UNLABELLED: Klinefelter syndrome (KS) is the most common sex chromosomal aneuploidy in males (47,XXY karyotype in 80-90% of cases), primarily characterized by hypergonadotropic hypogonadism and infertility. It encompasses a broad phenotypic spectrum, leading to variability in neurocognitive and psychosocial outcomes among affected individuals. Despite the recognized correlation between KS and various neuropsychiatric conditions, studies investigating potential sleep disorders, particularly in pediatric subjects, are lacking. This study aimed to investigate the presence of sleep-related behaviors potentially suggestive of a sleep disorder in a cohort of pediatric patients with KS, in comparison with a group of healthy male age-matched controls. During the period from January to December 2023, a validated sleep questionnaire (Sleep Disturbance Scale for Children: SDSC) was administered to the primary caregivers of 80 children with KS: 40 of preschool age (3-5 years) and 40 of school age (6-16 years). Data were compared with a control group of 180 healthy age-matched male children: 90 of preschool age (3-5 years) and 90 of school age (6-16 years). Among preschoolers, the proportion of subjects with pathological non-restorative sleep T-scores was significantly higher in the KS group compared to controls (p = 0.03). In both KS and control groups, school-aged subjects had higher questionnaire scores compared to preschoolers. The school age KS group had significantly higher mean total T-scores and mean T-scores for disorders of initiating and maintaining sleep (DIMS), disorders of arousal (DA), and disorders of excessive somnolence (DOES) compared to controls (p <
0.01 for all). The KS group also showed significantly higher percentages of children with clinically relevant T-scores for DIMS, DA, DOES, sleep hyperhidrosis, and total T-scores. CONCLUSION: Our study indicates that sleep disorders are more prevalent in children with KS than in the general population, especially in the school age group. Screening for sleep issues in the clinical setting using tools like the SDSC is warranted, and should start from age 6 for children with KS. Further research is needed to better understand the origins of these disturbances, the role of comorbidities, and their long-term effects to improve diagnosis and treatment strategies for these patients. WHAT IS KNOWN: • Neurocognitive and psychosocial disorders can be observed in individuals with KS. • Sleep disorders may be associated with various neuropsychiatric conditions
however, they have not been sufficiently explored in individuals with KS, particularly in pediatric populations. WHAT IS NEW: • Sleep-related problems are more common in children with KS compared to the general population, especially in the school age group with regard to DIMS, DA, and DOES factors. • Starting from 6 years of age, the SDSC might be a promising early diagnostic tool for sleep disorders in children with KS.