What this Trial Is About

Researchers are evaluating the effects of lithium carbonate therapy on behavioral changes in patients with Cornelia de Lange syndrome (CdLS), a rare genetic disorder characterized by intellectual disability, growth delays, distinctive facial features, and multiple malformations. CdLS is caused by mutations affecting the cohesin complex, which is important for gene regulation and central nervous system development. There is currently no approved drug treatment for the cognitive and behavioral symptoms of CdLS, and lithium has shown promise in preclinical models and related conditions by activating the WNT pathway. Participants will receive lithium carbonate capsules at a dose of 10 mg/kg twice daily, with tablets of 150 mg or 300 mg, or a liquid form if swallowing capsules is difficult. The study lasts 52 weeks and includes an initial screening, followed by regular clinical visits for evaluation and monitoring at multiple time points (T1 through T7). Dose adjustments may be made for intolerance, and certain medications are prohibited during the study. After the treatment period, patients benefiting from lithium may continue therapy with ongoing safety monitoring. During the study, participants will undergo cognitive, behavioral, communication, and quality of life assessments using standardized scales at baseline and follow-up visits. Blood tests, ECGs, and biomarker analyses will monitor safety and biological effects, including lithium levels and oxidative stress markers. Caregivers will record medication adherence and report side effects. The primary outcome is behavioral change at 12 months, with secondary outcomes assessing communication, autism symptoms, adaptive functioning, sleep quality, and overall clinical impression.

Cornelia De Lange Syndrome: Assessing Positive Effects of Lithium Treatment