Cerulli Irelli Emanuele, Fanella Martina, Chaumette Boris, Putotto Carolina, Mignot Cyril, Mazzeo Adolfo, Lemke Johannes R, Riva Antonella, Accinni Tommaso, Louveau Cecile, Giovannetti Agnese, Pugnaloni Flaminia, Gavaret Martine, Di Fabio Fabio, Fortunato Francesco, Dorn Thomas, Ferlazzo Edoardo, Gambardella Antonio, Ramantani Georgia, Orlando Biagio, Iftimovici Anton, Operto Francesca F, Pulvirenti Federica, Kluger Gerhard, Caputo Viviana, Striano Pasquale, Di Bonaventura Carlo
Department of Human Neurosciences, Sapienza University of Rome, Rome, Italy.
Fabrizio Spaziani Hospital, Frosinone, Italy.
Epilepsia. 2025 Mar;66(3):859-869. doi: 10.1111/epi.18220. Epub 2024 Dec 24.
This study was undertaken to characterize the clinical and genetic features of patients with 22q11.2 deletion syndrome (22q11.2DS) and generalized epilepsy compared with 22q11.2DS individuals without epilepsy.
This multicenter case-control study included 28 patients with 22q11.2DS-related generalized epilepsy and compared their data with 56 age-matched 22q11.2DS controls without epilepsy. Clinical and electroencephalographic features, neuropsychiatric and systemic comorbidities, family history of epilepsy, and genetic findings were collected.
Generalized tonic-clonic seizures and myoclonic seizures were the most common electroclinical presentations, with a broader range of seizure type combinations also documented. Most patients achieved seizure remission with antiseizure medications, with only 4% exhibiting drug resistance. A higher prevalence of family history of epilepsy was observed among patients with 22q11.2DS-related generalized epilepsy compared to nonepilepsy controls, even when limiting the analysis to patients with known de novo deletions. No differences in deletion size or location were observed between the groups. Multivariable logistic regression analysis identified family history of epilepsy, intellectual disability, and lack of skeletal abnormalities as independent factors associated with generalized epilepsy, whereas a history of psychosis was significant only in univariable analysis.
This study provides a detailed characterization of generalized epilepsy in individuals with 22q11.2DS and highlights specific associated comorbidities. The higher prevalence of family history of epilepsy among cases suggests that genetic factors beyond the 22q11.2 deletion influence the development of the epilepsy phenotype, providing new insights into the genetic underpinnings of phenotypic variability in this syndrome.
本研究旨在描述22q11.2缺失综合征（22q11.2DS）合并全身性癫痫患者的临床和遗传特征，并与无癫痫的22q11.2DS个体进行比较。
这项多中心病例对照研究纳入了28例与22q11.2DS相关的全身性癫痫患者，并将他们的数据与56例年龄匹配的无癫痫的22q11.2DS对照者进行比较。收集了临床和脑电图特征、神经精神和全身合并症、癫痫家族史以及遗传结果。
全身强直阵挛发作和肌阵挛发作是最常见的电临床表型，也记录到了更广泛的发作类型组合。大多数患者通过抗癫痫药物实现了发作缓解，只有4%表现出耐药性。与无癫痫对照组相比，22q11.2DS相关全身性癫痫患者的癫痫家族史患病率更高，即使将分析局限于已知新发缺失的患者。两组之间在缺失大小或位置上未观察到差异。多变量逻辑回归分析确定癫痫家族史、智力残疾和无骨骼异常是与全身性癫痫相关的独立因素，而精神病病史仅在单变量分析中具有显著性。
本研究详细描述了22q11.2DS个体的全身性癫痫特征，并突出了特定的相关合并症。病例组中癫痫家族史的较高患病率表明，22q11.2缺失以外的遗传因素影响癫痫表型的发展，为该综合征表型变异性的遗传基础提供了新的见解。
