Carney Complex (CNC) is a rare syndrome characterized by spotty skin pigmentation and multiple neoplasms, notably cardiac myxomas, schwannomas, and endocrine tumours. It is often inherited in an autosomal dominant manner with PRKAR1A gene mutations found in the majority of cases. Male infertility is established as part of the CNC phenotype and is largely associated with Large cell calcifying Sertoli cell tumours (LCCSCT). We describe a case of a 30-year-old male patient with Carney Complex, presenting with severe oligoasthenozoospermia and primary pigmented nodular adrenocortical disease (PPNAD). During follow-up consults, the severe oligozoospermia and impaired semen motility persisted and the patient was also diagnosed with a recurring cardiac myxoma and LCCSCT. Molecular testing identified a novel PRKAR1A mutation involving a deletion of exons 4 to 7. Our findings suggest this mutation causes PRKAR1A haploinsufficiency, which may be directly linked to male infertility, irrespective of the presence of testicular tumours. Accordingly, in male patients with CNC, detection of a PRKAR1A gene mutation may serve as a predictive marker for infertility. This case report illustrates the importance of early consideration and management of infertility in male patients diagnosed with CNC.
Keywords: Carney complex; LCCSCT; PPNAD; PRKAR1A gene deletion; PRKAR1A haploinsufficiency; male infertility; oligoasthenozoospermia.
Male infertility associated with a novel PRKAR1A mutation in carney complex Carney Complex (CNC) is a rare genetic disorder that leads to the development of various tumours, including in the heart and endocrine glands. Most cases are linked to mutations in a gene called PRKAR1A and are inherited in an autosomal dominant manner. This case report presents a detailed examination of a patient diagnosed with Carney Complex (CNC), followed over nearly 10 years. The patient initially consulted due to infertility, which led to extensive investigations and diagnosis of several type of tumours: Primary pigmented nodular adrenocortical disease (PPNAD) in the adrenal glands, a cardiac myxoma, and Large cell calcifying Sertoli cell tumours (LCCSCT) in the testes - all tumours are characteristic features of CNC. Notably, genetic testing revealed a novel mutation in the PRKAR1A gene. Through this case, we highlight how this genetic mutation might cause PRKAR1A haploinsufficiency and be solely responsible for infertility in CNC irrespective of testicular tumours, providing valuable insights into a condition where male infertility is rarely documented. This report contributes important new information to the limited existing research on the connection between CNC and male infertility.
© The Author(s) 2024.