Carney Complex – Definition
The Carney complex (CNC) describes a rare cancer predisposition syndrome that leads to the development of characteristic pigment spots, multiple myxomas, hormonal tumors or regulatory disorders, and malignant neoplasms.
Synonyms:
Familial myxoma syndrome, Carney syndrome
Gene:
PRKAR1A (protein kinase A-regulating subunit 1α)
Gene product:
PRKAR1A
Function:
Tumor suppressor gene
Pattern of inheritance:
Autosomal dominant
Prevalence:
Approximately 750 patients with CNC are recorded worldwide; the prevalence is unknown.
Genotype-phenotype correlation:
Unknown
Penetrance:
70-80 %
Carney Complex – Diagnosis
The diagnosis is made on the basis of the following diagnostic criteria:
Main Criteria
- Mottled pigment abnormalities of the skin (with typical localization on the lips, corners of the eyes, conjunctiva, vaginal/penile mucosa)
- Myxomas of the skin, mucosa, or heart
- Myxomatosis of the breast (or evidence of this on MRI)
- Primary pigmented nodular adrenocortical disease (PPNAD) or corresponding indications in the dexamethasone inhibition test
- Acromegaly due to GH-secreting pituitary adenoma
- Thyroid carcinoma (at any age) or multiple hypothyroid nodules (before puberty)
- Large cell calcifying Sertoli cell tumor (LCCSCT) (or characteristic calcifications in testicular tissue)
- Psammomatous melanotic schwannomas (PMS)
- Blue nevus, multiple epithelioid blue nevi
- Osteochondromyxomas
Supplementary Criteria
- A first-degree relative with Carney complex (CNC)
- Evidence of an inactivating PRKAR1A mutation
Differential Diagnoses
- Peutz-Jeghers syndrome
- Leopard syndrome
- PTEN hamartoma tumor syndrome
- McCune-Albright syndrome
- Familial generalized lentiginosis
Clinical Presentation
Clinical Anomalies
Carney complex mutation carriers are characterized by the frequent occurrence of skin changes, myxomas (cardiac, cutaneous), and an increased risk of endocrine and non-endocrine tumors and schwannomas, among other things. Characteristic are the dull brown to black skin lesions(lentigines), some present at birth and multiply during puberty. The average age of onset is 20 years.
Over 70% of CNC patients develop their first myxomas at a young age, and they are usually found in the cardiac region. However, myxomas can also affect the skin, breast, oropharynx, bones, and female genital tract. As cardiac myxomas account for around 50% of deaths, regular cardiological examinations are essential.
Endocrine Tumors
- Primary adrenocortical dysplasia with pigmented nodules, which causes ACTH-independent Cushing’s syndrome, is the most common endocrine tumor with a prevalence of 25-60%.
- Over 10% of patients have pituitary adenomas that lead to acromegaly due to GH secretions. In 75%, however, asymptomatic increases in the following laboratory parameters occur GH, IGF-1, or prolactin in serum and elevated oral glucose tolerance test.
- Testicular tumors (Sertoli cell tumor, Leydig cell tumor) affect 30-50% of men. Although the majority of these tumors are benign, 17% are malignant.
- Thyroid tumors (non-medullary carcinoma, follicular hyperplasia, cysts) develop in less than 10% of patients, but thyroid nodules are present in the majority of CNC patients.
- Psammomatous melanotic schwannomas (PMS), a rare tumor of the nerve sheaths, occur in approx. 10% of CNC patients, mainly in the gastrointestinal tract, borderline cord, or thoracic wall, develop malignant degeneration in approximately—10%.
Special Features of Treatment
Treatment of the Carney complex is primarily symptomatic and should be carried out by a professional, multidisciplinary team.
Surgical removal of cardiac myxomas is essential. Furthermore, an adrenalectomy is recommended for PPNAD or adrenolysis with medication.
In the case of a pituitary tumor, surgical removal of a pituitary tumor or treatment of acromegaly with somatostatin analogs is recommended.
Schwannomas are more complex to treat due to infiltrative growth around nerves/nerve roots and metastasis to the lungs, liver, and brain.
The screening examinations listed below, compiled by experts, are particularly important for detecting tumors early and successfully treating them.
Diagnosis ofCarney ComplexWhat's Next?
Once diagnosed, it is recommended that a cancer predisposition specialist manage the patient. The following section explains whether cancer screening tests or other measures are necessary and how they should be performed. Some additional information, including links to support groups, is also included at the end of this page.
Diagnosis ofCarney ComplexWhat's Next?
Once diagnosed, it is recommended that a cancer predisposition specialist manage the patient. The following section explains whether cancer screening tests or other measures are necessary and how they should be performed. Some additional information, including links to support groups, is also included at the end of this page.
Recommendations for Early Detection in Your Patients
- Annual echocardiography from childhood onwards
- Regular skin examinations
- Regular determination of blood sugar, cortisol in urine, serum ACTH, serum cortisol, growth hormone, insulin-like-growth-factor I, prolactin, GH-, from adolescence, if necessary, further examinations for Cushing’s syndrome
- Screening for thyroid tumors
- CT of the adrenal glands for the detection of PPNAD
- MRI of the pituitary gland
- MRI of brain/spine/thorax/abdomen/retroperitoneum/pelvis for PMS detection
- In men, annual sonographic examination of the testes from childhood onwards
- In women, transabdominal sonographic examination of the ovaries at least once
- In prepubertal children, monitoring of longitudinal growth and pubertal development
Carney Complex – Further Information
Additional Resources
Unfortunately, we are currently not aware of any support groups for individuals with Carney Complex. New information will be added as soon as it becomes available.
