Authors :
Presenting Author: Quratulain Zulfiqar Ali, MD – Toronto Western Hospital
Caihong Ji, MD – Research Fellow, Neurology, Toronto Western Hospital; Robert De Santis, MD – Neurology – University of Toronto; Farah Qaiser, MSc – Toronto Western Hospital; Tara Sadoway, MSc – Toronto Western Hospital; Danielle Andrade, MD, MSc, FRCPC, CSCN (EEG) – Toronto Western Hospital, University of Toronto
Rationale:
Lennox-Gastaut syndrome (LGS) is an epileptic encephalopathy that manifests in childhood in most cases. The objective of this study is to assess and compare long-term outcomes among distinct etiological groups. Additionally, we conducted an extensive analysis of potential genetic variations in a substantial cohort of LGS patients.
Methods:
A cross-sectional evaluation in cohort of adult LGS between 2019 to 2022, was performed at Toronto Western Hospital’s Adult Genetic Epilepsy (AGE) Clinic. Mean age was 31.60 ± 9.26 (Range from 19 to 55). Seizure outcomes and genetic data were examined. To assess the long-term adaptive behavior of LGS patients, we employed a standardized test based on the Vineland Adaptive Behavior Scales, Version II (VABS-II).
Results:
Forty three adult patients diagnosed with LGS were evaluated in the study:
21 21 (49%) patients had a genetic etiology, 9 (21%) had a structural etiology, and 13 (30%) had an unknown etiology.
No significant differences were observed in long-term seizure outcomes among the three groups.
The ages of seizure onset were lower in the genetic and unknown etiology groups compared to the structural group.
All individuals exhibited varying degrees of adaptive deficiency, ranging from mild to severe.
Whole genome sequencing revealed 15 likely pathogenic or pathogenic genetic variants. These variants included eight single-nucleotide variants (SNV) and seven copy number variants (CNV). Notably, we identified four potentially novel LGS-related variants: HMBS,
KMT2A,
PKP2 and 3q29 duplication. Not all patients with genetic etiology had a gene identified (i.e., some patients with lissencephaly and a few others had malformations of cortical development).
Conclusions:
LGS patients present with persistent unfavorable outcomes regarding seizure control and adaptive behavior throughout their lives, irrespective of the underlying etiology. We uncovered four potentially novel genetic association with LGS, thereby broadening the spectrum of genes/chromosomal abnormalities associated with LGS. However, further investigations are imperative to elucidate the specific relationship between these variants and LGS.
Funding: No funding