Authors :
Presenting Author: Zhixian Yang, PhD – Peking University People's Hospital
Genfu Zhang, PhD Candidate – Peking University People's Hospital
Zongpu Zhou, PhD Candidate – Peking University People's Hospital
Ang Ma, PhD Candidate – Peking University People's Hospital
Jiong Qin, PhD – Peking University People's Hospital
Rationale:
Early-onset absence epilepsy (EOAE) is a rare syndrome resembling childhood absence epilepsy but with earlier onset (≤ 3 or 4 years). Current knowledge is limited by heterogeneous studies and a predominant focus on the genetic etiology of SLC2A1. This study aimed to characterize clinical features, prognostic factors, and genetic architecture in EOAE.Methods:
We enrolled 30 EOAE patients (defined onset age ≤ 4 years) and characterized their demographics, epilepsy phenotypes, and clinical outcomes. Subsequently, patients were stratified by onset age (1–2, 2–3, 3–4 years) and drug resistance International League Against Epilepsy criteria: failure of ≥ 2 ASMs) to enable prognostic comparisons and risk factor analyses.Results:
36.7% (11/30) were male, and 63.3% (19/30) were female, with a median onset age of 33 months. During follow-up, 81.5% (22/27) achieved seizure freedom, with a median seizure-free age of 47 months. Valproic acid (VPA) and lamotrigine were the most commonly used medications, with efficacy rates of 95% and 90.9%, respectively. Developmental delay was observed in 21.4% (6/28), and pathogenic genetic variants (SETD1B, SLC6A1, GABRG2, SCN8A, SCN1A, KMT2E) were detected in 20.0% (6/30). Stratified analysis revealed that the 3-year seizure-free rates were 62.5% for the 1-2 years onset group, 53.8% for the 2-3 years group, and 88.9% for the 3-4 years group, suggesting that earlier onset (1-3 years) may be associated with poorer prognosis. The drug-resistant group exhibited a significantly higher proportion of males (85.7% vs. 21.7%, P=0.004) and a longer median time to seizure freedom (51 months vs. 8 months).Conclusions:
The overall prognosis of EOAE is similar to childhood absence epilepsy, but male gender may be associated with poorer outcomes. This study confirms that onset occurring between the ages of 1 and 3 years is a key predictor of poor prognosis, a conclusion that aligns with observations from prior cohort investigations. VPA has been confirmed as a first-line therapeutic option for EOAE in the Chinese population. Additionally, EOAE exhibits significant genetic heterogeneity. The implicated genes extend beyond the well-known SLC2A1 to include emerging candidates such as SETD1B and SLC6A1. This underscores a more expansive genetic spectrum underlying EOAE than previously appreciated.
Funding:
This work was supported by the National Natural Science Foundation of China (No. 82171436); Beijing Municipal Natural Science Foundation (No. 7252146); Peking University People's Hospital Talent Introduction Start-up Fund (2023-T-02); Peking University People's Hospital R&D Fund Unveiling Project (RDGS2023-10).