Olson Heather E, Poduri Annapurna, Pearl Phillip L
Division of Epilepsy, Department of Neurology, Boston Children's Hospital, Boston, Massachusetts.
Semin Neurol. 2014 Jul;34(3):266-79. doi: 10.1055/s-0034-1386765. Epub 2014 Sep 5.
Genetic mechanisms explain the pathophysiology of many forms of epilepsy and other paroxysmal disorders, such as alternating hemiplegia of childhood, familial hemiplegic migraine, and paroxysmal dyskinesias. Epilepsy is a key feature of well-defined genetic syndromes including tuberous sclerosis complex, Rett syndrome, Angelman syndrome, and others. There is an increasing number of single-gene causes or susceptibility factors associated with several epilepsy syndromes, including the early-onset epileptic encephalopathies, benign neonatal/infantile seizures, progressive myoclonus epilepsies, genetic generalized and benign focal epilepsies, epileptic aphasias, and familial focal epilepsies. Molecular mechanisms are diverse, and a single gene can be associated with a broad range of phenotypes. Additional features, such as dysmorphisms, head size, movement disorders, and family history may provide clues to a genetic diagnosis. Genetic testing can impact medical care and counseling. We discuss genetic mechanisms of epilepsy and other paroxysmal disorders, tools and indications for genetic testing, known genotype-phenotype associations, the importance of genetic counseling, and a look toward the future of epilepsy genetics.
遗传机制解释了多种形式癫痫及其他发作性疾病的病理生理学,如儿童交替性偏瘫、家族性偏瘫型偏头痛和发作性运动障碍。癫痫是一些明确的遗传综合征的关键特征,包括结节性硬化症复合体、瑞特综合征、天使综合征等。与多种癫痫综合征相关的单基因病因或易感因素越来越多,包括早发性癫痫性脑病、良性新生儿/婴儿惊厥、进行性肌阵挛癫痫、遗传性全身性和良性局灶性癫痫、癫痫性失语症以及家族性局灶性癫痫。分子机制多种多样,单个基因可与广泛的表型相关。其他特征,如畸形、头围大小、运动障碍和家族史,可能为基因诊断提供线索。基因检测会影响医疗护理和咨询。我们讨论癫痫及其他发作性疾病的遗传机制、基因检测的工具和指征、已知的基因型-表型关联、遗传咨询的重要性以及癫痫遗传学的未来展望。