This test analyzes the PRKAR1A gene, which is the only gene associated with Carney complex. This rare condition is characterized by skin pigmentary abnormalities, myxomas, endocrine tumors, and schwannomas. These findings may be present at birth, although the median age of diagnosis is 20 years.
Genetic testing of this gene may confirm a diagnosis and help guide treatment and management decisions. Identification of a disease-causing variant would also guide testing and diagnosis of at-risk relatives. This test is specifically designed for heritable germline mutations and is not appropriate for the detection of somatic mutations in tumor tissue.
Carney complex is a rare, often inherited condition that is characterized by myxomas (benign tumors of connective tissue), endocrine tumors, schwannomas, and skin pigmentary findings.
Features of this condition may be present at birth, but Carney complex is typically diagnosed in the second decade of life. Skin findings, specifically brown-to-black lentigines, are the most common presenting feature. Cardiac myxomas may occur at a young age. Primary pigmented nodular adrenocortical disease (PPNAD) is the most frequently observed endocrine tumor. The majority of affected individuals have multiple thyroid nodules, most of which are thyroid follicular adenomas. Approximately 10% of affected individuals develop a psammomatous melanotic schwannoma (PMS). Large-cell calcifying Sertoli cell tumors (LCCSCTs) are observed in nearly all affected males, with one-third diagnosed in the first decade of life. Carney complex is diagnosed based on specific clinical criteria or molecular genetic testing.
If a pathogenic variant is identified in the PRKAR1A gene, there is an increased risk of malignancy compared to the average person, but not everyone with such a variant will actually develop cancer. Further, the same variant can present differently, even among individuals within the same family. Because we cannot predict which cancers may develop, most individuals who are found to have a pathogenic variant will be offered various screening tests to detect and prevent cancer. For gene-associated tumor risks, see the table below.
|Primary pigmented nodular adrenocortical disease||Unknown|
|Psammomatous melanotic schwannoma (PMS)||10%|
|Large-cell calcifying Sertoli cell tumors (LCCSCTs)||Nearly 100% in males|
Analysis of the PRKAR1A gene identifies a pathogenic variant in approximately 60%–70% in individuals who meet clinical diagnostic criteria.
Carney complex is inherited in an autosomal dominant manner. Most cases are inherited from a parent, but approximately 30% are the result of a spontaneous de novo mutation.
The prevalence of Carney complex is currently unknown and appears to be rare.
Analysis of the PRKAR1A gene may be considered in individuals with a personal and/or family history of:
Clinical diagnostic criteria for Carney complex have been proposed:
For management recommendations, please refer to:
Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).
Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence in the transcript listed below. In addition, analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any specific limitations in the analysis of these genes are also listed in the table below.
Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.
|Gene||Transcript reference||Sequencing analysis||Deletion/Duplication analysis|