Endocrine Abstracts

Introduction: 48,XYYY is a rare condition where two extra Y chromosomes alter the neurological, skeletal and reproductive development of the affected individual. Clinical features are usually subtle and the diagnosis is not suspected until fertility issues arise. Here, were report an adult patient with 48,XYYY in the Endocrinology Clinic.

Case report: A 24-year-old male was referred to UHL Endocrinology Clinic following infertility evaluation. Blood tests showed primary gonadal failure (raised LH & FSH with low testosterone). Sperm count showed azoospermia. He was referred for microTESE procedure to assist in sperm retrieval. Clinically; tall stature (184cm), high-arched palate, surgically corrected congenital club feet & joint contracture was noted. Ultrasonography showed small volume testes. Despite having normal libido, he described erectile dysfunction and reduced ejaculatory volume. He struggled with anger issues and needed speech therapy as a child. Karyotyping by conventional cryptogenic analysis and Fluorescent In-Situ Hybridisation (FISH) revealed pure 48,XYYY karyotype. One paternal uncle’s family members were taller than average but were not screened for Y aneuploidy.

Discussion: Both 48,XYYY and Klinefelter syndrome (1:500 – 1:1000 males) share similar features of tall stature, joints deformity, long fingers and mental problems. However, 48,XYYY is extremely rare. In fact, only 15 cases have been reported. The few reported 48,XYYY cases share features of skeletal and joints deformity, mental development and reproductive issues. There have been a couple of reports of increased cancer risk with Y chromosome extraploidy but this is difficult to predict due to sparsity of cases. Prenatal diagnosis should be considered for these patients if they become reproductive. We recommend follow up to understand the phenotypic features of this very rare condition.

Learning points: 48,XYYY should be considered as a differential diagnosis when evaluating cases of tall stature, developmental and reproductive issues. Low-threshold to evaluate for malignancy if clinically suspected.