Adrenocorticotropic hormone is recommended worldwide as an initial therapy for infantile spasms. However, infantile spasms in about 50% of children cannot be fully controlled by adrenocorticotropic hormone monotherapy...Adrenocorticotropic hormone is recommended worldwide as an initial therapy for infantile spasms. However, infantile spasms in about 50% of children cannot be fully controlled by adrenocorticotropic hormone monotherapy, seizures recur in 33% of patients who initially respond to adrenocorticotropic hormone monotherapy, and side effects are relatively common during adrenocorticotropic hormone treatment. Topiramate, vitamin B6, and immunoglobulin are effective in some children with infantile spasms. In the present study, we hypothesized that combined therapy with adrenocorticotropic hormone, topiramate, vitamin B6, and immunoglobulin would effectively treat infantile spasms and have mild adverse effects. Thus, 51 children newly diagnosed with West syndrome including infantile spasms were enrolled and underwent polytherapy with the four drugs. Electroencephalographic hypsarrhythmia was significantly improved in a majority of patients, and these patients were seizure-free, had mild side effects, and low recurrence rates. The overall rates of effective treatment and loss of seizures were significantly higher in cryptogenic children compared with symptomatic children. The mean time to loss of seizures in cryptogenic children was significantly shorter than in symptomatic patients. These findings indicate that initial polytherapy with adrenocorticotropic hormone, topiramate, vitamin Be, and immunoglobulin effectively improves the prognosis of infantile spasms, and its effects were superior in cryptogenic children to symptomatic children.展开更多
The autosomal recessive form of primary microcephaly(MCPH)is a rare disorder characterized by microcephaly with variable degree of intellectual disability.WDR62 has been reported as the second causative gene of MCPH2....The autosomal recessive form of primary microcephaly(MCPH)is a rare disorder characterized by microcephaly with variable degree of intellectual disability.WDR62 has been reported as the second causative gene of MCPH2.West syndrome is a severe epilepsy syndrome composed of the triad of spasms,hypsarrhythmia,and mental retardation.There are limited clinical reports regarding WDR62 mutation and West syndrome.Here we report a boy who was identified with WDR62 mutation and was followed up from age 3 months to 5 months and 14 days.He had the first seizure as the classic epileptic spasm at the age of 3 months.Psychomotor retardation was noted before the seizure occurred.The head circumference was 38.5 cm(SD 2.6)when he was 4 months old,no dysmorphic facial features were observed.He couldn’t support his head steadily or turn over.He was able to laugh when tricked by the parents,but couldn’t track the sound and light.At the early stage,the electroencephalogram showed multifocal discharges,which evolved into hypsarrhythmia one month later,and brain MRI showed developmental malformation of cerebral gyrus.Two heterozygous mutations were identified in WDR62 by whole exome sequencing c.1535G>A,p.R512Q and c.2618dupT,p.K874Qfs40.The patient was administrated with oral sodium valproate,nitrazepam,intramuscular adrenocorticotropic hormone for 2 weeks,and followed by prednisone,levetiracetam,topiramate and vigabatrin.However,there was no significant improvement on the seizure control after these treatments.According to the genetic report and clinical manifestation,we speculated that the WDR62 compound heterozygous mutation is responsible for the serious clinical phenotype.展开更多
Background:West syndrome is a devastating disorder characterized by a triad of epileptic spasms,abnormal electroencephalography(EEG),and developmental arrest or psychomotor delay.In addition to early diagnosis,knowing...Background:West syndrome is a devastating disorder characterized by a triad of epileptic spasms,abnormal electroencephalography(EEG),and developmental arrest or psychomotor delay.In addition to early diagnosis,knowing the etiology of the condition is also important for its treatment.Among various etiologies,the genetic factors,especially mutations of ion channel genes,are very common and strongly linked to West syndrome.Case presentation:A boy who had epileptic spasms from the age of 4 months was diagnosed with West syndrome based on the clinical manifestation and EEG results in Shenzhen Children's Hospital in June 2019.Trios whole-exome sequencing(WES)test and protein structural model prediction were performed.We also reviewed the clinical and genetic features of this syndrome and the mechanisms of action of topiramate(TPM)by literature search in databases of Online Mendelian Inheritance in Man,Clinical Genome Resource,PubMed,Chinese National Knowledge Infrastructure and Wanfang database using keywords"KCNA2""West syndrome"and"Topiramate"by December 2020.The relationship between the effect of TPM and the pathogenesis of the KCNA2 variant was also assessed.The WES test revealed c.244C>T/p.Arg82Cys varaint of KCNA2(NM_004974.3)in this patient,and Sanger sequencing identified this was a de novo mutation.As far as we know,this is the first report of the C.244C>T/p.Arg82Cys variant in KCNA2,which was likely a pathogenic mutation.The seizures were successfully controlled for 10 months by TPM after failure of sodium valproate,large doses of vitamin B6,and adrenocorticotropic hormone.We speculate that the therapeutic effect of TPM in this patient is partially due to the inhibition of carbonic anhydrase.Conclusions:Mutations in the KCNA2 gene should be considered for patients with West syndrome.The TPM treatment is probably effective for KCNA2-associated disorders.展开更多
<strong>Background:</strong><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> The epileptic encephalo...<strong>Background:</strong><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> The epileptic encephalopathies collectively</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">exact an immense personal, medical, and financial toll on</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">the affected children, their families, and</span></span></span><span><span><span style="font-family:""> </span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">the healthcare system.</span><b><span style="font-family:Verdana;"> Objective:</span></b><span style="font-family:Verdana;"> This study was aimed to delineate the clinical spectrum of patients with Epileptic encephalopathies (EEs) and classify them under various epileptic syndromes. </span><b><span style="font-family:Verdana;">Methods:</span></b><span style="font-family:Verdana;"> This was a cross-sectional study that was carried out in the department of Neurophysiology of the National Institute of Neurosciences and Hospital, Bangladesh from July 2016 to June 2019.</span></span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">Children with recurrent seizures which w</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">ere </span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">difficult to control and associated with developmental arrest or regression in absence of a progressive brain pathology were considered to be suffering from EE. Children under 12 years of age fulfilling the inclusion criteria were enrolled in the study. These patients were evaluated clinically and Electroencephalography (EEG) was done in all children at presentation. Based on the clinical profile and EEG findings the patients were categorized under various epileptic syndromes according to International League Against Epilepsy (ILAE) classification 2010.</span><b><span style="font-family:Verdana;"> Results:</span></b><span style="font-family:Verdana;"> A total of 1256 children under 12 years of age were referred to the Neurophysiology Department. Among them, 162</span></span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">(12.90%) fulfilled the inclusion criteria. Most of the patients were male (64.2%) and below 1 year (37.7%) of age. The majority (56.8%) were delivered at the hospital and 40.1% had a history of perinatal asphyxia. Development was age-appropriate before the onset of a seizure in 38.9% of cases. Most (53.7%) of the patients had seizure onset within 3 months of age. Categorization of Epileptic syndromes found that majority had West Syndrome (WS)</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">(37.65%) followed by Lennox-Gastaut syndrome (LGS) (22.22%), Otahara syndrome (11.73%), Continuous spike-and-wave during sleep (CSWS) (5.66%), Myoclonic astatic epilepsy (MAE)</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">(4.94%), Early myoclonic encephalopathy (EME) (3.7%), Dravet</span></span></span><span><span><span style="font-family:""> </span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">syndrome (3.7%) and Landau-Kleffner syndrome (LKS) (1.23%). 9.26% of syndromes were unclassified. </span><b><span style="font-family:Verdana;">Conclusion:</span></b><span style="font-family:Verdana;"> EEG was found to be a useful tool in the evaluation of Epileptic encephalopathies. The clinico-electroencephalographic features are age-related. Their recognition and appropriate management are critical.</span></span></span></span>展开更多
Background:Ketogenic diet(KD)therapy is one of the main treatments for drug-resistant epilepsy.However,the KD therapy has been applied in only a small number of infantile spasm cases.In this large multicenter study,we...Background:Ketogenic diet(KD)therapy is one of the main treatments for drug-resistant epilepsy.However,the KD therapy has been applied in only a small number of infantile spasm cases.In this large multicenter study,we investigated the efficacy of KD therapy in the treatment of infantile spasms.Methods:In this retrospective,multicenter cohort study,clinical data from main epilepsy centers were analyzed.Patients were classified into different groups according to age,type of drug and whether glucocorticoid was used before initiation of KD.Results:From October 2014 to March 2020,481 patients(308 males and 173 females)with infantile spasms were treated with the KD therapy.The age of the patients ranged from 2 months to 20 years,with a mean age of 1 year and 10 months.The number of anti-seizure medications(ASMs)used before KD initiation ranged 0-6,with a median of 3.In different time from initiation(1,3,6,and 12 months),the rates of seizure freedom after KD were 6.9,11.6;16.0 and 16.8%,respectively(x^(2)=27.1772,P<0.0001).There was a significant difference in the rate of seizure freedom between 3 months and 1 month(x^(2)=6.5498,P=0.0105)groups,and 6 months and 3 months(x^(2)=3.8478,P=0.0498)groups,but not between 12 months and 6 months(x^(2)=0.1212,P=0.7278)groups.The rates of effectiveness were 44.7;62.8,49.1 and 32.0%(x^(2)=93.2674,P<0.0001),respectively.The retention rates were 94.0,82.5,55.7 and 33.1%(x^(2)=483.7551,P<0.0001),correspondingly.The rate of effectiveness and the retention rate of KD were significantly different among the 1,3,6 and 12 months.KD treatment was the first choice in 25 patients(5.2%),55 patients(11.4%)started KD after the failure of the first ASM,158 patients(32.8%)started KD after the failure of the second ASM,157 patients(32.6%)started KD after the failure of the third drug,and 86 patients(17.9%)started KD after the failure of the fourth and more.The KD effect was not related to the number of ASMs used before KD startup(P>0.05).Two hundred and eighteen patients(45.3%)failed to respond to corticotropin or glucocorticoid before initiation.There was no significant difference in the effectiveness rate at different time points between the group of KD therapy after glucocorticoid failure and the group after non-hormone failure (x^(2)=0.8613,P=0.8348).The rate of adverse events of KD in 1,3,6,and 12 months after KD initiation were 22.3,21.7,16.8 and 6.9%,respectively.The adverse events mainly occurred during the first 3 months of KD,and the main adverse events were gastrointestinal disturbance and constipation.Conclusions:The efficacy of the KD treatment for infantile spasms was not affected by age,medication,and glucocorticoid use before initiation.KD is one of the effective treatments for infantile spasms.展开更多
Introduction:Pathogenic variants inPLOD3,encoding lysyl hydroxylase-3(LH3),can cause a hereditary connective tissue disorder that has rarely been reported.It is a multi-system disease,presenting with craniofacial dysm...Introduction:Pathogenic variants inPLOD3,encoding lysyl hydroxylase-3(LH3),can cause a hereditary connective tissue disorder that has rarely been reported.It is a multi-system disease,presenting with craniofacial dysmorphisms,skeletal and eye manifestations,sensorineural hearing loss,and variable skin manifestations.Severe central nervous system involvement has not been reported.Case presentation:A 10-month-old girl was admitted with development delay and clustered epileptic spasms.Hypertelorism,an upturned nose,and low-set ears were noted in physical examination.Cerebral magnetic resonance imaging showed multiple intracranial malacias and bleeding foci,extensive abnormal signals in the white matter,and obvious brain atrophy,which was consistent with cerebral small vessel disease(SVD).Electroencephalography suggested hypsarrhythmia.The vertebrae were flattened.The distal end of the metacarpal bone in the left hand was irregular.She was diagnosed with West syndrome.Whole-exome sequencing revealed a novel homozygous variant of c.12161218delCTC(p.L406del)inPLOD3,which was found to be inherited from her heterozygous parents.Conclusion:We report a patient with pathogenicPLOD3 mutation who presented with cerebral SVD.This report expands the phenotypic spectrum of LH3 deficiency.展开更多
文摘Adrenocorticotropic hormone is recommended worldwide as an initial therapy for infantile spasms. However, infantile spasms in about 50% of children cannot be fully controlled by adrenocorticotropic hormone monotherapy, seizures recur in 33% of patients who initially respond to adrenocorticotropic hormone monotherapy, and side effects are relatively common during adrenocorticotropic hormone treatment. Topiramate, vitamin B6, and immunoglobulin are effective in some children with infantile spasms. In the present study, we hypothesized that combined therapy with adrenocorticotropic hormone, topiramate, vitamin B6, and immunoglobulin would effectively treat infantile spasms and have mild adverse effects. Thus, 51 children newly diagnosed with West syndrome including infantile spasms were enrolled and underwent polytherapy with the four drugs. Electroencephalographic hypsarrhythmia was significantly improved in a majority of patients, and these patients were seizure-free, had mild side effects, and low recurrence rates. The overall rates of effective treatment and loss of seizures were significantly higher in cryptogenic children compared with symptomatic children. The mean time to loss of seizures in cryptogenic children was significantly shorter than in symptomatic patients. These findings indicate that initial polytherapy with adrenocorticotropic hormone, topiramate, vitamin Be, and immunoglobulin effectively improves the prognosis of infantile spasms, and its effects were superior in cryptogenic children to symptomatic children.
基金Shenzhen Science and Technology PlanningProject(JCYJ20160429180424783)Sanming Project of Medicine inShenzhen(SZSM 201812005).
文摘The autosomal recessive form of primary microcephaly(MCPH)is a rare disorder characterized by microcephaly with variable degree of intellectual disability.WDR62 has been reported as the second causative gene of MCPH2.West syndrome is a severe epilepsy syndrome composed of the triad of spasms,hypsarrhythmia,and mental retardation.There are limited clinical reports regarding WDR62 mutation and West syndrome.Here we report a boy who was identified with WDR62 mutation and was followed up from age 3 months to 5 months and 14 days.He had the first seizure as the classic epileptic spasm at the age of 3 months.Psychomotor retardation was noted before the seizure occurred.The head circumference was 38.5 cm(SD 2.6)when he was 4 months old,no dysmorphic facial features were observed.He couldn’t support his head steadily or turn over.He was able to laugh when tricked by the parents,but couldn’t track the sound and light.At the early stage,the electroencephalogram showed multifocal discharges,which evolved into hypsarrhythmia one month later,and brain MRI showed developmental malformation of cerebral gyrus.Two heterozygous mutations were identified in WDR62 by whole exome sequencing c.1535G>A,p.R512Q and c.2618dupT,p.K874Qfs40.The patient was administrated with oral sodium valproate,nitrazepam,intramuscular adrenocorticotropic hormone for 2 weeks,and followed by prednisone,levetiracetam,topiramate and vigabatrin.However,there was no significant improvement on the seizure control after these treatments.According to the genetic report and clinical manifestation,we speculated that the WDR62 compound heterozygous mutation is responsible for the serious clinical phenotype.
基金This study was sponsored by the Sanming Project of Medicine in Shenzhen(SZSM 201812005)Shenzhen Key Medical Discipline Construction Fund(SZXK033)+1 种基金Epilepsy Research Fund of China Association Against Epilepsy(CU-C-2021-02)Support Project for Clinical Research of Young and Middle-aged Doctors in South of the Ten Ridges Neurology(Z20210308).
文摘Background:West syndrome is a devastating disorder characterized by a triad of epileptic spasms,abnormal electroencephalography(EEG),and developmental arrest or psychomotor delay.In addition to early diagnosis,knowing the etiology of the condition is also important for its treatment.Among various etiologies,the genetic factors,especially mutations of ion channel genes,are very common and strongly linked to West syndrome.Case presentation:A boy who had epileptic spasms from the age of 4 months was diagnosed with West syndrome based on the clinical manifestation and EEG results in Shenzhen Children's Hospital in June 2019.Trios whole-exome sequencing(WES)test and protein structural model prediction were performed.We also reviewed the clinical and genetic features of this syndrome and the mechanisms of action of topiramate(TPM)by literature search in databases of Online Mendelian Inheritance in Man,Clinical Genome Resource,PubMed,Chinese National Knowledge Infrastructure and Wanfang database using keywords"KCNA2""West syndrome"and"Topiramate"by December 2020.The relationship between the effect of TPM and the pathogenesis of the KCNA2 variant was also assessed.The WES test revealed c.244C>T/p.Arg82Cys varaint of KCNA2(NM_004974.3)in this patient,and Sanger sequencing identified this was a de novo mutation.As far as we know,this is the first report of the C.244C>T/p.Arg82Cys variant in KCNA2,which was likely a pathogenic mutation.The seizures were successfully controlled for 10 months by TPM after failure of sodium valproate,large doses of vitamin B6,and adrenocorticotropic hormone.We speculate that the therapeutic effect of TPM in this patient is partially due to the inhibition of carbonic anhydrase.Conclusions:Mutations in the KCNA2 gene should be considered for patients with West syndrome.The TPM treatment is probably effective for KCNA2-associated disorders.
文摘<strong>Background:</strong><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> The epileptic encephalopathies collectively</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">exact an immense personal, medical, and financial toll on</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">the affected children, their families, and</span></span></span><span><span><span style="font-family:""> </span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">the healthcare system.</span><b><span style="font-family:Verdana;"> Objective:</span></b><span style="font-family:Verdana;"> This study was aimed to delineate the clinical spectrum of patients with Epileptic encephalopathies (EEs) and classify them under various epileptic syndromes. </span><b><span style="font-family:Verdana;">Methods:</span></b><span style="font-family:Verdana;"> This was a cross-sectional study that was carried out in the department of Neurophysiology of the National Institute of Neurosciences and Hospital, Bangladesh from July 2016 to June 2019.</span></span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">Children with recurrent seizures which w</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">ere </span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">difficult to control and associated with developmental arrest or regression in absence of a progressive brain pathology were considered to be suffering from EE. Children under 12 years of age fulfilling the inclusion criteria were enrolled in the study. These patients were evaluated clinically and Electroencephalography (EEG) was done in all children at presentation. Based on the clinical profile and EEG findings the patients were categorized under various epileptic syndromes according to International League Against Epilepsy (ILAE) classification 2010.</span><b><span style="font-family:Verdana;"> Results:</span></b><span style="font-family:Verdana;"> A total of 1256 children under 12 years of age were referred to the Neurophysiology Department. Among them, 162</span></span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">(12.90%) fulfilled the inclusion criteria. Most of the patients were male (64.2%) and below 1 year (37.7%) of age. The majority (56.8%) were delivered at the hospital and 40.1% had a history of perinatal asphyxia. Development was age-appropriate before the onset of a seizure in 38.9% of cases. Most (53.7%) of the patients had seizure onset within 3 months of age. Categorization of Epileptic syndromes found that majority had West Syndrome (WS)</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">(37.65%) followed by Lennox-Gastaut syndrome (LGS) (22.22%), Otahara syndrome (11.73%), Continuous spike-and-wave during sleep (CSWS) (5.66%), Myoclonic astatic epilepsy (MAE)</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">(4.94%), Early myoclonic encephalopathy (EME) (3.7%), Dravet</span></span></span><span><span><span style="font-family:""> </span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">syndrome (3.7%) and Landau-Kleffner syndrome (LKS) (1.23%). 9.26% of syndromes were unclassified. </span><b><span style="font-family:Verdana;">Conclusion:</span></b><span style="font-family:Verdana;"> EEG was found to be a useful tool in the evaluation of Epileptic encephalopathies. The clinico-electroencephalographic features are age-related. Their recognition and appropriate management are critical.</span></span></span></span>
基金This study was supported by the Sanming Project of Medicine in Shenzhen(SZSM201812005)Shenzhen Key Medical Discipline Construction Fund(No.SZXK033)Shenzhen Fund for Guangdong Provincial High Level Clinical Key Specialties(No.SZGSPO12).
文摘Background:Ketogenic diet(KD)therapy is one of the main treatments for drug-resistant epilepsy.However,the KD therapy has been applied in only a small number of infantile spasm cases.In this large multicenter study,we investigated the efficacy of KD therapy in the treatment of infantile spasms.Methods:In this retrospective,multicenter cohort study,clinical data from main epilepsy centers were analyzed.Patients were classified into different groups according to age,type of drug and whether glucocorticoid was used before initiation of KD.Results:From October 2014 to March 2020,481 patients(308 males and 173 females)with infantile spasms were treated with the KD therapy.The age of the patients ranged from 2 months to 20 years,with a mean age of 1 year and 10 months.The number of anti-seizure medications(ASMs)used before KD initiation ranged 0-6,with a median of 3.In different time from initiation(1,3,6,and 12 months),the rates of seizure freedom after KD were 6.9,11.6;16.0 and 16.8%,respectively(x^(2)=27.1772,P<0.0001).There was a significant difference in the rate of seizure freedom between 3 months and 1 month(x^(2)=6.5498,P=0.0105)groups,and 6 months and 3 months(x^(2)=3.8478,P=0.0498)groups,but not between 12 months and 6 months(x^(2)=0.1212,P=0.7278)groups.The rates of effectiveness were 44.7;62.8,49.1 and 32.0%(x^(2)=93.2674,P<0.0001),respectively.The retention rates were 94.0,82.5,55.7 and 33.1%(x^(2)=483.7551,P<0.0001),correspondingly.The rate of effectiveness and the retention rate of KD were significantly different among the 1,3,6 and 12 months.KD treatment was the first choice in 25 patients(5.2%),55 patients(11.4%)started KD after the failure of the first ASM,158 patients(32.8%)started KD after the failure of the second ASM,157 patients(32.6%)started KD after the failure of the third drug,and 86 patients(17.9%)started KD after the failure of the fourth and more.The KD effect was not related to the number of ASMs used before KD startup(P>0.05).Two hundred and eighteen patients(45.3%)failed to respond to corticotropin or glucocorticoid before initiation.There was no significant difference in the effectiveness rate at different time points between the group of KD therapy after glucocorticoid failure and the group after non-hormone failure (x^(2)=0.8613,P=0.8348).The rate of adverse events of KD in 1,3,6,and 12 months after KD initiation were 22.3,21.7,16.8 and 6.9%,respectively.The adverse events mainly occurred during the first 3 months of KD,and the main adverse events were gastrointestinal disturbance and constipation.Conclusions:The efficacy of the KD treatment for infantile spasms was not affected by age,medication,and glucocorticoid use before initiation.KD is one of the effective treatments for infantile spasms.
文摘Introduction:Pathogenic variants inPLOD3,encoding lysyl hydroxylase-3(LH3),can cause a hereditary connective tissue disorder that has rarely been reported.It is a multi-system disease,presenting with craniofacial dysmorphisms,skeletal and eye manifestations,sensorineural hearing loss,and variable skin manifestations.Severe central nervous system involvement has not been reported.Case presentation:A 10-month-old girl was admitted with development delay and clustered epileptic spasms.Hypertelorism,an upturned nose,and low-set ears were noted in physical examination.Cerebral magnetic resonance imaging showed multiple intracranial malacias and bleeding foci,extensive abnormal signals in the white matter,and obvious brain atrophy,which was consistent with cerebral small vessel disease(SVD).Electroencephalography suggested hypsarrhythmia.The vertebrae were flattened.The distal end of the metacarpal bone in the left hand was irregular.She was diagnosed with West syndrome.Whole-exome sequencing revealed a novel homozygous variant of c.12161218delCTC(p.L406del)inPLOD3,which was found to be inherited from her heterozygous parents.Conclusion:We report a patient with pathogenicPLOD3 mutation who presented with cerebral SVD.This report expands the phenotypic spectrum of LH3 deficiency.