Background Alternating hemiplegia of childhood(AHC)is a rare pediatric syndrome characterized by recurring episodes of hemiplegia or quadriplegia,and frequently accompanied by dystonic posturing,choreoathetosis moveme...Background Alternating hemiplegia of childhood(AHC)is a rare pediatric syndrome characterized by recurring episodes of hemiplegia or quadriplegia,and frequently accompanied by dystonic posturing,choreoathetosis movements,anomalous ocular motions,and a gradual deterioration in cognitive function.The principal etiology of this disorder is traced back to mutations in the ATP1A3 gene.Case presentation Here,we report a 16-year-old girl with recurrent hemiplegia since her infancy.This patient has experienced paroxysmal limb weakness and aphasia for over 15 years,and has kept seeking medical attention but without receiving effective treatment.A misdiagnosis of hysteria persisted for over 4 years until the patient’s admission to our hospital.Whole-exome sequencing identified a known pathogenic heterozygous c.2270T>C(p.Leu757Pro)mutation in her ATP1A3 gene.Notably,her clinical manifestations,including pathological emotional responses and autonomic dysfunction,differed from the established profile associated with the same ATP1A3 mutation,which typically present with intellectual disability,a rostrocaudal symptom gradient,choreoathetosis,and dysarthria.The patient was finally diagnosed with AHC and treated with flunarizine thus significantly ameliorated hemiplegic episodes.Conclusions This case enhances our understanding of the intricate clinical manifestations of AHC,which require careful differentiation from various diseases such as epilepsy,hysteria,and paroxysmal dyskinesias.In the diagnosis of patients presenting with suspected symptoms,adhering to a systematic approach for localizing and diagnosing neurological disorders is crucial to prevent misdiagnosis and inappropriate treatments.Additionally,when AHC is suspected in a patient,genetic testing should be considered as part of the diagnostic approach.展开更多
Importance:The phenotypes of ATP1A3 gene mutations are diverse.Relapsing encephalopathy with cerebellar ataxia and fever-induced paroxysmal weakness and encephalopathy(FIPWE)are considered non-classical phenotypes cau...Importance:The phenotypes of ATP1A3 gene mutations are diverse.Relapsing encephalopathy with cerebellar ataxia and fever-induced paroxysmal weakness and encephalopathy(FIPWE)are considered non-classical phenotypes caused by p.Arg756 mutations of ATP1A3.Objective:To summarize the clinical manifestations,treatment,and followup of Chinese patients with p.Arg756 mutations of ATP1A3.Methods:We analyzed the clinical features,treatment,and genotypes of eight children with p.Arg756 mutations of ATP1A3 who were treated in Beijing Children’s Hospital from January 2014 to December 2019.Results:Eight patients(six boys and two girls)were included;seven had been misdiagnosed with encephalitis.The age of onset ranged from 0.8 to 4.5 years.All patients had encephalopathy and had at least one episode of FIPWE.Cerebellar ataxia was present in nine episodes.Reversible splenial lesions of the corpus callosum were found in two patients in the acute phase.Three types of heterozygous ATP1A3 mutations were found:c.2267G>T(p.R756L)(patient 3[P3]),c.2266C>T(p.R756C)(P2 and P4),and c.2267G>A(p.R756H)(P1,P5,P6,P7,and P8).Six mutations were de novo;two mutations were inherited.Both patients with p.R756C and one patient(P7)with p.R756H had four episodes of severe ataxia as the main manifestations.However,in the other three episodes,limb weakness was more prominent than ataxia.P5 with p.R756H exhibited overlap with FIPWE and rapid-onset dystonia-parkinsonism.Interpretation:Acute encephalopathy followed by febrile disease was characteristic of the disease in patients with p.Arg756 mutations of ATP1A3.However,the weakness and ataxia were variable.Phenotypic crossover and overlap were observed among these patients.展开更多
Alternating hemiplegia of childhood is a rare neurodevelopmental disorder.Most cases are reported as sporadic disorder due to de novo variants,and few with family members involved.Two boys were hospitalized due to epi...Alternating hemiplegia of childhood is a rare neurodevelopmental disorder.Most cases are reported as sporadic disorder due to de novo variants,and few with family members involved.Two boys were hospitalized due to epileptic seizures occurred initially at age of six to seven months.During the course of the disease,there were repeated episodes of paroxysmal weakness or paralysis affecting one side of the body.Genetic testing showed that both patients carried heterozygous missense mutations in the ATP1A3 gene(OMIM:614820):c.3025(exon 22)A>G(p.K1009E)and c.2443(exon 18)G>A(p.E815K).Flunarizine can significantly improve the paroxysmal motor symptoms of pediatric patients with alternating hemiplegia.展开更多
儿童交替性偏瘫(Alternating hemiplegia of childhood,AHC)是一种罕见的神经发育障碍疾病,主要表现以反复发作的肌肉无力或瘫痪为特征,通常影响一侧躯体。其中,大多数病例是散发的,少数病例有家族史。现报道1例早期被误诊为癫痫的儿童...儿童交替性偏瘫(Alternating hemiplegia of childhood,AHC)是一种罕见的神经发育障碍疾病,主要表现以反复发作的肌肉无力或瘫痪为特征,通常影响一侧躯体。其中,大多数病例是散发的,少数病例有家族史。现报道1例早期被误诊为癫痫的儿童交替性偏瘫患者。1病例资料患儿,女,1岁,因“间断抽搐1年余,双眼向左侧凝视,肢体交替性偏瘫”于2022年7月23日入住我院儿科。展开更多
文摘Background Alternating hemiplegia of childhood(AHC)is a rare pediatric syndrome characterized by recurring episodes of hemiplegia or quadriplegia,and frequently accompanied by dystonic posturing,choreoathetosis movements,anomalous ocular motions,and a gradual deterioration in cognitive function.The principal etiology of this disorder is traced back to mutations in the ATP1A3 gene.Case presentation Here,we report a 16-year-old girl with recurrent hemiplegia since her infancy.This patient has experienced paroxysmal limb weakness and aphasia for over 15 years,and has kept seeking medical attention but without receiving effective treatment.A misdiagnosis of hysteria persisted for over 4 years until the patient’s admission to our hospital.Whole-exome sequencing identified a known pathogenic heterozygous c.2270T>C(p.Leu757Pro)mutation in her ATP1A3 gene.Notably,her clinical manifestations,including pathological emotional responses and autonomic dysfunction,differed from the established profile associated with the same ATP1A3 mutation,which typically present with intellectual disability,a rostrocaudal symptom gradient,choreoathetosis,and dysarthria.The patient was finally diagnosed with AHC and treated with flunarizine thus significantly ameliorated hemiplegic episodes.Conclusions This case enhances our understanding of the intricate clinical manifestations of AHC,which require careful differentiation from various diseases such as epilepsy,hysteria,and paroxysmal dyskinesias.In the diagnosis of patients presenting with suspected symptoms,adhering to a systematic approach for localizing and diagnosing neurological disorders is crucial to prevent misdiagnosis and inappropriate treatments.Additionally,when AHC is suspected in a patient,genetic testing should be considered as part of the diagnostic approach.
文摘Importance:The phenotypes of ATP1A3 gene mutations are diverse.Relapsing encephalopathy with cerebellar ataxia and fever-induced paroxysmal weakness and encephalopathy(FIPWE)are considered non-classical phenotypes caused by p.Arg756 mutations of ATP1A3.Objective:To summarize the clinical manifestations,treatment,and followup of Chinese patients with p.Arg756 mutations of ATP1A3.Methods:We analyzed the clinical features,treatment,and genotypes of eight children with p.Arg756 mutations of ATP1A3 who were treated in Beijing Children’s Hospital from January 2014 to December 2019.Results:Eight patients(six boys and two girls)were included;seven had been misdiagnosed with encephalitis.The age of onset ranged from 0.8 to 4.5 years.All patients had encephalopathy and had at least one episode of FIPWE.Cerebellar ataxia was present in nine episodes.Reversible splenial lesions of the corpus callosum were found in two patients in the acute phase.Three types of heterozygous ATP1A3 mutations were found:c.2267G>T(p.R756L)(patient 3[P3]),c.2266C>T(p.R756C)(P2 and P4),and c.2267G>A(p.R756H)(P1,P5,P6,P7,and P8).Six mutations were de novo;two mutations were inherited.Both patients with p.R756C and one patient(P7)with p.R756H had four episodes of severe ataxia as the main manifestations.However,in the other three episodes,limb weakness was more prominent than ataxia.P5 with p.R756H exhibited overlap with FIPWE and rapid-onset dystonia-parkinsonism.Interpretation:Acute encephalopathy followed by febrile disease was characteristic of the disease in patients with p.Arg756 mutations of ATP1A3.However,the weakness and ataxia were variable.Phenotypic crossover and overlap were observed among these patients.
基金Research Fund of Anhui Medical University(Grant Number:2019xkj176).
文摘Alternating hemiplegia of childhood is a rare neurodevelopmental disorder.Most cases are reported as sporadic disorder due to de novo variants,and few with family members involved.Two boys were hospitalized due to epileptic seizures occurred initially at age of six to seven months.During the course of the disease,there were repeated episodes of paroxysmal weakness or paralysis affecting one side of the body.Genetic testing showed that both patients carried heterozygous missense mutations in the ATP1A3 gene(OMIM:614820):c.3025(exon 22)A>G(p.K1009E)and c.2443(exon 18)G>A(p.E815K).Flunarizine can significantly improve the paroxysmal motor symptoms of pediatric patients with alternating hemiplegia.
文摘儿童交替性偏瘫(Alternating hemiplegia of childhood,AHC)是一种罕见的神经发育障碍疾病,主要表现以反复发作的肌肉无力或瘫痪为特征,通常影响一侧躯体。其中,大多数病例是散发的,少数病例有家族史。现报道1例早期被误诊为癫痫的儿童交替性偏瘫患者。1病例资料患儿,女,1岁,因“间断抽搐1年余,双眼向左侧凝视,肢体交替性偏瘫”于2022年7月23日入住我院儿科。
