柯林菲特氏症診斷年齡趨勢：19 年單一中心顯示持續性診斷延遲

楊芯霈、黃志賢、黃逸修、黃奕燊

臺北榮民總醫院 泌尿部

Temporal Trends in the Diagnosis Age of Klinefelter Syndrome and Persistent Delays in Detection over Past Nineteen Years: A Single-Center Study

Hsin-Pei Yang, William J.S. Huang, Eric Yi-Hsiu Huang, I-Shen Huang

Taipei Veterans General Hospital, Department of Urology, Taipei, Taiwan

Purpose: Klinefelter syndrome (KS), the most common sex chromosome aneuploidy (47,XXY), affects approximately 1 in 500–1,000 males and is characterized by infertility, hypogonadism, and multiple metabolic and psychosocial comorbidities. Early identification enables timely testosterone replacement, fertility preservation, and improved long-term health outcomes. However, KS continues to be diagnosed predominantly in adulthood, often after irreversible germ cell loss has occurred. This study aimed to evaluate temporal trends in age at diagnosis and associated clinical characteristics over a 19-year period at a tertiary referral center, with the goal of identifying gaps and opportunities for earlier detection.

Materials and Methods: We conducted a retrospective cohort study of all patients diagnosed with KS via karyotyping at Taipei Veterans General Hospital between January 2007 and October 2025. Extracted variables included age at diagnosis, karyotype subtype, indication for genetic testing, semen analysis results, serum testosterone levels, testicular volume and referring specialty. Temporal trends in diagnosis age were assessed using linear regression, with diagnosis year as the independent variable and age at diagnosis as the dependent variable.

Results: A total of 193 patients were identified, including 169 non-mosaic (including 2 translocations) and 24 mosaic cases. Median age at diagnosis was 35.0 years (IQR, 31–39). Most diagnoses were made by urologists (171, 88.6%), followed by gynecologists (12, 6.2%), pediatricians (7, 3.6%), and endocrinologists (3, 1.6%). Male infertility was the most common indication for genetic testing (164/193, 85.0%), while only 11 (5.7%) presented with testicular atrophy. Among 166 patients with semen analysis, azoospermia was observed in 161/166 patients, (14/16 mosaic, 147/150 non-mosaic). Mean testicular volume was 3.5 ± 1.8 mL. Low serum testosterone (<3 ng/mL) was present in 127/159 adults (79.9%). Linear regression revealed no significant temporal trend in diagnosis age over 19 years (β=-0.0045 years/year, R²=0.0000, p=0.97). The mean age at diagnosis remained stable at approximately 34.5 ± 9.1 years.

Conclusions: Across nearly two decades, the age at KS diagnosis has remained unchanged at the mid-30s, despite advances in medical awareness and increased availability of genetic testing. Most patients continued to present with irreversible azoospermia. Given the high prevalence of testicular atrophy, promoting testicular self-examination and implementing systematic screening programs are crucial for achieving earlier diagnosis and preserving fertility potential in KS patients.