2025 Volume 47 Issue 4 Pages 209-214
A rare variant of Klinefelter syndrome, 48XXYY syndrome presents with a wide range of clinical features, including tall stature, intellectual disability, skeletal anomalies, and autism spectrum disorder. We report a male patient with psychomotor developmental delay, progressive genu valgum, dental anomalies, and hypergonadotropic hypogonadism. He was referred to our center at 2 years and 7 months of age, but a definitive diagnosis was not made until he was 16 years old. Although Prader-Willi syndrome was initially suspected, it was ruled out, and he was provisionally diagnosed with cerebral palsy. At 14 years of age, he was re-referred for worsening gait and behavioral issues. Whole-exome sequencing revealed no causative variants, but chromosomal microarray analysis detected gains in the X and Y chromosomes. Conventional G-banding, not performed during the initial workup, later confirmed a 48XXYY karyotype. Laboratory findings supported the diagnosis of hypergonadotropic hypogonadism. This case illustrates the limitations of next-generation sequencing in detecting chromosomal aneuploidies and highlights the diagnostic value of traditional cytogenetic methods. Early identification may enable timely endocrine therapy, educational interventions, and psychosocial support, potentially improving developmental and behavioral outcomes. A stepwise diagnostic approach, beginning with G-banding analysis in patients with unexplained developmental delay and dysmorphic features, remains essential to avoid delayed diagnosis and to optimize patient care.
