Endocrine Abstracts

Background: Various genetic syndromes have identified distinct and consistent behavior patterns. Carney complex (CNC) is a rare multiple endocrine neoplasia syndrome first described by Dr Carney in 1985 as a complex of myxomas (cardiac, skin), spotty skin pigmentation, and endocrine over activity. CNC is caused by mutations of the PRKARIA gene that encodes the RIα regulatory subunit of Protein kinase A (PKA). We recently reported that a Prkar1a heterozygote mouse that was developed in our lab showed brain region-specific increased PKA activity that was associated with anxiety-like behavioral phenotype. We investigated the behavioral and clinical phenotype of adults and children with CNC.

Methods: Chart review of 56 adults and 50 children evaluated on CNC protocol.

Results: Sixty-seven percent of adults with PRKAR1A mutations were diagnosed with a psychiatric disorder compared to 29% of adults with clinical features of CNC who were negative for PRKAR1A mutation (P<0.01). Fourty-three percent of pediatric patients with PRKAR1A mutations were diagnosed with a psychiatric disorder compared to 11% of children with clinical features of CNC who were negative for PRKAR1A mutation (P<0.02). The most frequent psychiatric diagnosis in adults with PRKAR1A mutation were: anxiety, depression, and bipolar disorder (in that order), while for children with PKKAR1A mutation were: learning difficulties, attention deficit hyperactivity disorder, anxiety, and depression (in that order). For adults, PRKAR1A mutation was associated with a higher clinical severity score (CSS) (P<0.01), but there was no correlation between CSS and a diagnosis of psychiatric disorder.

Clinical Implications: Somatization is common with chronic illness. Behavioral patterns associated with known genetic alterations are useful to provide anticipatory guidance from an educational, rehabilitative, and parenting perspective. It appears that PRKAR1A inhibition in humans and Prkar1a-down-regulation in mice is associated with increased risk for psychopathology, consistent with the importance of this protein in cAMP/PKA signaling in brain function.