PRKAR1A

Management

Management
CNC is managed by addressing the tumors and complications individually, followed by continual surveillance. Most tumors can be removed surgically, and in some instances, such as select cases of PPNAD or GH-releasing pituitary adenomas, surgical resection can be circumvented with medical therapy, such as a somatostatin analogue for GH excess. Recommended surveillance changes with age but generally includes annual echocardiogram (more frequent in existing myxomas, with or without GH excess), skin examinations, biochemical evaluation of urinary free cortisol (UFC), GH/IGF-1, glucose and HbA1c, and prolactin, along with testicular, thyroid, and trans-abdominal ultrasounds. Patients with CNC may have a normal life span with proper monitoring; however, the average life expectancy is 50 to 55 years-of-age.

Genetic Counselling
Pathogenic variants in PRKAR1A are causative of the majority of cases of CNC and can be inherited in an autosomal dominant manner with near complete penetrance or occur de novo. A carrier of a pathogenic PRKAR1A variant has a 50% chance of transmitting the gene to their offspring. Although identification of a disease-causing variant in PRKAR1A can be used to establish a diagnosis, other genes can also lead to CNC, albeit rarely, including PRKACA (601639), and PRKACB (176892).