An Overview of Oxidative Stress in Sex Chromosome Aneuploidies in Pediatric Populations.

Abstract

Background: Oxidative stress, defined as an imbalance between reactive oxygen species and antioxidant defenses, plays a pivotal role in the pathogenesis of sex chromosome aneuploidies (SCAs), such as Turner syndrome (TS) and Klinefelter syndrome (KS). Pediatric patients with SCAs are particularly susceptible due to hormonal deficiencies, metabolic disturbances, and systemic complications.

Methods: A comprehensive literature search was conducted in November 2024 using PubMed, Scopus, and Web of Science. Keywords included "antioxidants", "oxidative stress", "pediatrics", "Turner syndrome", "Klinefelter syndrome", and "sex chromosome aneuploidies". English-language articles were included without publication year restrictions. Relevant data on oxidative stress mechanisms and antioxidant interventions were systematically extracted.

Results: The relationship between oxidative stress and SCAs can be described as bidirectional, where oxidative stress both contributes to and is exacerbated by aneuploidies. TS is marked by estrogen deficiency, cardiovascular anomalies, and metabolic dysfunction, all linked to heightened oxidative stress. KS is associated with hypogonadism, metabolic syndrome, and neurocognitive challenges, further exacerbated by oxidative damage. The aneuploid condition predisposes to increased oxidative stress in other SCAs, including 47,XXX and 47,XYY, as well as in high-grade aneuploidies. Emerging evidence highlights the therapeutic potential of antioxidants, including vitamin C, vitamin E, glutathione precursors, polyphenols, and melatonin. These interventions, when combined with hormonal therapies such as estrogen replacement in TS or testosterone replacement in KS, demonstrate synergistic effects in restoring redox balance and mitigating systemic complications.

Conclusions: Oxidative stress significantly impacts the progression of SCAs in pediatric populations, amplifying risks across metabolic, cardiovascular, and neurocognitive domains. Early, tailored antioxidant strategies, integrated with syndrome-specific hormonal therapies, could reduce long-term complications and improve patient outcomes. Future research should focus on standardizing protocols to optimize these interventions for pediatric patients with SCAs.