Comprehensive Evaluation of Clinical, Developmental, Genetic, and Reproductive Characteristics of 133 Patients with...

Klinefelter syndrome, the most common sex chromosome aneuploidy and a major genetic cause of male infertility, is also associated with systemic comorbidities, congenital anomalies, neurodevelopmental impairments, dysmorphic features, and an increased risk of certain malignancies. While the classical form is 47,XXY, mosaicism and higher-grade sex chromosome aneuploidies are also observed. This study aimed to evaluate the clinical and genetic characteristics of patients diagnosed with Klinefelter syndrome over a 25-year period at a single tertiary center and to compare findings across different karyotype groups.

A total of 133 patients diagnosed with Klinefelter syndrome between January 2000 and September 2025 were retrospectively reviewed. Patients were categorized into three groups: 47,XXY; mosaic karyotypes; and higher-grade sex chromosome aneuploidies. Demographic, clinical, and reproductive characteristics were analyzed, and intergroup statistical comparisons were performed.

The majority of patients had a 47,XXY karyotype (87.2%), followed by mosaic forms (6.8%) and higher-grade sex chromosome aneuploidies (6%). Infertility was the most common presenting complaint (62.4%). The predominant clinical findings were hypoplastic or atrophic testes (68.3%), tall stature (15.8%), and gynecomastia (15.8%). Patients with higher-grade sex chromosome aneuploidies were diagnosed at younger ages and exhibited significantly higher rates of congenital anomalies, dysmorphic features, and neurodevelopmental impairment compared with those with the 47,XXY karyotype.

Because most individuals with Klinefelter syndrome are diagnosed in adulthood following infertility evaluation and often display subtle manifestations in childhood, early recognition is essential. Increasing awareness of Klinefelter syndrome is crucial to ensure timely detection and management of associated comorbidities, particularly endocrine disorders.