melanotic schwannoma, meaning tumors that grow on nerves

  • Blue nevi, which are blue-black moles

  • Osteochondromyxoma (bone tumors)

Genetic testing for mutations in the PRKAR1A gene is available for people suspected to have Carney complex. If a patient has a PRKAR1A mutation and 1 of the above tumors or other conditions, then he or she is diagnosed with Carney complex.  Genetic testing for the genes discovered more recently, PRKACA, PRKACB, PDE11A, and PDE8B, is not yet commercially available.

In addition, other physical symptoms have been seen in people with Carney complex. These physical signs may suggest Carney complex, but they are not considered major diagnostic features. Research is ongoing to learn more about these symptoms and their link, if any, to the condition.

  • Significant freckling without darkly pigmented spots or typical pattern

  • Blue nevus, if multiple and confirmed by biopsy

  • Café-au-lait spots, which are light brown spots on skin, or other ‘‘birthmarks’’

  • Abnormal blood test results of high insulin-like growth factor 1 (IGF-I) levels, abnormal glucose tolerance test (GTT), and/or paradoxical growth hormone (GH) response to thyrotropin-releasing hormone (TRH) testing when there is no clinical acromegaly. Also, high levels of a hormone called prolactin in the blood. This is called hyperprolactinemia and is usually paired with acromegaly.

  • Cardiomyopathy, meaning diseases of the heart muscle

  • Pilonidal sinus, which is an abscess in the buttock cleft

  • Extended family history of Cushing’s syndrome, acromegaly, or sudden death

  • Multiple skin tags or other skin lesions called lipomas

  • Polyps, meaning benign growths in the colon, usually along with acromegaly

  • A single, noncancerous thyroid nodule in a younger person, as well as multiple thyroid nodules in an older patient

  • Family history of cancer, in particular of the thyroid, colon, pancreas, and ovary

What are the estimated cancer risks associated with Carney complex?

The risk of cancer is increased in people who have Carney complex, but the specific risk for cancer is unknown. Types of cancer reported in people with Carney complex include adrenocortical carcinoma, pituitary gland tumors, thyroid, colorectal, liver and pancreatic cancers. Ovarian cancer in women and tumors of the testicles in men involving the Sertoli or Leydig cells have also been reported.

What are the screening options for Carney complex?

There are no specific screening guidelines for Carney complex. Suggested screening includes:

  • Yearly echocardiogram, beginning in infancy

  • Regular skin evaluations by a health care professional and self-examinations

  • General endocrine system screening

  • Testicular examinations and/or ultrasound for men

  • Yearly blood tests to check serum levels of cortisol, prolactin, and IGF-1 beginning in adolescence

  • Thyroid gland examinations that may include ultrasound imaging. An ultrasound uses sound waves that create a picture of internal organs.

Screening guidelines may change over time as new technologies are developed and more is learned about Carney complex. It is important to talk with your doctor about appropriate screening tests.

Learn more about what to expect when having common tests, procedures, and scans.

Questions to ask the health care team

If you are concerned about your risk of cancer, talk with your health care team. Consider asking the following questions:

  • What is my risk of developing cancer?

  • What can I do to reduce my risk of cancer?

  • What are my options for cancer screening?

If you are concerned about your family history and think you or other family members may have Carney complex, consider asking the following questions:

  • Does my family history increase my risk of developing cancer?

  • Should I meet with a genetic counselor?

  • Should I consider genetic testing?

More Information

The Genetics of Cancer

Genetic Testing

What to Expect When You Meet With a Genetic Counselor

Collecting Your Family Cancer History

Sharing Genetic Test Results with Your Family

Additional Resources

National Cancer Institute
www.cancer.gov   

American Cancer Society
www.cancer.org  

CancerCare 
www.cancercare.org

To find a genetic counselor in your area, ask your doctor or visit these websites:

National Society of Genetic Counselors
www.nsgc.org

National Cancer Institute: Cancer Genetics Services Directory
http://www.cancer.gov/cancertopics/genetics/directory

National Institutes of Health (NIH) Carney Complex Patient Education Handout (PDF)
http://segen.nichd.nih.gov/documents/Carney_Complex_Pt_Educ_Handout_FINAL.pdf