Lifang Dai , Changhong Ding , Xiaojuan Tian , Ming Liu , Yuping Ma , Chunhong Chen , Xiaotun Ren , Hua Li
{"title":"中国儿科患者ATP1A2变异的临床谱","authors":"Lifang Dai , Changhong Ding , Xiaojuan Tian , Ming Liu , Yuping Ma , Chunhong Chen , Xiaotun Ren , Hua Li","doi":"10.1016/j.braindev.2023.04.003","DOIUrl":null,"url":null,"abstract":"<div><h3>Purpose</h3><p>To evaluate the clinical spectrum associated with <em>ATP1A2</em><span> variants in Chinese children with hemiplegia<span>, migraines, encephalopathy or seizures.</span></span></p></div><div><h3>Methods</h3><p>Sixteen children (12 males and 4 females), including ten patients with <em>ATP1A2</em> variants whose cases had been published previously, were identified using next-generation sequencing.</p></div><div><h3>Results</h3><p><span><span><span><span>Fifteen patients had FHM2 (familial hemiplegic migraine type 2), including three who had AHC (alternating hemiplegia of childhood) and one who had drug-resistant </span>focal epilepsy. Thirteen patients had DD (developmental delay). The onset of </span>febrile seizures, which occurred between 5 months and 2 years 5 months (median 1 year 3 months) was earlier than the onset of HM (hemiplegic migraine), which occurred between 1 year 5 months and 13 years (median 3 years 11 months). Disturbance of consciousness subsided first, at 40 h to 9 days (median 4.5 days); hemiplegia and </span>aphasia were resolved slowly, taking 30 min to 6 months (median 17.5 days) for the former and 24 h to over 1 year (median 14.5 days) for the latter. Cranial MRI showed edema in the cerebral hemispheres, mainly the left hemisphereacute attacks. All thirteen FHM2 patients recovered to baseline in 30 min to 6 months. Fifteen patients had between 1 and 7 (median 2) total attacks between the baseline and follow-up timepoints. We report twelve missense variants, including a novel variant </span><em>ATP1A2</em> variant, p.G855E.</p></div><div><h3>Conclusions</h3><p>The known genotypic and phenotypic spectra of Chinese patients with <em>ATP1A2</em>-related disorders were further expanded. Recurrent febrile seizures and DD combined with paroxysmal hemiplegia and encephalopathy should raise the clinical suspicion of FHM2. The avoidance of triggers and thus the prevention of attacks may be the most effective therapy for FHM2.</p></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":null,"pages":null},"PeriodicalIF":1.4000,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The clinical spectrum associated with ATP1A2 variants in Chinese pediatric patients\",\"authors\":\"Lifang Dai , Changhong Ding , Xiaojuan Tian , Ming Liu , Yuping Ma , Chunhong Chen , Xiaotun Ren , Hua Li\",\"doi\":\"10.1016/j.braindev.2023.04.003\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Purpose</h3><p>To evaluate the clinical spectrum associated with <em>ATP1A2</em><span> variants in Chinese children with hemiplegia<span>, migraines, encephalopathy or seizures.</span></span></p></div><div><h3>Methods</h3><p>Sixteen children (12 males and 4 females), including ten patients with <em>ATP1A2</em> variants whose cases had been published previously, were identified using next-generation sequencing.</p></div><div><h3>Results</h3><p><span><span><span><span>Fifteen patients had FHM2 (familial hemiplegic migraine type 2), including three who had AHC (alternating hemiplegia of childhood) and one who had drug-resistant </span>focal epilepsy. Thirteen patients had DD (developmental delay). The onset of </span>febrile seizures, which occurred between 5 months and 2 years 5 months (median 1 year 3 months) was earlier than the onset of HM (hemiplegic migraine), which occurred between 1 year 5 months and 13 years (median 3 years 11 months). Disturbance of consciousness subsided first, at 40 h to 9 days (median 4.5 days); hemiplegia and </span>aphasia were resolved slowly, taking 30 min to 6 months (median 17.5 days) for the former and 24 h to over 1 year (median 14.5 days) for the latter. Cranial MRI showed edema in the cerebral hemispheres, mainly the left hemisphereacute attacks. All thirteen FHM2 patients recovered to baseline in 30 min to 6 months. Fifteen patients had between 1 and 7 (median 2) total attacks between the baseline and follow-up timepoints. We report twelve missense variants, including a novel variant </span><em>ATP1A2</em> variant, p.G855E.</p></div><div><h3>Conclusions</h3><p>The known genotypic and phenotypic spectra of Chinese patients with <em>ATP1A2</em>-related disorders were further expanded. Recurrent febrile seizures and DD combined with paroxysmal hemiplegia and encephalopathy should raise the clinical suspicion of FHM2. The avoidance of triggers and thus the prevention of attacks may be the most effective therapy for FHM2.</p></div>\",\"PeriodicalId\":56137,\"journal\":{\"name\":\"Brain & Development\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.4000,\"publicationDate\":\"2023-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Brain & Development\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0387760423000682\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Brain & Development","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0387760423000682","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
The clinical spectrum associated with ATP1A2 variants in Chinese pediatric patients
Purpose
To evaluate the clinical spectrum associated with ATP1A2 variants in Chinese children with hemiplegia, migraines, encephalopathy or seizures.
Methods
Sixteen children (12 males and 4 females), including ten patients with ATP1A2 variants whose cases had been published previously, were identified using next-generation sequencing.
Results
Fifteen patients had FHM2 (familial hemiplegic migraine type 2), including three who had AHC (alternating hemiplegia of childhood) and one who had drug-resistant focal epilepsy. Thirteen patients had DD (developmental delay). The onset of febrile seizures, which occurred between 5 months and 2 years 5 months (median 1 year 3 months) was earlier than the onset of HM (hemiplegic migraine), which occurred between 1 year 5 months and 13 years (median 3 years 11 months). Disturbance of consciousness subsided first, at 40 h to 9 days (median 4.5 days); hemiplegia and aphasia were resolved slowly, taking 30 min to 6 months (median 17.5 days) for the former and 24 h to over 1 year (median 14.5 days) for the latter. Cranial MRI showed edema in the cerebral hemispheres, mainly the left hemisphereacute attacks. All thirteen FHM2 patients recovered to baseline in 30 min to 6 months. Fifteen patients had between 1 and 7 (median 2) total attacks between the baseline and follow-up timepoints. We report twelve missense variants, including a novel variant ATP1A2 variant, p.G855E.
Conclusions
The known genotypic and phenotypic spectra of Chinese patients with ATP1A2-related disorders were further expanded. Recurrent febrile seizures and DD combined with paroxysmal hemiplegia and encephalopathy should raise the clinical suspicion of FHM2. The avoidance of triggers and thus the prevention of attacks may be the most effective therapy for FHM2.
期刊介绍:
Brain and Development (ISSN 0387-7604) is the Official Journal of the Japanese Society of Child Neurology, and is aimed to promote clinical child neurology and developmental neuroscience.
The journal is devoted to publishing Review Articles, Full Length Original Papers, Case Reports and Letters to the Editor in the field of Child Neurology and related sciences. Proceedings of meetings, and professional announcements will be published at the Editor''s discretion. Letters concerning articles published in Brain and Development and other relevant issues are also welcome.