Test Catalog

Test ID: PRKSD    
PRKAR1A Full Gene Sequencing and Deletion/Duplication Analysis, Varies

Useful For Suggests clinical disorders or settings where the test may be helpful

Aiding in the diagnosis of individuals with suspected Carney complex


Aiding in the diagnosis of individuals with suspected acrodysostosis-1 with hormone resistance

Genetics Test Information Provides information that may help with selection of the correct genetic test or proper submission of the test request

This test uses Sanger sequencing to evaluate for the presence of PRKAR1A gene variants associated with Carney complex (CNC), acrodysostosis-1 with hormone resistance, or other PRKAR1A-associated conditions. Additionally, quantitative PCR (qPCR) is used to test for the presence of large deletions and duplications of the PRKAR1A gene.

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Carney complex (CNC) is an autosomal dominant disorder caused by heterozygous germline pathogenic inactivating variants in the PRKAR1A gene. This condition has also been designated by the following acronyms: NAME (nevi, atrial myxomas, ephelides) and LAMB (lentigines, atrial myxoma, blue nevi). CNC is characterized by skin pigmentary abnormalities, myxomas, endocrine tumors, and schwannomas. The most common presenting feature of CNC is unusual skin pigmentation, including brown skin spots called lentigines or blue-black moles called blue nevi. Myxomas are noncancerous (benign) tumors which can occur in the heart (cardiac myxoma), skin, breast, and other internal organs. Cardiac myxomas can occur at a young age, and may block blood flow through the heart, causing serious complications or sudden death. Approximately 25% of affected individuals will develop primary pigmented nodular adrenocortical disease (PPNAD), which can lead to development of Cushing syndrome. Large-cell calcifying Sertoli cell tumors occur in most affected males and may develop in the first decade of life in about one third of cases. Multiple thyroid nodules are present in as many as 75% of affected individuals. Pituitary adenomas resulting in clinically evident acromegaly occur in approximately 10% of adults with CNC. Another 10% of affected individuals have psammomatous melanotic schwannomas, which are typically benign but may be malignant.


PRKAR1A encodes for cAMP-dependent protein kinase type I-alpha regulatory subunit. PRKAR1A functions as a canonical tumor-suppressor gene, with biallelic inactivation in tumors resulting in constitutive activation of protein kinase A. Approximately 70% of individuals with a diagnosis of CNC have an affected parent, while approximately 30% have a de novo pathogenic variant. CNC is a highly penetrant disorder, with approximately 95% of those with a pathogenic PRKAR1A variant developing disease by age 50 years. The proportion of probands with a pathogenic variant detectable by sequence analysis is approximately 60% but can be higher (approximately 80%) in individuals presenting with Cushing syndrome caused by PPNAD. Approximately 10% to 20% of individuals with CNC who test negative for a pathogenic sequence variant may have a large PRKAR1A deletion.


While the majority of reported pathogenic PRKAR1A gene variants are associated with CNC, this gene is also associated with an autosomal dominant condition called acrodysostosis-1 with hormone resistance. This condition is characterized by multiple hormone resistance, short stature, brachycephaly, and short broad hands with short metacarpals and phalanges, among other features. This phenotype results from pathogenic PRKAR1A variants in 1 of the 2 cAMP-binding domains and has a different mechanism of disease than CNC.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided.

Interpretation Provides information to assist in interpretation of the test results

Evaluation and categorization of variants is performed using the most recent published American College of Medical Genetics and Genomics (ACMG) recommendations as a guideline. Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.


Multiple in silico evaluation tools may be used to assist in the interpretation of these results. The accuracy of predictions made by in silico evaluation tools is highly dependent upon the data available for a given gene, and predictions made by these tools may change over time. Results from in silico evaluation tools should be interpreted with caution and professional clinical judgment.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Clinical Correlations:

Some individuals may have a PRKAR1A variant that is not identified by the methods performed (eg, promoter variants, deep intronic variants). The absence of a variant, therefore, does not eliminate the possibility of disease. Genomic regions that are not sufficiently covered for analysis and interpretation will be indicated on the laboratory report.


Test results should be interpreted in context of clinical findings, family history, and other laboratory data. Misinterpretation of results may occur if the information provided is inaccurate or incomplete.


For predictive testing of asymptomatic individuals, it is often useful to first test an affected family member.


Identification of a pathogenic variant in an affected individual allows for more informative testing of at-risk individuals.


Technical Limitations:

If the patient has had an allogeneic blood or bone marrow transplant or a recent (ie, <6 weeks from time of sample collection) heterologous blood transfusion, results may be inaccurate due to the presence of donor DNA. Call 800-533-1710 for instructions for testing patients who have received a bone marrow transplant.


Reclassification of Variants Policy:

At this time, it is not standard practice for the laboratory to systematically review likely pathogenic variants or variants of uncertain significance that have been detected and reported. The laboratory encourages health care providers to contact the laboratory at any time to learn how the status of a particular variant may have changed over time. Consultation with a genetics professional should be considered for interpretation of this result.


A list of benign and likely benign variants detected for this patient is available from the laboratory upon request.


Contact the laboratory if additional information is required regarding the transcript or human genome assembly used for the analysis of this patient's results.

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. Maleszewski JJ, Larsen BT, Kip NS, et al: PRKAR1A in the development of cardiac myxoma. Am J Surg Pathol 2014;38:1079-1087

2. Rhayem Y, Le Stunff C, Abdel Khalek W, et al: Functional characterization of PRKAR1A mutations reveals a unique molecular mechanism causing acrodysostosis but multiple mechanisms causing Carney complex. J Biol Chem. 2015;290(46):27816-27828

3. Salpea P, Horvath A, London E, et al: Deletions of the PRKAR1A locus at 17q24.2-q24.3 in Carney complex: genotype-phenotype correlations and implications for genetic testing. J Clin Endocrinol Metab. 2014;99(1):E183-188

4. Stratakis CA, Raygada M: Carney complex. In: Adam MP, Ardinger HH, Pagon RA, et al. GeneReviews [Internet]. University of Washington, Seattle;2003. Updated August 16, 2018 Accessed September 22, 2021. Available at www.ncbi.nlm.nih.gov/books/NBK1286/

5. OMIM. Carney complex. Johns Hopkins University; Accessed September 22, 2021. Available at www.ncbi.nlm.nih.gov/omim/?term=carney+complex

Special Instructions Library of PDFs including pertinent information and forms related to the test