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Early onset severe ATP1A2 epileptic encephalopathy: Clinical characteristics and underlying mutations.
Moya-Mendez, Mary E; Mueller, David M; Pratt, Milton; Bonner, Melanie; Elliott, Courtney; Hunanyan, Arsen; Kucera, Gary; Bock, Cheryl; Prange, Lyndsey; Jasien, Joan; Keough, Karen; Shashi, Vandana; McDonald, Marie; Mikati, Mohamad A.
Afiliación
  • Moya-Mendez ME; Department of Pediatrics, Division of Pediatric Neurology and Developmental Medicine, Duke University, Durham, NC, United States.
  • Mueller DM; Center for Genetic Diseases, The Chicago Medical School, Rosalind Franklin University of Medicine and Science, Chicago, IL, United States.
  • Pratt M; Department of Pediatrics, Division of Pediatric Neurology and Developmental Medicine, Duke University, Durham, NC, United States.
  • Bonner M; Department of Psychiatry, Duke University, Durham, NC, United States.
  • Elliott C; Department of Pediatrics, Division of Pediatric Neurology and Developmental Medicine, Duke University, Durham, NC, United States.
  • Hunanyan A; Department of Pediatrics, Division of Pediatric Neurology and Developmental Medicine, Duke University, Durham, NC, United States.
  • Kucera G; Duke Cancer Institute Rodent Cancer Models Shared Resource, Duke University Medical Center, Durham, NC, United States.
  • Bock C; Duke Cancer Institute Rodent Cancer Models Shared Resource, Duke University Medical Center, Durham, NC, United States.
  • Prange L; Department of Pediatrics, Division of Pediatric Neurology and Developmental Medicine, Duke University, Durham, NC, United States.
  • Jasien J; Department of Pediatrics, Division of Pediatric Neurology and Developmental Medicine, Duke University, Durham, NC, United States.
  • Keough K; Dell Medical School at the University of Texas, Austin TX, United States.
  • Shashi V; Dell Medical School at the University of Texas, Austin TX, United States.
  • McDonald M; Dell Medical School at the University of Texas, Austin TX, United States.
  • Mikati MA; Department of Pediatrics, Division of Pediatric Neurology and Developmental Medicine, Duke University, Durham, NC, United States; Department of Neurobiology, Duke University, Durham, NC, United States. Electronic address: Mohamad.Mikati@duke.edu.
Epilepsy Behav ; 116: 107732, 2021 03.
Article en En | MEDLINE | ID: mdl-33493807
BACKGROUND: ATP1A2 mutations cause hemiplegic migraine with or without epilepsy or acute reversible encephalopathy. Typical onset is in adulthood or older childhood without subsequent severe long-term developmental impairments. AIM: We aimed to describe the manifestations of early onset severe ATP1A2-related epileptic encephalopathy and its underlying mutations in a cohort of seven patients. METHODS: A retrospective chart review of a cohort of seven patients was conducted. Response to open-label memantine therapy, used off-label due to its NMDA receptor antagonist effects, was assessed by the Global Rating Scale of Change (GRSC) and Clinical Global Impression Scale of Improvement (CGI-I) methodologies. Molecular modeling was performed using PyMol program. RESULTS: Patients (age 2.5-20 years) had symptom onset at an early age (6 days-1 year). Seizures were either focal or generalized. Common features were: drug resistance, recurrent status epilepticus, etc., severe developmental delay with episodes of acute severe encephalopathy often with headaches, dystonias, hemiplegias, seizures, and developmental regression. All had variants predicted to be disease causing (p.Ile293Met, p.Glu1000Lys, c.1017+5G>A, p.Leu809Arg, and 3 patients with p.Met813Lys). Modeling revealed that mutations interfered with ATP1A2 ion binding and translocation sites. Memantine, given to five, was tolerated in all (mean treatment: 2.3 years, range 6 weeks-4.8 years) with some improvements reported in all five. CONCLUSIONS: Our observations describe a distinctive clinical profile of seven unrelated probands with early onset severe ATP1A2-related epileptic encephalopathy, provide insights into structure-function relationships of ATP1A2 mutations, and support further studies of NMDAR antagonist therapy in ATP1A2-encephalopathy.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Encefalopatías / Epilepsia Tipo de estudio: Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adolescent / Adult / Child / Child, preschool / Humans Idioma: En Revista: Epilepsy Behav Asunto de la revista: CIENCIAS DO COMPORTAMENTO / NEUROLOGIA Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Encefalopatías / Epilepsia Tipo de estudio: Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adolescent / Adult / Child / Child, preschool / Humans Idioma: En Revista: Epilepsy Behav Asunto de la revista: CIENCIAS DO COMPORTAMENTO / NEUROLOGIA Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos