What are the typical treatment approaches for the tumors or other manifestations associated with PRKAR1A gene variants?

Treatment for PRKAR1A-related tumors primarily involves surgical removal, especially for cardiac myxomas to prevent complications like embolism or heart failure. Adrenal tumors (PPNAD) may be managed with medication or surgery depending on their size and hormonal activity. Other manifestations are treated symptomatically, and ongoing surveillance is critical to detect new tumors early.

What are the common early signs or symptoms of Carney complex or PRKAR1A-related tumors that I should be aware of?

Early signs can include changes in skin pigmentation, such as dark spots (lentigines) on the lips, eyelids, or conjunctiva, or blue nevi. Tumors like cardiac myxomas might cause symptoms such as shortness of breath, fatigue, or fainting, while adrenal tumors (PPNAD) can lead to hormonal imbalances, causing weight gain, high blood pressure, or fatigue. Regular monitoring is crucial as symptoms can be subtle.

If I have a PRKAR1A gene variant, what kind of regular medical screenings or monitoring will I need to undergo?

Individuals with a PRKAR1A variant typically require lifelong, multidisciplinary monitoring. This often includes annual echocardiograms to screen for cardiac myxomas, regular endocrine evaluations for adrenal and other hormone-producing tumors, and dermatological exams for skin lesions. Neurological and testicular/ovarian screenings may also be recommended.

Is Carney complex, or the risk of developing PRKAR1A-related tumors, an inherited condition?

Yes, Carney complex is an inherited condition, typically following an autosomal dominant pattern. This means that if one parent has a PRKAR1A gene variant, there is a 50% chance with each pregnancy that their child will also inherit the variant and be at risk for the condition. Genetic counseling is often recommended for affected individuals and their families.

PRKAR1A gene

The PRKAR1A gene encodes a regulatory subunit of protein kinase A, and pathogenic variants are linked to disorders such as Carney complex and acrodysostosis type 1.

Overview

Normal Function

The PRKAR1A gene provides instructions for making one part (subunit) of an enzyme called protein kinase A. This enzyme promotes cell growth and division (proliferation). Protein kinase A is made up of four protein subunits. Two of these subunits are called regulatory subunits because they control whether this enzyme is turned on or off. The PRKAR1A gene provides instructions for making one of these regulatory subunits. Protein kinase A remains off when the regulatory subunits are attached to the other two subunits of the enzyme.

Health Conditions Related to Genetic Changes

Carney complex

Several variants (also called mutations) in the PRKAR1A gene have been found to cause Carney complex, a disorder that is characterized by changes in skin coloring (pigmentation) and an increased risk of various types of tumors. These variants cause cells to produce fewer functioning regulatory subunits for protein kinase A. As a result, protein kinase A is turned on more often than normal, which leads to uncontrolled cell proliferation. The signs and symptoms of Carney complex are related to the unregulated growth of cells in many parts of the body.

Some people with variants in the PRKAR1A gene develop noncancerous (benign) tumors called myxomas in the heart (cardiac myxomas) or a specific type of adrenal tumor called primary pigmented nodular adrenocortical disease (PPNAD). Though these tumors are commonly found in people with Carney complex, some people with PRKAR1A variants develop cardiac myxomas or PPNAD without the additional features of Carney complex.

Other disorders

Variants in the PRKAR1A gene also cause acrodysostosis type 1, a rare skeletal disorder that is characterized by short stature and unusually short fingers and toes (brachydactyly). Affected individuals are often resistant to the effects of several hormones. They may also have bones that grow and develop more quickly and that stop growing sooner than usual (advanced bone age). The PRKAR1A variants that cause acrodysostosis type 1 lead to a decrease in protein kinase A activity, which disrupts cell growth and division and leads to the skeletal abnormalities seen in people with this condition.

Other Names for This Gene

CAR
CNC1
PKR1
PRKAR1
Prkar1alpha
protein kinase A, RI-alpha subunit
protein kinase, cAMP-dependent, regulatory subunit type I alpha
protein kinase, cAMP-dependent, regulatory, type I, alpha
tissue-specific extinguisher 1
TSE1

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Tests of PRKAR1A

Scientific Articles on PubMed

PubMed

Catalog of Genes and Diseases from OMIM

PROTEIN KINASE, cAMP-DEPENDENT, REGULATORY, TYPE I, ALPHA; PRKAR1A

Gene and Variant Databases

NCBI Gene
ClinVar

References

Bertherat J, Horvath A, Groussin L, Grabar S, Boikos S, Cazabat L, Libe R, Rene-Corail F, Stergiopoulos S, Bourdeau I, Bei T, Clauser E, Calender A, Kirschner LS, Bertagna X, Carney JA, Stratakis CA. Mutations in regulatory subunit type 1A of cyclic adenosine 5'-monophosphate-dependent protein kinase (PRKAR1A): phenotype analysis in 353 patients and 80 different genotypes. J Clin Endocrinol Metab. 2009 Jun;94(6):2085-91. doi: 10.1210/jc.2008-2333. Epub 2009 Mar 17. Citation on PubMed or Free article on PubMed Central
Horvath A, Bossis I, Giatzakis C, Levine E, Weinberg F, Meoli E, Robinson-White A, Siegel J, Soni P, Groussin L, Matyakhina L, Verma S, Remmers E, Nesterova M, Carney JA, Bertherat J, Stratakis CA. Large deletions of the PRKAR1A gene in Carney complex. Clin Cancer Res. 2008 Jan 15;14(2):388-95. doi: 10.1158/1078-0432.CCR-07-1155. Citation on PubMed
Kirschner LS, Carney JA, Pack SD, Taymans SE, Giatzakis C, Cho YS, Cho-Chung YS, Stratakis CA. Mutations of the gene encoding the protein kinase A type I-alpha regulatory subunit in patients with the Carney complex. Nat Genet. 2000 Sep;26(1):89-92. doi: 10.1038/79238. Citation on PubMed
Kirschner LS. Use of mouse models to understand the molecular basis of tissue-specific tumorigenesis in the Carney complex. J Intern Med. 2009 Jul;266(1):60-8. doi: 10.1111/j.1365-2796.2009.02114.x. Citation on PubMed
Muhn F, Klopocki E, Graul-Neumann L, Uhrig S, Colley A, Castori M, Lankes E, Henn W, Gruber-Sedlmayr U, Seifert W, Horn D. Novel mutations of the PRKAR1A gene in patients with acrodysostosis. Clin Genet. 2013 Dec;84(6):531-8. doi: 10.1111/cge.12106. Epub 2013 Feb 21. Citation on PubMed
Pereira AM, Hes FJ, Horvath A, Woortman S, Greene E, Bimpaki E, Alatsatianos A, Boikos S, Smit JW, Romijn JA, Nesterova M, Stratakis CA. Association of the M1V PRKAR1A mutation with primary pigmented nodular adrenocortical disease in two large families. J Clin Endocrinol Metab. 2010 Jan;95(1):338-42. doi: 10.1210/jc.2009-0993. Epub 2009 Nov 13. Citation on PubMed or Free article on PubMed Central
Stratakis CA. Carney Complex. 2003 Feb 5 [updated 2023 Sep 21]. In: Adam MP, Bick S, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026. Available from http://www.ncbi.nlm.nih.gov/books/NBK1286/ Citation on PubMed

Genomic Location

The PRKAR1A gene is found on chromosome 17.

Medical Encyclopedia

Genes
Genetics

Understanding Genetics

What is DNA?
What is a gene?
What is a gene variant and how do variants occur?