Carney Complex
Last update: September 2025
Carney complex (CNC; ORPHA:1359; OMIM 160980; MONDO:0008057) is a rare genetic tumour risk syndrome featured by benign myxomas (in more than half of the individuals) affecting the heart, skin and mucosa. Carney complex is also associated with tumours or overactivity of endocrine glands, in particular testis, thyroid, pituitary, and especially adrenal glands, where micronodular pigmented or non-pigmented hyperplasia (PPNAD) is the most common manifestation. Rarely, other neoplasms may occur, such as malignant melanotic nerve sheath tumours. Spotty skin hyperpigmentation (lentigines or blue nevi) is also typical and can be seen around eyes and mouth as well as on the lips. Some features may be evident at birth and the median age at diagnosis is 20 years. CNC 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. Potential differential diagnoses are other phakomatoses such as neurofibromatosis type 1 and PTEN hamartoma tumour syndrome (PHTS).
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.
Pathogenic germline variants in the PRKAR1A gene may also cause isolated familial atrial myxoma (ORPHA:615; OMIM 255960) in some families, where carriers of the genetic alteration present with intracardiac myxoma with no other signs of Carney Complex.
Isolated micronodular pigmented or non-pigmented hyperplasia (PPNAD) may be caused by germline variants of the genes PDE11A and PDE8B.
PRKAR1A-associated diseases are 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) pathogenic variants, meaning there is no prior history of the condition in the family.
Depending on the country there might be options for prenatal testing and preimplantation genetic testing when the causative pathogenic variants are known.
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 (according to Stratakis CA. Carney Complex. 2003 Feb 5 [Updated 2023 Sep 21], not endorsed by ERN GENTURIS):
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), with pharmacological treatment as an alternative. Surgical treatment of other benign manifestations has limited indications and should be discussed case-by-case.
More information regarding Carney complex can be found on:
GeneReviews® - Carney complex
Orphanet: Carney complex
OMIM: Carney Complex type 1
Clingen: Carney Complex type 1
Orphanet: Familial atrial myxoma
OMIM: Familial atrial myxoma
|
Clinical practice guidelines |
ERN GENTURIS care pathway |
ERN GENTURIS patient journey |
ERN GENTURIS publications |
|
Currently unavailable |
Currently unavailable |
Currently unavailable |
Thematic Group 4: Other rare – predominantly malignant – genturis |
ERN GENTURIS webinars - Thematic group 4: Other rare genturis
A list of healthcare providers with expertise in Thematic Group 4: Other rare - predominantly malignant - genturis can be found here.
A non-exhaustive list of patient associations for genetic tumour risk syndromes in EU member states can be found here.