Carney Complex

What is Carney Complex?

Carney complex (CNC, ORPHA: 1359) is a rare genetic tumour risk syndrome associated with multiple tumours, mostly benign (myxomas) affecting the heart, skin and mucosa and multiple endocrine tumours or overactivity of endocrine glands (especially of the testis, thyroid, pituitary, and adrenal glands) and, less frequently, schwannomas as well as other tumours. Abnormal skin pigmentation (lentigines or blue nevi) is also typical. Some features may be evident at birth and the median age at diagnosis is 20 years. The penetrance is near complete at the age of 50 years. More than 750 cases with CNC from diverse ethnic backgrounds have been reported worldwide, but the exact prevalence is unknown. CNC is likely underdiagnosed due to the variability of the disease and insufficient awareness of this rare and complex disorder among the medical community.

What causes Carney complex?

CNC is caused by pathogenic germline variants in the PRKAR1A gene. A pathogenic variant can be detected in more than 80% of patients with a clinical diagnosis. Additional, as yet not identified, genes may be involved in patients with a clinical diagnosis of CNC and negative genetic tests. Germline variants of the genes PDEA11 and PDE8B are involved in isolated micronodular pigmented or non-pigmented hyperplasia (PPNAD), the most common tumour form in CNC.

How is Carney complex inherited?

CNC is inherited in an autosomal dominant pattern, which means that an affected individual has a 50% chance of passing the pathogenic variant to each of their offspring. In about 25% of cases, CNC arises due to spontaneous (de novo) mutation, meaning there is no prior history of the condition in the family.

What are the surveillance options in the EU?

The management of patients diagnosed with CNC includes evaluations following initial diagnosis to assess the extent of the disease and subsequent surveillance recommendations based on age and gender.

Consensus surveillance guidelines for patients with CNC are currently lacking, but expert recommendations include:

Annual echocardiography starting from childhood
Regular skin examinations
Regular clinical examinations, biochemical screening and imaging for (endocrine) tumours (especially pituitary, thyroid, testis) from adolescence onwards
Screening for thyroid tumors
CT-scan of the adrenal glands to detect PPNAD
MRI-scan of the pituitary gland
MRI of the brain/spine/thorax/abdomen/retroperitoneum/pelvis for psammomatous melanotic schwannomas (PMS) detection
Annual sonographic examination of the testes in males starting from childhood
At least one transabdominal sonographic examination of the ovaries in females
Control of growth and puberty development in prepubertal children

These recommendations aim to facilitate early tumour detection and timely interventions to prevent potential complications associated with CNC.

It is crucial to surgically remove cardiac myxomas. Additionally, removal of the adrenal gland (adrenalectomy) should be considered for primary pigmented nodular adrenocortical disease (PPNAD); or alternatively, pharmacological treatment may be considered.

More information regarding Carney complex can be found on:

GeneReviews^® - Carney complex
Orphanet: Carney complex
Uptodate.com: Carney complex

ERN GENTURIS documents

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ERN GENTURIS education

ERN GENTURIS webinars - Thematic group 4: Other rare genturis

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ERN GENTURIS healthcare providers

A list of healthcare providers with expertise in Thematic Group 4: Other rare - predominantly malignant - genturis can be found here.

Patient associations for hereditary cancer syndromes

A non-exhaustive list of patient associations for genetic tumour risk syndromes in EU member states can be found here.