Presentation: Patient with Carney complex

A 26-year-old man presents with signs of mild acromegaly and a history of cardiac myxoma, for which he had an operation at the age of eight. There is no known family history of a tumour syndrome.

Genomic testing should be considered if a patient presents with two or more of the features from the following list, with histological confirmation where relevant, or one feature from the list below and an affected first-degree relative:

• spotty skin pigmentation with typical distribution (lips, conjunctiva, vaginal and penile mucosa);
• myxoma (cutaneous and mucosal);
• cardiac myxomas;
• breast myxomatosis (or fat-suppressed MRI suggestive of this finding);
• primary pigmented nodular adrenocortical disease or a paradoxical positive response of urinary glucocorticosteroid (cortisol) excretion to dexamethasone administration during a Liddle test;
• acromegaly due to growth hormone-producing adenoma;
• large cell calcifying sertoli cell tumour or characteristic calcification on testicular ultrasound;
• thyroid carcinoma or multiple hypoechoic nodules on thyroid ultrasound in a young patient;
• psammomatous melanotic schwannomas;
• blue nevus or epithelioid blue nevus;
• breast ductal adenoma; and
• osteochondromyxoma.

• Consult the National Genomic Test Directory. From here you can access the rare and inherited disease eligibility criteria for information about individual tests and their associated eligibility criteria. You can also access a spreadsheet containing details of all available tests.
  • For those working within NHS Wales, please consult the All Wales Medical Genomics Service website for information on how to arrange testing.
• To find out which genes are included on different gene panels, see the NHS Genomic Medicine Service (GMS) Signed Off Panels Resource.
• For patients presenting with Carney complex, the R156 Carney complex panel is appropriate. This includes PRKAR1A single gene testing. Loss-of-function variants are expected, but if test results are negative it is recommended that the case be taken to a multi-disciplinary team in order to consider somatic testing for mosaicism, PRKACB gene testing or exome sequencing (all subject to availability).
• The following panels also contain the PRKAR1A gene:
  • R217 Multiple endocrine neoplasia;
  • R236 Pigmentary skin disorders;
  • R160 Primary pigmented nodular adrenocortical disease; and
  • R359 Tumour predisposition (childhood onset panels).
• Note that de novo variants are present in up to 30% of cases of Carney complex, and that large deletions in the PRKAR1A gene are associated with a more severe phenotype.
• None of the tests outlined above include whole genome sequencing, so you should use your local Genomic Laboratory Hub test order and consent (record of discussion) forms.
• The majority of these tests are DNA based, and an EDTA sample (purple-topped tube) is required. The sample is best stored at four degrees Celsius until it can be posted to the genomic laboratory.
• Information about patient eligibility and test indications was correct at the time of writing. When requesting a test, please refer to the National Genomic Test Directory to confirm the right test for your patient.

For clinicians

• NHS England: National Genomic Test Directory

For patients

• Association for Multiple Endocrine Neoplasia Disorders (AMEND)
• National Organization for Rare Diseases: Carney complex