Infertility as a possible diagnostic feature of Carney complex

Carney complex (CNC) is a rare autosomal dominant syndrome characterized by multiple neoplasms, including endocrine and testicular tumors. Infertility in men with CNC has been rarely reported and remains poorly understood. We describe a 39-year-old male with azoospermia and testicular microlithiasis as the sole manifestations of CNC, without other phenotypic features. Family history revealed CNC-related conditions in his mother and brother, and genetic testing confirmed a pathogenic PRKAR1A variant (c.479_480del; p.Ala160Glufs*5). Testicular biopsy showed hypospermatogenesis with premature spermatocyte and spermatid detachment, consistent with protein kinase A hyperactivation-related apoptosis. Intracytoplasmic sperm injection with retrieved sperm resulted in poor embryonic development, and the couple pursued donor sperm-assisted reproduction. Testicular microlithiasis is a recognized feature of CNC, but its role in male reproductive dysfunction remains unclear. Recent studies suggest PRKAR1A haploinsufficiency may impair spermatogenesis, leading to reduced fertility. Our findings align with reports of abnormal spermatogenesis in CNC-associated azoospermia. Male infertility may represent an underrecognized feature of CNC. This case highlights the importance of genetic evaluation in infertile men, particularly when testicular microlithiasis and a suggestive family history are present, to enable early recognition of CNC and ensure appropriate surveillance, counseling, and fertility management.