ESPE Abstracts

Background and Aims: Klinefelter syndrome (KS) is the most common chromosomal abnormality in men, but because of its highly variable phenotype and clinical unawareness, it remains largely under-diagnosed. Cardinal features include tall stature, gynecomastia, hypergonadotropic hypogonadism, azoospermia and infertility. Learning and behavioral problems are also common. Testosterone replacement therapy (TRT) helps to prevent or ameliorate many of the comorbidities associated with KS while improving quality of life. This study aimed to review the data of children and adolescents with KS, including age and presenting symptoms leading to diagnosis, associated comorbidities and clinical and laboratory findings.

Methods: Cross-sectional retrospective study conducted, based on clinical data of patients diagnosed with KS, followed from September 2000 to February 2022 at our Pediatric Endocrinology Unit of a tertiary referral hospital in Portugal.

Results: During the study period, 27 patients were identified. Classical 47,XXY karyotype was detected in 25 (92.6%) subjects and 2 (7.4%) had a karyotype consistent with KS variants. The median maternal age was 35 years. Most of the cases were diagnosed prenatally (n=14, 51.9%). Post-natal diagnosis was made after investigation of development delay (n=5; 38,5%), learning difficulties (n=3, 23,1%), gynecomastia (n=2, 15,4%), scrotal hypospadias (n=1, 7,7%), and/or suggestive phenotype (n=8, 29,6% of them only diagnosed during adolescence). The median age of first visit was eleven years. The most frequent clinical findings were gynecomastia (n=5, 18.5%), cardiac anomalies (n=4, 14,8%), tall stature (n=4, 14,8%), dental abnormalities (n=4, 14,8%), obesity (n=3, 11.1%), asthma (n=3, 11.1%), dyslipidemia (n=2, 7.4%), cryptorchidism (n=2, 7.4%), intellectual development disorders (n=12, 44.4%), hyperactivity and attention deficit disorder (n=11, 40.7%), behavioral and social inadequacies (n=8, 29.6%). None showed thyroid pathology. At the age of 12 years or above, mean follicle stimulating hormone and luteinizing hormone values were 30,4 IU/ml and 10,4 IU/ml, respectively. Puberty onset occurred spontaneously in sixteen cases. Of those who needed TRT (n=19, 70,4%), all had an effective response, 89,5% (n=17) with no side effects. In 88,9%, there was small sized gonads. Spermogram was performed in five patients, which revealed azoospermia in all of them.

Conclusion: KS is an often-missed diagnosis when not detected prenatally. Typical physical features combined with developmental delay should raise clinical suspicion, justifying karyotype analysis, given the high prevalence of this syndrome. TRT is recommended at the beginning of puberty to mitigate long-term consequences of hypogonadism. Further studies are needed to establish optimal TRT, sperm cryopreservation in adolescents and therapeutic targets.