Carney complex (CNC) is a multifaceted disorder with a spectrum of clinical and genetic presentations that affects individuals of diverse ethnic and racial backgrounds. Most commonly CNC patients exhibit atypical skin pigmentation, cutaneous and/or cardiac myxomas, growth hormone excess, and primary pigmented nodular adrenal disease (PPNAD) which is a cause of ACTH-independent Cushing syndrome or hypercortisolism. Diagnosis usually occurs around 20 year- of-age, with a higher incidence in females compared to males. CNC is most commonly due to pathogenic variants in PRKAR1A gene (CNC locus 1), which encodes the type I alpha regulatory subunit of protein kinase A (PKA). CNC locus 2 is caused a yet unidentified gene in the 2p16 region. Most commonly PRKAR1A pathogenic variants result in haploinsufficiency with subsequent constitutive activation of PKA. When familial, CNC is inherited in an autosomal dominant manner with almost complete penetrance but can also be sporadic.
PRKAR1A