Authors :
Presenting Author: Sniya Chirayath, BS – UT Health San Antonio
Aamuktha Pentala, DDS – UT Health San Antonio
Brittany Antopia, MS – UT Health San Antonio
Catherine McCarthy, MS – UT Health San Antonio
Jonathan Gelfond, MD, PhD – UT Health San Antonio
Jannine Cody, Phd – UT Health San Antonio
Kameel KaRKAR, MD – UT Health San Antonio
Rationale:
Previous studies reported seizures and epilepsy in certain chromosome 18 conditions, with most of the reports focusing on trisomy 18, chromosome 18q deletions and mutations of the TCF4 gene on 18q that cause Pitt-Hopkins syndrome. A review of studies of chromosome 18 conditions and epilepsy reported the highest prevalence in trisomy 18 and in chromosome 18q deletions (18q-), with no reported epilepsy in chromosome 18p deletions (18p-)1. However, these publications focused on a subset of the spectrum of chromosome 18 conditions. Furthermore, to date there is not a direct survey of individuals and families of chromosome 18 across a broader spectrum of deletion and duplication conditions. To address this gap, we conducted a focused family survey targeting nine chromosome 18 conditions. Methods:
The cohort consisted of participating families in the Chromosome 18 Clinical Research Center. This includes anyone with any chromosome 18 abnormality focusing on the abnormalities other than trisomy 18. The conditions include deletions (18p-, proximal 18q-, distal 18q- with variable copy number of the TCF4 gene, ring 18) and duplications (trisomy 18p, 18p+, 18q+, tetrasomy 18p)2. Families were invited to complete a REDCap-based seizure survey, regardless of the individual's seizure history. The survey comprised 39 questions covering seizure history, epilepsy diagnosis, seizure semiology, postictal symptoms, comorbidities, medication use and treatment response, and quality of life measures. Prevalence calculations and subgroup comparisons were based on reported counts per condition using Excel software.
Results:
1. Across all groups, reported seizure and epilepsy prevalence exceeded general population estimates for epilepsy (~1%) and seizures (~2–5%). Epilepsy prevalence ranged from 11.1% to 100% (Fig. 1). 2. Drug resistance (i.e., uncontrolled epilepsy despite medication) was typically below 35%, which is lower than the prevalence of drug resistance in epilepsy in general (Fig. 2). 3. Both focal and generalized seizures were reported, as well as convulsive and non-convulsive seizures. 4. Between 20–70% of respondents indicated that seizures negatively impacted quality of life. 5. Cognitive adverse effects attributed to epilepsy were reported in 7 out of 9 groups. Conclusions:
This is the first broad, cross-syndrome survey assessing seizures and epilepsy across multiple chromosome 18 conditions. The results are consistent with increased prevalence of seizures and epilepsy across all conditions. As previously reported, we also found a higher prevalence of epilepsy in 18q- compared to 18p-. While drug resistance was reported in our survey, it appears less common compared to epilepsy cohorts in general; however, the difference may in part be related to community versus clinic-based cohorts. Results reveal a consistently elevated cognitive and psychological burden of seizures and epilepsy. We hope to use data from this survey to ultimately identify epilepsy-important genes on chromosome 18. Family-reported data, though subjective, does offer valuable insights into seizure impact, treatment response, and potential regions of interest on chromosome 18.
Funding: The Chromosome 18 Registry