Maternally inherited PRKAR1A pathogenic variant causing Carney complex with a concomitant LDLR variant resulting in hyperlipidemia: a case report

Objective Carney complex (CNC) is an autosomal dominant multisystem tumor syndrome predominantly caused by pathogenic PRKAR1A mutations. Cardiac myxoma, multiple endocrine neoplasms and cutaneous pigmented lesions are its typical clinical manifestations. We report an extremely uncommon case of CNC caused by a PRKAR1A pathogenic variant, with a LDLR variant leading to familial hyperlipidemia and marked phenotypic heterogeneity within the family. Case presentation A 45-year-old male presented with palpitations was admitted to our hospital. The patient’s past medical history included cerebral infarction, myocardial infarction, right monocular blindness, and atrial myxoma. Physical examination revealed typical acromegalic facies, accompanied by markedly elevated serum growth hormone (GH) levels. Pituitary magnetic resonance imaging (MRI) further identified a pituitary neuroendocrine tumor. Transthoracic echocardiography and contrast-enhanced cardiac magnetic resonance (CMR) with late gadolinium enhancement (LGE) demonstrated global cardiac chamber enlargement and ventricular hypertrophy. Coronary CTA revealed diffuse dilatation of the coronary artery. Genetic testing confirmed two maternally inherited pathogenic variants: the splice-donor variant PRKAR1A c.769 + 1G>A responsible for CNC, and LDLR c.1879G>A, which causes familial hypercholesterolemia. One month after discharge from our hospital, the patient received transnasal transsphenoidal resection of sellar pituitary lesion under general anesthesia at the Department of Neurosurgery in another general hospital. Preoperative GH and insulin-like growth factor 1 (IGF-1) were elevated on repeat testing, and both decreased significantly postoperatively. The sellar lesion was confirmed as a plurihormonal pituitary neuroendocrine tumor of pituitary transcription factor 1 (PIT-1) lineage; immunohistochemistry showed weak GH expression, focal prolactin (PRL) and luteinizing hormone (LH) expression, negative adrenocorticotropic hormone(ACTH) and T-box pituitary transcription factor(T-PIT) staining, with a Ki-67 labeling index of ~1%. Conclusion The splice-site variant PRKAR1A c.769 + 1G>A represents a well-documented recurrent pathogenic variant among patients with CNC. The majority of previously reported carriers develop primary pigmented nodular adrenocortical disease (PPNAD) and overt Cushing syndrome. However, our patient presented with acromegaly driven by a plurihormonal PIT-1-lineage pituitary neuroendocrine tumor without corticotroph differentiation. accompanied by atrial myxoma, cardiac hypertrophy, cardiomegaly, coronary dilatation, and familial hypercholesterolemia secondary to an LDLR mutation. This rare coexisting genetic phenotype underscores the value of prompt genetic and endocrine screening for at-risk patients.