Ingrid E Scheffer, Sameer Zuberi, Heather C Mefford, Renzo Guerrini, Amy McTague
{"title":"发育性和癫痫性脑病。","authors":"Ingrid E Scheffer, Sameer Zuberi, Heather C Mefford, Renzo Guerrini, Amy McTague","doi":"10.1038/s41572-024-00546-6","DOIUrl":null,"url":null,"abstract":"<p><p>Developmental and epileptic encephalopathies, the most severe group of epilepsies, are characterized by seizures and frequent epileptiform activity associated with developmental slowing or regression. Onset typically occurs in infancy or childhood and includes many well-defined epilepsy syndromes. Patients have wide-ranging comorbidities including intellectual disability, psychiatric features, such as autism spectrum disorder and behavioural problems, movement and musculoskeletal disorders, gastrointestinal and sleep problems, together with an increased mortality rate. Problems change with age and patients require substantial support throughout life, placing a high psychosocial burden on parents, carers and the community. In many patients, the aetiology can be identified, and a genetic cause is found in >50% of patients using next-generation sequencing technologies. More than 900 genes have been identified as monogenic causes of developmental and epileptic encephalopathies and many cell components and processes have been implicated in their pathophysiology, including ion channels and transporters, synaptic proteins, cell signalling and metabolism and epigenetic regulation. Polygenic risk score analyses have shown that common variants also contribute to phenotypic variability. Holistic management, which encompasses antiseizure therapies and care for multimorbidities, is determined both by epilepsy syndrome and aetiology. Identification of the underlying aetiology enables the development of precision medicines to improve the long-term outcome of patients with these devastating diseases.</p>","PeriodicalId":18910,"journal":{"name":"Nature Reviews Disease Primers","volume":null,"pages":null},"PeriodicalIF":76.9000,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Developmental and epileptic encephalopathies.\",\"authors\":\"Ingrid E Scheffer, Sameer Zuberi, Heather C Mefford, Renzo Guerrini, Amy McTague\",\"doi\":\"10.1038/s41572-024-00546-6\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Developmental and epileptic encephalopathies, the most severe group of epilepsies, are characterized by seizures and frequent epileptiform activity associated with developmental slowing or regression. Onset typically occurs in infancy or childhood and includes many well-defined epilepsy syndromes. Patients have wide-ranging comorbidities including intellectual disability, psychiatric features, such as autism spectrum disorder and behavioural problems, movement and musculoskeletal disorders, gastrointestinal and sleep problems, together with an increased mortality rate. Problems change with age and patients require substantial support throughout life, placing a high psychosocial burden on parents, carers and the community. In many patients, the aetiology can be identified, and a genetic cause is found in >50% of patients using next-generation sequencing technologies. More than 900 genes have been identified as monogenic causes of developmental and epileptic encephalopathies and many cell components and processes have been implicated in their pathophysiology, including ion channels and transporters, synaptic proteins, cell signalling and metabolism and epigenetic regulation. Polygenic risk score analyses have shown that common variants also contribute to phenotypic variability. Holistic management, which encompasses antiseizure therapies and care for multimorbidities, is determined both by epilepsy syndrome and aetiology. Identification of the underlying aetiology enables the development of precision medicines to improve the long-term outcome of patients with these devastating diseases.</p>\",\"PeriodicalId\":18910,\"journal\":{\"name\":\"Nature Reviews Disease Primers\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":76.9000,\"publicationDate\":\"2024-09-05\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Nature Reviews Disease Primers\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1038/s41572-024-00546-6\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICINE, GENERAL & INTERNAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature Reviews Disease Primers","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41572-024-00546-6","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, GENERAL & INTERNAL","Score":null,"Total":0}
Developmental and epileptic encephalopathies, the most severe group of epilepsies, are characterized by seizures and frequent epileptiform activity associated with developmental slowing or regression. Onset typically occurs in infancy or childhood and includes many well-defined epilepsy syndromes. Patients have wide-ranging comorbidities including intellectual disability, psychiatric features, such as autism spectrum disorder and behavioural problems, movement and musculoskeletal disorders, gastrointestinal and sleep problems, together with an increased mortality rate. Problems change with age and patients require substantial support throughout life, placing a high psychosocial burden on parents, carers and the community. In many patients, the aetiology can be identified, and a genetic cause is found in >50% of patients using next-generation sequencing technologies. More than 900 genes have been identified as monogenic causes of developmental and epileptic encephalopathies and many cell components and processes have been implicated in their pathophysiology, including ion channels and transporters, synaptic proteins, cell signalling and metabolism and epigenetic regulation. Polygenic risk score analyses have shown that common variants also contribute to phenotypic variability. Holistic management, which encompasses antiseizure therapies and care for multimorbidities, is determined both by epilepsy syndrome and aetiology. Identification of the underlying aetiology enables the development of precision medicines to improve the long-term outcome of patients with these devastating diseases.
期刊介绍:
Nature Reviews Disease Primers, a part of the Nature Reviews journal portfolio, features sections on epidemiology, mechanisms, diagnosis, management, and patient quality of life. The editorial team commissions top researchers — comprising basic scientists and clinical researchers — to write the Primers, which are designed for use by early career researchers, medical students and principal investigators. Each Primer concludes with an Outlook section, highlighting future research directions. Covered medical specialties include Cardiology, Dermatology, Ear, Nose and Throat, Emergency Medicine, Endocrinology, Gastroenterology, Genetic Conditions, Gynaecology and Obstetrics, Hepatology, Haematology, Infectious Diseases, Maxillofacial and Oral Medicine, Nephrology, Neurology, Nutrition, Oncology, Ophthalmology, Orthopaedics, Psychiatry, Respiratory Medicine, Rheumatology, Sleep Medicine, and Urology.