Carney complex

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Carney complex is a hereditary condition associated with spotty skin pigmentation, myxomas (benign or noncancerous connective tissue tumours), and benign or cancerous tumours of the endocrine glands such as the adrenal, thyroid and pituitary gland. Symptoms of Carney complex typically develop when a person is in 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 (a combination of weight gain, high blood pressure, diabetes, and easy bruising, caused by the overproduction of a specific hormone) and multiple thyroid nodules (tumours) or growth hormone-secreting tumours. Although people with Carney complex have an increased risk of cancer, most tumours are benign.

What causes Carney complex?

Carney complex is a genetic condition. This means that the cancer risk and other features of Carney complex can be passed from generation to generation in a family. Two genes have been associated with Carney complex. They are called PRKAR1A and CNC2. It is believed that about 60% of people with Carney complex have a mutation (alteration) in the PRKAR1A gene and up to 6% may have deletions in this gene. Researchers also believe that other genes may be associated with Carney complex, and studies are ongoing to learn

How is Carney complex inherited?

Normally, every cell has two copies of each gene: one inherited from the mother and one inherited from the father. Carney complex follows an autosomal dominant inheritance pattern, in which a mutation happens in only one 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. In approximately 80 percent of cases, an affected person inherits the mutation from one affected parent. The remaining cases result from new mutations in the gene and occur in people with no history of Carney complex in their family.

Figure 1. Autosomal Dominant inheritance

How common is Carney complex?

Carney complex is very rare. Fewer than 500 cases have been reported worldwide. It is estimated that between 50% and 70% of cases of Carney complex run in families. The remaining 30% to 50% of cases appear to be sporadic (occurs by chance) and may be due to a de novo (new) gene mutation.

How is Carney complex diagnosed?

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

  • Spotty skin pigmentation
  • Myxoma
  • Cardiac myxoma
  • Breast myxomatosis
  • Breast ductal adenomas
  • Cushing’s syndrome
  • Acromegaly (increased size of hands, feet, and face due to a pituitary tumour)
  • Testicular neoplasms
  • Thyroid neoplasms
  • Melanotic schwannoma
  • Blue nevi
  • Osteochondromyxoma

Figure 2. Patient with facial spots typical of Carney complex

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 one of the above tumours or other lesions, then he or she is diagnosed with Carney complex.

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 thyroid, colorectal, and pancreatic cancers. Cancer of the testes (testicles) involving the Sertoli or Leydig cells has also been reported in men.

What are the screening options for Carney complex?

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

  • Yearly echocardiogram (EKG), beginning in infancy
  • Regular skin evaluations
  • Yearly blood tests to check serum levels of cortisol, prolactin, and insulin-like growth factor 1 (IGF-1), beginning in adolescence
  • Thyroid examinations
  • General endocrine system screening
  • Testicular examinations for men

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.