Pub Date : 2023-12-01Epub Date: 2023-01-27DOI: 10.1055/a-2021-0202
Nathalie Alexander, Johannes Cip, Elisabeth Müller, Katrin Lengnick-Lampadius, Philip Julian Broser
In children with therapy refractory epilepsy, the functional disconnection of one hemisphere (hemispherotomy) may be considered as a treatment option. The visual field defects and hand function effects associated with the procedure have been extensively studied. However, the effect of the hemispherotomy on gait pattern has thus far only been analyzed qualitatively, and there is limited quantitative data. At the Children's Hospital, we regularly perform standardized quantitative gait analysis studies and care for children with complex epilepsies. During the standard routine of care for two children with structural therapy refractory epilepsy, gait analysis was performed prior to and after hemispherotomy. Both patients had prenatal ischemic brain lesions, had developed severe epilepsy during the first 3 years of life, and were treated with the hemispherotomy at about 7 years of age. Interestingly, one patient did not show any changes in gait pattern, while for the other patient, differences could be observed by means of three-dimensional gait analysis. However, greater deviations to controls postoperatively may also be related to day-to-day variability.
{"title":"Gait is not Affected by Hemispherotomy-Case Report from Two Children.","authors":"Nathalie Alexander, Johannes Cip, Elisabeth Müller, Katrin Lengnick-Lampadius, Philip Julian Broser","doi":"10.1055/a-2021-0202","DOIUrl":"10.1055/a-2021-0202","url":null,"abstract":"<p><p>In children with therapy refractory epilepsy, the functional disconnection of one hemisphere (hemispherotomy) may be considered as a treatment option. The visual field defects and hand function effects associated with the procedure have been extensively studied. However, the effect of the hemispherotomy on gait pattern has thus far only been analyzed qualitatively, and there is limited quantitative data. At the Children's Hospital, we regularly perform standardized quantitative gait analysis studies and care for children with complex epilepsies. During the standard routine of care for two children with structural therapy refractory epilepsy, gait analysis was performed prior to and after hemispherotomy. Both patients had prenatal ischemic brain lesions, had developed severe epilepsy during the first 3 years of life, and were treated with the hemispherotomy at about 7 years of age. Interestingly, one patient did not show any changes in gait pattern, while for the other patient, differences could be observed by means of three-dimensional gait analysis. However, greater deviations to controls postoperatively may also be related to day-to-day variability.</p>","PeriodicalId":19421,"journal":{"name":"Neuropediatrics","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10847980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-01Epub Date: 2023-08-07DOI: 10.1055/s-0043-1771033
Daniela Formicola, Irina Podda, Marilena Pantaleo, Elena Andreucci, Diego Lopergolo, Sabrina Giglio, Filippo Maria Santorelli, Anna Chilosi
Childhood apraxia of speech (CAS) is a pediatric motor speech disorder. The genetic etiology of this complex neurological condition is not yet well understood, although some genes have been linked to it. We describe the case of a boy with a severe and persistent motor speech disorder, consistent with CAS, and a coexisting language impairment.Whole exome sequencing in our case revealed a de novo and splicing mutation in the CSMD1 gene.
{"title":"Evidence for a Pathogenic Role of CSMD1 in Childhood Apraxia of Speech.","authors":"Daniela Formicola, Irina Podda, Marilena Pantaleo, Elena Andreucci, Diego Lopergolo, Sabrina Giglio, Filippo Maria Santorelli, Anna Chilosi","doi":"10.1055/s-0043-1771033","DOIUrl":"10.1055/s-0043-1771033","url":null,"abstract":"<p><p>Childhood apraxia of speech (CAS) is a pediatric motor speech disorder. The genetic etiology of this complex neurological condition is not yet well understood, although some genes have been linked to it. We describe the case of a boy with a severe and persistent motor speech disorder, consistent with CAS, and a coexisting language impairment.Whole exome sequencing in our case revealed a <i>de novo</i> and splicing mutation in the <i>CSMD1</i> gene.</p>","PeriodicalId":19421,"journal":{"name":"Neuropediatrics","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10325936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-01Epub Date: 2023-10-06DOI: 10.1055/s-0043-1775977
Thea Giacomini, Ramona Cordani, Irene Bagnasco, Fabiana Vercellino, Lucio Giordano, Giuseppe Milito, Giovanni Battista Ferrero, Giorgia Mandrile, Marcello Scala, Mariaclaudia Meli, Raffaele Falsaperla, Gianvittorio Luria, Elisa De Grandis, Edoardo Canale, Elisabetta Amadori, Pasquale Striano, Lino Nobili, Laura Siri
Background: Kleefstra syndrome (KS) or 9q34.3 microdeletion syndrome (OMIM #610253) is a rare genetic condition featuring intellectual disability, hypotonia, and dysmorphic facial features. Autism spectrum disorder, severe language impairment, and sleep disorders have also been described. The syndrome can be either caused by a microdeletion in 9q34.3 or by pathogenic variants in the euchromatin histone methyltransferase 1 gene (EHMT1, *607001). Although epilepsy has been reported in 20 to 30% of subjects, a detailed description of epileptic features and underlying etiology is still lacking. The purpose of this study is to investigate epilepsy features in a cohort of epileptic patients with KS.
Methods: This multicenter study investigated eight patients with KS and epilepsy. Our findings were compared with literature data.
Results: We included five patients with 9q or 9q34.33 deletions, a subject with a complex translocation involving EHMT1, and two with pathogenic EHMT1 variants. All patients presented with moderate to severe developmental delay, language impairment, microcephaly, and infantile hypotonia. Although the epileptic manifestations were heterogeneous, most patients experienced focal seizures. The seizure frequency differs according to the age of epilepsy onset, with patients with early-onset epilepsy (before 36 months of age) presenting more frequent seizures. An overtime reduction in seizure frequency, as well as in antiseizure drug number, was observed in all patients. Developmental delay degree did not correlate with seizure onset and frequency or drug resistance.
Conclusion: Epilepsy is a frequent finding in KS, but the underlying pathogenetic mechanism and specific features remain elusive.
{"title":"Electroclinical Features of Epilepsy in Kleefstra Syndrome.","authors":"Thea Giacomini, Ramona Cordani, Irene Bagnasco, Fabiana Vercellino, Lucio Giordano, Giuseppe Milito, Giovanni Battista Ferrero, Giorgia Mandrile, Marcello Scala, Mariaclaudia Meli, Raffaele Falsaperla, Gianvittorio Luria, Elisa De Grandis, Edoardo Canale, Elisabetta Amadori, Pasquale Striano, Lino Nobili, Laura Siri","doi":"10.1055/s-0043-1775977","DOIUrl":"10.1055/s-0043-1775977","url":null,"abstract":"<p><strong>Background: </strong>Kleefstra syndrome (KS) or 9q34.3 microdeletion syndrome (OMIM #610253) is a rare genetic condition featuring intellectual disability, hypotonia, and dysmorphic facial features. Autism spectrum disorder, severe language impairment, and sleep disorders have also been described. The syndrome can be either caused by a microdeletion in 9q34.3 or by pathogenic variants in the euchromatin histone methyltransferase 1 gene (<i>EHMT1</i>, *607001). Although epilepsy has been reported in 20 to 30% of subjects, a detailed description of epileptic features and underlying etiology is still lacking. The purpose of this study is to investigate epilepsy features in a cohort of epileptic patients with KS.</p><p><strong>Methods: </strong>This multicenter study investigated eight patients with KS and epilepsy. Our findings were compared with literature data.</p><p><strong>Results: </strong>We included five patients with 9q or 9q34.33 deletions, a subject with a complex translocation involving <i>EHMT1</i>, and two with pathogenic <i>EHMT1</i> variants. All patients presented with moderate to severe developmental delay, language impairment, microcephaly, and infantile hypotonia. Although the epileptic manifestations were heterogeneous, most patients experienced focal seizures. The seizure frequency differs according to the age of epilepsy onset, with patients with early-onset epilepsy (before 36 months of age) presenting more frequent seizures. An overtime reduction in seizure frequency, as well as in antiseizure drug number, was observed in all patients. Developmental delay degree did not correlate with seizure onset and frequency or drug resistance.</p><p><strong>Conclusion: </strong>Epilepsy is a frequent finding in KS, but the underlying pathogenetic mechanism and specific features remain elusive.</p>","PeriodicalId":19421,"journal":{"name":"Neuropediatrics","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41130070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-01Epub Date: 2023-08-22DOI: 10.1055/s-0043-1772708
Sara Hommel, T Lücke, A Schmidt-Choudhury
Background: Nutritional management of children and adolescents with severe neurological impairment (SNI) is challenging. A web-based survey was distributed to identify the present situation and the knowledge of the involved medical professionals in Germany.
Methods: The survey was created with LimeSurvey, and access data were distributed by several medical societies. Eighty-three questions covered four topics: "general information," "gastro- and jejunostomy procedure," "handling of gastrostomies and feeding tubes," and "nutritional management and follow-up of children and adolescents with SNI." A descriptive analysis was performed with Microsoft Excel.
Results: A total of 156 participated (65 completed and 91 partially), 27% being pediatric gastroenterologists, 23% pediatric neurologists, and 10% pediatric surgeons. The most common indications for gastrostomy and tube feeding were oropharyngeal dysfunction and failure to thrive. Many patients were still underweight after some months of enteral feeding. The procedure of gastrostomy and handling recommendations varied broadly. Frequently, standard operating procedures (SOPs) and written local guidelines did not exist, and there was a considerable request for training. Only 53% of participants were aware of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition position paper published in 2017, even fewer (38%) followed the guidelines. The recommended measures to assess a nutritional status were often not respected.
Conclusion: Nutritional management of children and adolescents with SNI in Germany is still strongly deficient. Despite the international guideline of 2017, few colleagues are aware of and adhere to the recommendations. This could be improved by interdisciplinary teaching and evaluation of the reasons for noncompliance. The procedure of gastrostomy and the patients' follow-up vary widely. Therefore, modified SOPs should be developed.
{"title":"Nutritional Management in Children and Adolescents with Severe Neurological Impairment-Who Cares? A Web-Based Survey Among Pediatric Specialists in Germany.","authors":"Sara Hommel, T Lücke, A Schmidt-Choudhury","doi":"10.1055/s-0043-1772708","DOIUrl":"10.1055/s-0043-1772708","url":null,"abstract":"<p><strong>Background: </strong>Nutritional management of children and adolescents with severe neurological impairment (SNI) is challenging. A web-based survey was distributed to identify the present situation and the knowledge of the involved medical professionals in Germany.</p><p><strong>Methods: </strong>The survey was created with LimeSurvey, and access data were distributed by several medical societies. Eighty-three questions covered four topics: \"general information,\" \"gastro- and jejunostomy procedure,\" \"handling of gastrostomies and feeding tubes,\" and \"nutritional management and follow-up of children and adolescents with SNI.\" A descriptive analysis was performed with Microsoft Excel.</p><p><strong>Results: </strong>A total of 156 participated (65 completed and 91 partially), 27% being pediatric gastroenterologists, 23% pediatric neurologists, and 10% pediatric surgeons. The most common indications for gastrostomy and tube feeding were oropharyngeal dysfunction and failure to thrive. Many patients were still underweight after some months of enteral feeding. The procedure of gastrostomy and handling recommendations varied broadly. Frequently, standard operating procedures (SOPs) and written local guidelines did not exist, and there was a considerable request for training. Only 53% of participants were aware of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition position paper published in 2017, even fewer (38%) followed the guidelines. The recommended measures to assess a nutritional status were often not respected.</p><p><strong>Conclusion: </strong>Nutritional management of children and adolescents with SNI in Germany is still strongly deficient. Despite the international guideline of 2017, few colleagues are aware of and adhere to the recommendations. This could be improved by interdisciplinary teaching and evaluation of the reasons for noncompliance. The procedure of gastrostomy and the patients' follow-up vary widely. Therefore, modified SOPs should be developed.</p>","PeriodicalId":19421,"journal":{"name":"Neuropediatrics","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10053744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-01Epub Date: 2023-11-13DOI: 10.1055/s-0043-1776112
Kevin Rostasy
{"title":"48th Annual Conference of the German Neuropediatric Society (GNP) and 19th GNP Training Course Academy.","authors":"Kevin Rostasy","doi":"10.1055/s-0043-1776112","DOIUrl":"10.1055/s-0043-1776112","url":null,"abstract":"","PeriodicalId":19421,"journal":{"name":"Neuropediatrics","volume":null,"pages":null},"PeriodicalIF":1.1,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92155669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The neurodevelopmental outcomes in children with tuberous sclerosis complex (TSC) with epileptic spasms remain underdiagnosed and might be responsible for significant morbidity and mortality burdens, even after spasms abate. The study was a cross-sectional study over 18 months at a tertiary care pediatric hospital, involving 30 children with TSC who had epileptic spasms. They were assessed with Diagnostic and Statistical Manual of Mental Disorders-5 criteria for autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), and intellectual disability (ID), and childhood psychopathology measurement schedule (CPMS) for behavioral disorders. The median age at onset of epileptic spasms was 6.5 (1-12) months, and the age at enrolment was 5 (1-15) years. Of 30 children, 2 (6.7%) had only ADHD, 15 (50%) had only ID/GDD (global developmental delay), 4 (13.3%) had ASD and ID/GDD, 3 (10%) had ADHD and ID/GDD, and 6 (20%) had none. The median intelligence quotient/development quotient (IQ/DQ) score was 60.5 (20-105). CPMS assessment revealed significant behavioral abnormalities in almost half the children. Eight (26.7%) patients were completely seizure-free for at least 2 years, 8 (26.7%) had generalized tonic-clonic seizures, 11 (36.6%) had focal epilepsy, and 3 (10%) had evolved into Lennox-Gastaut syndrome. A high proportion of neurodevelopment disorders, including ASD, ADHD, ID/GDD, and behavioral disorders were seen in this pilot study with a small cohort of children with TSC with epileptic spasms.
{"title":"Neurodevelopmental Outcomes of a Cohort of Children with Tuberous Sclerosis Complex with Epileptic Spasms.","authors":"Lokesh Saini, Swetlana Mukherjee, Pradeep Kumar Gunasekaran, Prahbhjot Malhi, Arushi Gahlot Saini, Rajni Sharma, Indar Kumar Sharawat, Renu Suthar, Jitendra Kumar Sahu, Naveen Sankhyan","doi":"10.1055/s-0043-1770937","DOIUrl":"10.1055/s-0043-1770937","url":null,"abstract":"<p><p>The neurodevelopmental outcomes in children with tuberous sclerosis complex (TSC) with epileptic spasms remain underdiagnosed and might be responsible for significant morbidity and mortality burdens, even after spasms abate. The study was a cross-sectional study over 18 months at a tertiary care pediatric hospital, involving 30 children with TSC who had epileptic spasms. They were assessed with Diagnostic and Statistical Manual of Mental Disorders-5 criteria for autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), and intellectual disability (ID), and childhood psychopathology measurement schedule (CPMS) for behavioral disorders. The median age at onset of epileptic spasms was 6.5 (1-12) months, and the age at enrolment was 5 (1-15) years. Of 30 children, 2 (6.7%) had only ADHD, 15 (50%) had only ID/GDD (global developmental delay), 4 (13.3%) had ASD and ID/GDD, 3 (10%) had ADHD and ID/GDD, and 6 (20%) had none. The median intelligence quotient/development quotient (IQ/DQ) score was 60.5 (20-105). CPMS assessment revealed significant behavioral abnormalities in almost half the children. Eight (26.7%) patients were completely seizure-free for at least 2 years, 8 (26.7%) had generalized tonic-clonic seizures, 11 (36.6%) had focal epilepsy, and 3 (10%) had evolved into Lennox-Gastaut syndrome. A high proportion of neurodevelopment disorders, including ASD, ADHD, ID/GDD, and behavioral disorders were seen in this pilot study with a small cohort of children with TSC with epileptic spasms.</p>","PeriodicalId":19421,"journal":{"name":"Neuropediatrics","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10352010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-01Epub Date: 2023-01-05DOI: 10.1055/a-2008-4230
Susanne Oswald, Katja Steinbruecker, Melanie Achleitner, Elisabeth Goeschl, Reginald Bittner, Wolfgang Schmidt, Elke Tiefenthaler, Emma Hammerl, Anna Eisl, Doris Mayr, Johannes Adalbert Mayr, Saskia B Wortmann
Objective: By loading transfer RNAs with their cognate amino acids, aminoacyl-tRNA synthetases (ARS) are essential for protein translation. Both cytosolic ARS1-deficiencies and mitochondrial ARS2 deficiencies can cause severe diseases. Amino acid supplementation has shown to positively influence the clinical course of four individuals with cytosolic ARS1 deficiencies. We hypothesize that this intervention could also benefit individuals with mitochondrial ARS2 deficiencies.
Methods: This study was designed as a N-of-1 trial. Daily oral L-phenylalanine supplementation was used in a 3-year-old girl with FARS2 deficiency. A period without supplementation was implemented to discriminate the effects of treatment from age-related developments and continuing physiotherapy. Treatment effects were measured through a physiotherapeutic testing battery, including movement assessment battery for children, dynamic gait index, gross motor function measure 66, and quality of life questionnaires.
Results: The individual showed clear improvement in all areas tested, especially in gross motor skills, movement abilities, and postural stability. In the period without supplementation, she lost newly acquired motor skills but regained these upon restarting supplementation. No adverse effects and good tolerance of treatment were observed.
Interpretation and conclusion: Our positive results encourage further studies both on L-phenylalanine for other individuals with FARS2 deficiency and the exploration of this treatment rationale for other ARS2 deficiencies. Additionally, treatment costs were relatively low at 1.10 €/day.
{"title":"Treatment of Mitochondrial Phenylalanyl-tRNa-Synthetase Deficiency (FARS2) with Oral Phenylalanine.","authors":"Susanne Oswald, Katja Steinbruecker, Melanie Achleitner, Elisabeth Goeschl, Reginald Bittner, Wolfgang Schmidt, Elke Tiefenthaler, Emma Hammerl, Anna Eisl, Doris Mayr, Johannes Adalbert Mayr, Saskia B Wortmann","doi":"10.1055/a-2008-4230","DOIUrl":"10.1055/a-2008-4230","url":null,"abstract":"<p><strong>Objective: </strong>By loading transfer RNAs with their cognate amino acids, aminoacyl-tRNA synthetases (ARS) are essential for protein translation. Both cytosolic ARS1-deficiencies and mitochondrial ARS2 deficiencies can cause severe diseases. Amino acid supplementation has shown to positively influence the clinical course of four individuals with cytosolic ARS1 deficiencies. We hypothesize that this intervention could also benefit individuals with mitochondrial ARS2 deficiencies.</p><p><strong>Methods: </strong>This study was designed as a N-of-1 trial. Daily oral L-phenylalanine supplementation was used in a 3-year-old girl with FARS2 deficiency. A period without supplementation was implemented to discriminate the effects of treatment from age-related developments and continuing physiotherapy. Treatment effects were measured through a physiotherapeutic testing battery, including movement assessment battery for children, dynamic gait index, gross motor function measure 66, and quality of life questionnaires.</p><p><strong>Results: </strong>The individual showed clear improvement in all areas tested, especially in gross motor skills, movement abilities, and postural stability. In the period without supplementation, she lost newly acquired motor skills but regained these upon restarting supplementation. No adverse effects and good tolerance of treatment were observed.</p><p><strong>Interpretation and conclusion: </strong>Our positive results encourage further studies both on L-phenylalanine for other individuals with FARS2 deficiency and the exploration of this treatment rationale for other ARS2 deficiencies. Additionally, treatment costs were relatively low at 1.10 €/day.</p>","PeriodicalId":19421,"journal":{"name":"Neuropediatrics","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10298576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-01Epub Date: 2023-03-22DOI: 10.1055/a-2060-4576
Raffaele Falsaperla, Roberta Criscione, Carla Cimino, Francesco Pisani, Martino Ruggieri
Background: Autosomal dominant mutations of the KCNQ2 gene can cause two epileptic disorders: benign familial neonatal seizures (BFNS) and developmental epileptic encephalopathy (DEE). This systematic review aims to identify the best reported therapy for these patients, relating to phenotype, neurodevelopmental outcome, and an eventual correlation between phenotype and genotype.
Methods: We searched on PubMed using the search terms "KCNQ2" AND "therapy" and "KCNQ2" AND "treatment"; we found 304 articles. Of these, 29 met our criteria. We collected the data from 194 patients. All 29 articles were retrospective studies.
Results: In all, 104 patients were classified as DEE and 90 as BFNS. After treatment began, 95% of BFNS patients became seizure free, whereas the seizures stopped only in 73% of those with DEE. Phenobarbital and sodium channel blockers were the most used treatment in BFNS. Most of the DEE patients (95%) needed polytherapy for seizure control and even that did not prevent subsequent developmental impairment (77%).Missense mutations were discovered in 96% of DEE patients; these were less common in BFNS (50%), followed by large deletion (16%), truncation (16%), splice donor site (10%), and frameshift (7%).
Conclusion: Phenobarbital or carbamazepine appears to be the most effective antiseizure medication for children with a "benign" variant. On the contrary, polytherapy is often needed for DEE patients, even if it does not seem to improve neurological outcomes. In DEE patients, most mutations were located in S4 and S6 helix, which could serve as a potential target for the development of more specific treatment in the future.
{"title":"KCNQ2-Related Epilepsy: Genotype-Phenotype Relationship with Tailored Antiseizure Medication (ASM)-A Systematic Review.","authors":"Raffaele Falsaperla, Roberta Criscione, Carla Cimino, Francesco Pisani, Martino Ruggieri","doi":"10.1055/a-2060-4576","DOIUrl":"10.1055/a-2060-4576","url":null,"abstract":"<p><strong>Background: </strong>Autosomal dominant mutations of the <i>KCNQ2</i> gene can cause two epileptic disorders: benign familial neonatal seizures (BFNS) and developmental epileptic encephalopathy (DEE). This systematic review aims to identify the best reported therapy for these patients, relating to phenotype, neurodevelopmental outcome, and an eventual correlation between phenotype and genotype.</p><p><strong>Methods: </strong>We searched on PubMed using the search terms \"<i>KCNQ2</i>\" AND \"therapy\" and \"<i>KCNQ2</i>\" AND \"treatment\"; we found 304 articles. Of these, 29 met our criteria. We collected the data from 194 patients. All 29 articles were retrospective studies.</p><p><strong>Results: </strong>In all, 104 patients were classified as DEE and 90 as BFNS. After treatment began, 95% of BFNS patients became seizure free, whereas the seizures stopped only in 73% of those with DEE. Phenobarbital and sodium channel blockers were the most used treatment in BFNS. Most of the DEE patients (95%) needed polytherapy for seizure control and even that did not prevent subsequent developmental impairment (77%).Missense mutations were discovered in 96% of DEE patients; these were less common in BFNS (50%), followed by large deletion (16%), truncation (16%), splice donor site (10%), and frameshift (7%).</p><p><strong>Conclusion: </strong>Phenobarbital or carbamazepine appears to be the most effective antiseizure medication for children with a \"benign\" variant. On the contrary, polytherapy is often needed for DEE patients, even if it does not seem to improve neurological outcomes. In DEE patients, most mutations were located in S4 and S6 helix, which could serve as a potential target for the development of more specific treatment in the future.</p>","PeriodicalId":19421,"journal":{"name":"Neuropediatrics","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10348281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-01Epub Date: 2023-09-18DOI: 10.1055/s-0043-1772667
Ingo Borggraefe, Matias Wagner
The two most common allelic diseases caused by genetic variants in KCNQ2 are either self-limited familiar neonatal epilepsy ( KCNQ2 -SLFNE) or neonatal onset developmental and epileptic encephalopathy ( KCNQ2 -NEO-DEE). 1 In this issue, Falsaperla et al present genotype – phenotype correlation and discuss tailored antiseizure medication (ASM) approaches for KCNQ2 -related epilepsy. The results support previous fi ndings revealing that sodium channel blockers andphenobarbital arethemostcommonlyused and effective ASM for treatment of KCNQ2 -associated conditions. 2 Epilepsy in KCNQ2 -SLFNE is often self-limited. In contrast, patients with KCNQ2 -NEO-DEE are usually severely affected suffering from frequent seizures refractory to ASM polytherapy and present with signi fi cant comorbidities including intellectual impairment and behavioural disturbances emphasizing the need for a precision therapy.
{"title":"Precision Therapy in KCNQ2-Related Epilepsy.","authors":"Ingo Borggraefe, Matias Wagner","doi":"10.1055/s-0043-1772667","DOIUrl":"10.1055/s-0043-1772667","url":null,"abstract":"The two most common allelic diseases caused by genetic variants in KCNQ2 are either self-limited familiar neonatal epilepsy ( KCNQ2 -SLFNE) or neonatal onset developmental and epileptic encephalopathy ( KCNQ2 -NEO-DEE). 1 In this issue, Falsaperla et al present genotype – phenotype correlation and discuss tailored antiseizure medication (ASM) approaches for KCNQ2 -related epilepsy. The results support previous fi ndings revealing that sodium channel blockers andphenobarbital arethemostcommonlyused and effective ASM for treatment of KCNQ2 -associated conditions. 2 Epilepsy in KCNQ2 -SLFNE is often self-limited. In contrast, patients with KCNQ2 -NEO-DEE are usually severely affected suffering from frequent seizures refractory to ASM polytherapy and present with signi fi cant comorbidities including intellectual impairment and behavioural disturbances emphasizing the need for a precision therapy.","PeriodicalId":19421,"journal":{"name":"Neuropediatrics","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10361534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}