MBOAT7 encephalopathy: Characterizing the neurology and epileptology
Por:
De la Rosa SO, Rizzo V, Jauss RT, Bartolomaeus T, Escolar M, Bernard G, Gavrilova R, Ahrens-Nicklas R, Lemire G, Boycott KM, Mercimek-Andrews S, Prontera P, Costa C, Rakic B, Boerkoel CF, Huynh S, Huh L, Sherr E, Argilli E, Ortigoza-Escobar JD, Casas-Alba D, Nunes T, Koolen DA, Platzer K, Khinchi MS, Gardella E, Fenger CD, Møller RS and Bayat A
Publicada:
1 jul 2025
Ahead of Print:
1 mar 2025
Resumen:
Objective 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. Methods We describe epilepsy features, electroencephalography, magnetic resonance imaging (MRI) findings, antiseizure treatment response, and neurodevelopment of 15 patients with biallelic MBOAT7 variants. Results 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. Significance 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.
Filiaciones:
De la Rosa SO:
Department of Epilepsy Genetics and Personalized Medicine, Danish Epilepsy Center, Dianalund, Denmark
Department of Pediatric Neurology, Instituto Roosevelt, Bogotá, Colombia
Department of Regional Health Research, University of Southern Denmark, Odense, Denmark
Rizzo V:
Department of Epilepsy Genetics and Personalized Medicine, Danish Epilepsy Center, Dianalund, Denmark
Child Neuropsychiatry, Department of Surgical Sciences, Dentistry, Gynecology, and Pediatrics, University of Verona, Verona, Italy
Jauss RT:
Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany
Bartolomaeus T:
Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany
Escolar M:
Program for the Study of Neurodevelopment in Rare Disorders, University of Pittsburg Medical Center Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
Bernard G:
Departments of Neurology and Neurosurgery, Pediatrics, and Human Genetics, McGill University, Montreal, Quebec, Canada
Child Health and Human Development Program, Research Institute of McGill University Health Centre, Montreal, Quebec, Canada
Gavrilova R:
Department of Clinical Genomics and Neurology, Mayo Clinic, Rochester, Minnesota, USA
Ahrens-Nicklas R:
Division of Human Genetics and Metabolism, Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
Lemire G:
Department of Genetics, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada
Boycott KM:
Department of Genetics, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada
Mercimek-Andrews S:
Department of Medical Genetics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
Prontera P:
Medical Genetics and Rare Disease Unit, Maternal-Infantile Department, S. Maria Della Misericordia Hospital, Perugia, Italy
Costa C:
Neurophysiopathology Unit, Department of Medicine and Surgery, University of Perugia, Perugia, Italy
Rakic B:
Department of Pathology and Laboratory Medicine, Faculty of Medicine, BC Children's Hospital, University of British Columbia, Vancouver, British Columbia, Canada
Boerkoel CF:
Provincial Medical Genetics Program, Department of Medical Genetics, University of British Columbia, Children's and Women's Health Centre of BC, Vancouver, British Columbia, Canada
Huynh S:
Division of Neurology, Department of Pediatrics, Faculty of Medicine, BC Children's Hospital, University of British Columbia, Vancouver, British Columbia, Canada
Huh L:
Division of Neurology, Department of Pediatrics, Faculty of Medicine, BC Children's Hospital, University of British Columbia, Vancouver, British Columbia, Canada
Sherr E:
Department of Neurology and Institute of Human Genetics and Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, California, USA
Argilli E:
Department of Neurology and Institute of Human Genetics and Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, California, USA
Ortigoza-Escobar JD:
Movement Disorders Unit, Pediatric Neurology Department, Institut de Recerca, Hospital San Joan de Déu Barcelona, Reference Center for ERN-RDN, Barcelona, Spain
Casas-Alba D:
Department of Medical Molecular Genetics, Hospital San Joan de Déu Barcelona, Reference Center for ERN-RDN, Barcelona, Spain
Nunes T:
Pediatric Neurology, Pediatric Neurology Department, Institut de Recerca, Hospital San Joan de Déu Barcelona, Reference Center for ERN-RDN, Barcelona, Spain
Pediatric Neurology, Pediatric Department, Hospital General de Vic, Barcelona, Spain
Koolen DA:
Department of Human Genetics, Donders Institute for Brain, Cognition, and Behavior, Radboud University Medical Center, Nijmegen, the Netherlands
Platzer K:
Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany
Khinchi MS:
Department of Pediatrics, Danish Epilepsy Center, Dianalund, Denmark
Gardella E:
Department of Epilepsy Genetics and Personalized Medicine, Danish Epilepsy Center, Dianalund, Denmark
Department of Regional Health Research, University of Southern Denmark, Odense, Denmark
Department of Neurophysiology, Danish Epilepsy Center, member of the European Reference Network EpiCARE, Dianalund, Denmark
Fenger CD:
Department of Regional Health Research, University of Southern Denmark, Odense, Denmark
Amplexa Genetics, Odense, Denmark
Møller RS:
Department of Epilepsy Genetics and Personalized Medicine, Danish Epilepsy Center, Dianalund, Denmark
Department of Regional Health Research, University of Southern Denmark, Odense, Denmark
Bayat A:
Department of Regional Health Research, University of Southern Denmark, Odense, Denmark
Department of Pediatrics, Danish Epilepsy Center, Dianalund, Denmark
Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark
Green Submitted, Green Published, hybrid
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