Frasier's syndrome: diagnosis and clinical considerations in adolescence

Abstract

Frasier syndrome is a rare genetic disorder included in sexual development disorders, caused by mutations in the Wilms tumor gene. It is characterized by gonadal dysgenesis in individuals with karyotype 46, XY, female phenotype, progressive nephropathy (usually steroid-resistant nephrotic syndrome) and high risk of gonadal tumors. Case presentation: a 15-year-old female patient with primary amenorrhea, absence of secondary sexual characters and elevated hormone levels. The pelvic ultrasound revealed absence of uterus and atypical gonads. The gonadal biopsy identified disgenetic testicular tissue, and the genetic analysis confirmed a pathogenic mutation in the Wilms tumor gene, establishing the diagnosis of Frasier syndrome. Nephrological follow-up for proteinuria was initiated and prophylactic gonadectomy was scheduled given the high level of gonadal malignancy in adolescence. The diagnosis requires a comprehensive approach that combines clinical, hormonal, imaging, histological and genetic evaluation. Sequencing the WT1 gene is key to confirming differential diagnosis with other sexual development disorders. Prophylactic gonadectomy and renal monitoring are pillars of management, given the progression to renal failure and oncological risk. Frasier syndrome requires a multidisciplinary approach (endocrinology, nephrology, genetics and surgery) to optimize prognosis. Early diagnosis enables timely interventions that improve quality of life and reduce associated morbidity.