Peer-reviewed article

Growing up with Klinefelter syndrome: challenges of care in children and adolescents and patients advocacy.

Mameli C, Street ME, Vernice M, Tarani L, Valsecchi C et al. · 28 Sept 2026

Abstract

Klinefelter syndrome (KS) is a common, yet underdiagnosed sex chromosome aneuploidy characterized by considerable phenotypic variability and multisystem involvement beginning in early life. The increasing use of noninvasive prenatal testing has led to earlier diagnosis, highlighting the need to redefine clinical management across the pediatric age. In this narrative review, pediatric endocrinologists, neuropsychiatrists, psychologists, and genetic experts critically examine current evidence on genetic mechanisms, growth, pubertal development, cardiometabolic risk, and neuropsychological features of KS, and includes a dedicated patient advocacy perspective highlighting family priorities and unmet needs. Emerging evidence indicates that altered body composition, insulin resistance, and neurodevelopmental vulnerabilities may arise in childhood, often preceding overt hypogonadism. Language impairment, executive dysfunction, and social cognitive difficulties represent key determinants of functional outcomes and require early recognition. Early childhood represents a window of opportunity for targeted interventions. A proactive, multidisciplinary, and preventive approach is essential to optimize long-term clinical, cognitive, and social outcomes in individuals with KS.