Investigating the influence of the reproductive cycle on epilepsy and related behaviours across the life course in SYNGAP1-related disorder.

Women and girls remain underrepresented in neurodevelopmental research, despite recognition that hormonal cycles can significantly influence symptoms such as seizures and emotional regulation. The reproductive cycle is largely unexplored in patients with SYNGAP1 mutations in SYNGAP1-related disorder (SRD), a cause of monogenic neurodevelopmental disorders resulting in severe autism and intellectual disability. Epilepsy is a key comorbidity in SRD, which is present in approximately 93% of patients; absence seizures are the most prevalent epilepsy-type. Puberty and the reproductive cycle can influence seizure occurrence and affect symptoms, such as sensory sensitivities and executive function. It remains unclear how the reproductive cycle influences seizures and behaviours across the life course in SRD. In my PhD, I will study the relationship between the reproductive cycle and SRD symptoms, such as seizures, sleep, and behavioural phenotypes, in rat Syngap knockout models. I will determine if the oestrus cycle is abnormal in Syngap heterozygous females and whether seizures, sleep abnormalities, and spontaneous behaviour phenotypes correlate with the oestrus cycle. Finally, I will modulate the oestrus cycle to determine whether Syngap phenotypes can be rescued. Understanding the relationship between the reproductive cycle and related behavioural phenotypes could lead to refined treatments.