De la Rosa Sebastian Ortiz, Rizzo Valentina, Jauss Robin-Tobias, Bartolomaeus Tobias, Escolar Maria, Bernard Geneviève, Gavrilova Ralitza, Ahrens-Nicklas Rebecca, Lemire Gabrielle, Boycott Kym M, Mercimek-Andrews Saadet, Prontera Paolo, Costa Cinzia, Rakic Bojana, Boerkoel Cornelius F, Huynh Stephanie, Huh Linda, Sherr Elliott, Argilli Emanuela, Ortigoza-Escobar Juan Darío, Casas-Alba Didac, Nunes Tania, Koolen David A, Platzer Konrad, Khinchi Marianne S, Gardella Elena, Fenger Christina D, Møller Rikke S, Bayat Allan
Department of Epilepsy Genetics and Personalized Medicine, Danish Epilepsy Center, Dianalund, Denmark.
Department of Pediatric Neurology, Instituto Roosevelt, Bogotá, Colombia.
Epilepsia. 2025 Jul;66(7):2379-2390. doi: 10.1111/epi.18376. Epub 2025 Mar 21.
Biallelic pathogenic MBOAT7 variants are associated with neurodevelopmental disorders, intellectual disability (ID), epilepsy, and neuropsychiatric disorders such as attention-deficit/hyperactivity disorder and autism spectrum disorders. We aimed to characterize the epilepsy phenotype in a cohort of patients affected by this syndrome.
We describe epilepsy features, electroencephalography, magnetic resonance imaging (MRI) findings, antiseizure treatment response, and neurodevelopment of 15 patients with biallelic MBOAT7 variants.
All 15 patients had ID or developmental delay (DD). Twelve suffered from epilepsy, with mean age at seizure onset of 36 months (range = 2 months-6.5 years) and 10 of 12 showing signs of DD before seizure onset. Patients with epilepsy presented with focal motor seizures with impaired awareness (n = 3), focal tonic-clonic seizures and epileptic spasms (n = 1), focal to bilateral tonic-clonic seizures (n = 1), unknown onset bilateral tonic-clonic seizures (n = 2), myoclonic seizures (n = 4), myoclonic-atonic seizures (n = 1), atonic seizures (n = 1), tonic seizures (n = 1), and myoclonic absences (n = 2). Seizure freedom was achieved in 66.7% (8/12), with variable antiseizure treatment regimes. We reviewed electroencephalograms of the patients with epilepsy. Background activity was normal in 64%, whereas 36% had either a generalized or a focal slowing. Interictal epileptiform discharges (IEDs) were reported in 83%. Generalized spikes/polyspikes were found in 53%, multifocal IEDs in 23%, and parasagittal focal IEDs in 26%. The most frequent abnormal brain MRI findings, reported in 58% of patients, included high-intensity signal in T2 and fluid-attenuated inversion recovery (FLAIR) sequences in dentate nuclei and globus pallidus. Biallelic missense variants seemed to be associated with better cognitive and motor outcomes compared to truncating variants and in-frame deletions.
Biallelic MBOAT7 variants are associated with global developmental impairment in all affected patients and epilepsy in the majority. The seizure semiology is heterogenous. One third of our cohort had persistent seizures despite treatment. The most frequent MRI findings were hyperintensities in T2/FLAIR sequences in dentate nuclei and globus pallidus.
双等位基因致病性MBOAT7变异与神经发育障碍、智力残疾（ID）、癫痫以及神经精神疾病如注意力缺陷多动障碍和自闭症谱系障碍有关。我们旨在描述受该综合征影响的一组患者的癫痫表型。
我们描述了15例双等位基因MBOAT7变异患者的癫痫特征、脑电图、磁共振成像（MRI）结果、抗癫痫治疗反应和神经发育情况。
所有15例患者均有ID或发育迟缓（DD）。12例患有癫痫，癫痫发作的平均年龄为36个月（范围=2个月至6.5岁），12例中有10例在癫痫发作前有DD迹象。癫痫患者出现伴有意识障碍的局灶性运动性发作（n = 3）、局灶性强直阵挛发作和癫痫性痉挛（n = 1）、从局灶性到双侧强直阵挛发作（n = 1）、发作起始不明的双侧强直阵挛发作（n = 2）、肌阵挛发作（n = 4）、肌阵挛失张力发作（n = 1）、失张力发作（n = 1）、强直发作（n = 1）和肌阵挛失神发作（n = 2）。66.7%（8/12）的患者实现了无癫痫发作，采用了不同的抗癫痫治疗方案。我们回顾了癫痫患者的脑电图。64%的患者背景活动正常，而36%的患者有广泛性或局灶性减慢。83%的患者报告有发作间期癫痫样放电（IED）。53%的患者发现广泛性棘波/多棘波，23%的患者发现多灶性IED，26%的患者发现矢状窦旁局灶性IED。58%的患者报告了最常见的异常脑MRI结果，包括齿状核和苍白球T2加权像和液体衰减反转恢复（FLAIR）序列中的高强度信号。与截短变异和框内缺失相比，双等位基因错义变异似乎与更好的认知和运动结果相关。
双等位基因MBOAT7变异与所有受影响患者的全面发育障碍以及大多数患者中的癫痫有关。癫痫发作的症状学是异质性的。我们队列中的三分之一患者尽管接受了治疗仍有持续性癫痫发作。最常见的MRI结果是齿状核和苍白球T2/FLAIR序列中的高信号。
