To the editor:Myoclonus-dystonia syndrome(MDS)(OMIM15990)is a heritable disorder characterized by early onset subcortical myoclonic jerks and/or less prominent dystonia.This leads to disability and is often refractory...To the editor:Myoclonus-dystonia syndrome(MDS)(OMIM15990)is a heritable disorder characterized by early onset subcortical myoclonic jerks and/or less prominent dystonia.This leads to disability and is often refractory to medical treatment.1 Deep brain stimulation(DBS)for the treatment of refractory MDS has been proven effective in adults for reducing both myoclonic jerks and dystonia.1,2,3 Here,we describe the application of bilateral globus pallidus internus(GPi)DBS in a 5-year-old boy diagnosed with MDS.展开更多
Mitochondrial disease was a clinically and genetically heterogeneous group of diseases, thus the diagnosis was very difficult to clinicians. Our objective was to analyze clinical and genetic characteristics of childre...Mitochondrial disease was a clinically and genetically heterogeneous group of diseases, thus the diagnosis was very difficult to clinicians. Our objective was to analyze clinical and genetic characteristics of children with mitochondrial disease in China. We tested 141 candidate patients who have been suspected of mitochondrial disorders by using targeted next-generation sequencing(NGS), and summarized the clinical and genetic data of gene confirmed cases from Neurology Department, Beijing Children's Hospital, Capital Medical University from October 2012 to January 2015. In our study, 40 cases of gene confirmed mitochondrial disease including eight kinds of mitochondrial disease, among which Leigh syndrome was identified to be the most common type, followed by mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes(MELAS). The age-of-onset varies among mitochondrial disease, but early onset was common. All of 40 cases were gene confirmed, among which 25 cases(62.5%)with mitochondrial DNA(mtDNA) mutation, and 15 cases(37.5%) with nuclear DNA(nDNA) mutation. M.3243A>G(n=7)accounts for a large proportion of mtDNA mutation. The nDNA mutations include SURF1(n=7),PDHA1(n=2),and NDUFV1,NDUFAF6, SUCLA2, SUCLG1, RRM2 B, and C12orf65, respectively.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
Background:Progressive myoclonic epilepsy(PME)is a group of neurodegenerative diseases with genetic heterogeneity and phenotypic similarities,and many cases remain unknown of the genetic causes.This study is aim to su...Background:Progressive myoclonic epilepsy(PME)is a group of neurodegenerative diseases with genetic heterogeneity and phenotypic similarities,and many cases remain unknown of the genetic causes.This study is aim to summarize the clinical features and study the genetic causes of PME patients.Methods:Sanger sequencing of the target gene,Next Generation Sequencing(NGS)panels of epilepsy,trio-based Whole Exome Sequencing(WES)and detection of cytosine-adenine-guanine(CAG)repeat number were used to investigate the genetic causes of PME patients.Results:Thirty-eight children with PME whose seizure onset age ranged from 3 months to 12 years were collected from February 2012 to November 2019 in three hospitals in Beijing,China.The seizure types included myoclonic seizures(n=38),focal seizures(n=19),generalized tonic-clonie seizure(GTCS)(n=13),absence seizures(n=4),atonic seizures(n=3),epileptic spasms(n=2)and tonic seizures(n=1).Twenty-seven cases were sporadic and 11 had family members affected.Established PME-related genes were identified in 30 out of 38(78.9%)patients who had either recessively inherited or de novo heterozygous mutations.Among these 30 cases,there were 12 cases(31.6%)of neuronal ceroid lipofuscinoses(the causing gene contains TPP1,PPT1,CLN5,CLN6 and MFSD8),two cases of sialidosis(the causing gene is NEU1),two cases of neuronopathic Gaucher disease(the causing gene is GBA),one case of spinal muscular atrophy-progressive myoclonic epilepsy(the causing gene is ASAH1),four cases of KCNC1 mutation-related PME,four cases of KCTD7 mutation-related PME,two cases of TBC1D24 mutation-related PME,one case of GOSR2 related PME,and two of dentatorubral-pallidoluysian atrophy(the causing gene is ATN1).In total,13 PME genes were identified in our cohort.The etiology was not clear in eight patients.Conclusion:PME is a group of clinically and genetically heterogeneous diseases.Genetic diagnosis was clear in 78.9%of PME patients.Various of genetic testing methods could increase the rate of genetic diagnosis.Neuronal ceroid lipofuscinoses(NCL)is the most common etiology of PME in children.Nearly one third PME children were diagnosed with NCL.GOSR2 related PME was in our cohort in Asia for the first time.展开更多
基金supported by the China Association Against Epilepsy Scientific Research Project(CU-2022-018).
文摘To the editor:Myoclonus-dystonia syndrome(MDS)(OMIM15990)is a heritable disorder characterized by early onset subcortical myoclonic jerks and/or less prominent dystonia.This leads to disability and is often refractory to medical treatment.1 Deep brain stimulation(DBS)for the treatment of refractory MDS has been proven effective in adults for reducing both myoclonic jerks and dystonia.1,2,3 Here,we describe the application of bilateral globus pallidus internus(GPi)DBS in a 5-year-old boy diagnosed with MDS.
文摘Mitochondrial disease was a clinically and genetically heterogeneous group of diseases, thus the diagnosis was very difficult to clinicians. Our objective was to analyze clinical and genetic characteristics of children with mitochondrial disease in China. We tested 141 candidate patients who have been suspected of mitochondrial disorders by using targeted next-generation sequencing(NGS), and summarized the clinical and genetic data of gene confirmed cases from Neurology Department, Beijing Children's Hospital, Capital Medical University from October 2012 to January 2015. In our study, 40 cases of gene confirmed mitochondrial disease including eight kinds of mitochondrial disease, among which Leigh syndrome was identified to be the most common type, followed by mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes(MELAS). The age-of-onset varies among mitochondrial disease, but early onset was common. All of 40 cases were gene confirmed, among which 25 cases(62.5%)with mitochondrial DNA(mtDNA) mutation, and 15 cases(37.5%) with nuclear DNA(nDNA) mutation. M.3243A>G(n=7)accounts for a large proportion of mtDNA mutation. The nDNA mutations include SURF1(n=7),PDHA1(n=2),and NDUFV1,NDUFAF6, SUCLA2, SUCLG1, RRM2 B, and C12orf65, respectively.
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Key Research Project of the Ministry of Scienceand Technology of China(grant numbers 2016YFC0904400 and2016YFC0904401)The capital health research and development of special(grant number 2016–1-2011).
文摘Background:Progressive myoclonic epilepsy(PME)is a group of neurodegenerative diseases with genetic heterogeneity and phenotypic similarities,and many cases remain unknown of the genetic causes.This study is aim to summarize the clinical features and study the genetic causes of PME patients.Methods:Sanger sequencing of the target gene,Next Generation Sequencing(NGS)panels of epilepsy,trio-based Whole Exome Sequencing(WES)and detection of cytosine-adenine-guanine(CAG)repeat number were used to investigate the genetic causes of PME patients.Results:Thirty-eight children with PME whose seizure onset age ranged from 3 months to 12 years were collected from February 2012 to November 2019 in three hospitals in Beijing,China.The seizure types included myoclonic seizures(n=38),focal seizures(n=19),generalized tonic-clonie seizure(GTCS)(n=13),absence seizures(n=4),atonic seizures(n=3),epileptic spasms(n=2)and tonic seizures(n=1).Twenty-seven cases were sporadic and 11 had family members affected.Established PME-related genes were identified in 30 out of 38(78.9%)patients who had either recessively inherited or de novo heterozygous mutations.Among these 30 cases,there were 12 cases(31.6%)of neuronal ceroid lipofuscinoses(the causing gene contains TPP1,PPT1,CLN5,CLN6 and MFSD8),two cases of sialidosis(the causing gene is NEU1),two cases of neuronopathic Gaucher disease(the causing gene is GBA),one case of spinal muscular atrophy-progressive myoclonic epilepsy(the causing gene is ASAH1),four cases of KCNC1 mutation-related PME,four cases of KCTD7 mutation-related PME,two cases of TBC1D24 mutation-related PME,one case of GOSR2 related PME,and two of dentatorubral-pallidoluysian atrophy(the causing gene is ATN1).In total,13 PME genes were identified in our cohort.The etiology was not clear in eight patients.Conclusion:PME is a group of clinically and genetically heterogeneous diseases.Genetic diagnosis was clear in 78.9%of PME patients.Various of genetic testing methods could increase the rate of genetic diagnosis.Neuronal ceroid lipofuscinoses(NCL)is the most common etiology of PME in children.Nearly one third PME children were diagnosed with NCL.GOSR2 related PME was in our cohort in Asia for the first time.
