Daniel Natera-de Benito , Alessia Pugliese , Kiran Polavarapu , Velina Guergueltcheva , Ivailo Tournev , Albena Todorova , Joana Afonso Ribeiro , Daniel M. Fernández-Mayoralas , Carlos Ortez , Loreto Martorell , Berta Estévez-Arias , Leslie Matalonga , Steven Laurie , Cristina Jou , Jarred Lau , Rachel Thompson , Xinming Shen , Andrew G. Engel , Andres Nascimento , Hanns Lochmüller , Duygu Selcen
{"title":"增进对 VAMP1 相关先天性肌无力综合征的了解:表型见解、对 3,4-二氨基吡啶的良好反应以及五个新病例的临床特征描述","authors":"Daniel Natera-de Benito , Alessia Pugliese , Kiran Polavarapu , Velina Guergueltcheva , Ivailo Tournev , Albena Todorova , Joana Afonso Ribeiro , Daniel M. Fernández-Mayoralas , Carlos Ortez , Loreto Martorell , Berta Estévez-Arias , Leslie Matalonga , Steven Laurie , Cristina Jou , Jarred Lau , Rachel Thompson , Xinming Shen , Andrew G. Engel , Andres Nascimento , Hanns Lochmüller , Duygu Selcen","doi":"10.1016/j.pediatrneurol.2024.04.027","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>Congenital myasthenic syndromes (CMS) are a group of inherited neuromuscular junction (NMJ) disorders arising from gene variants encoding diverse NMJ proteins. Recently, the <em>VAMP1</em> gene, responsible for encoding the vesicle-associated membrane protein 1 (VAMP1), has been associated with CMS.</p></div><div><h3>Methods</h3><p>This study presents a characterization of five new individuals with VAMP1-related CMS, providing insights into the phenotype.</p></div><div><h3>Results</h3><p>The individuals with VAMP1-related CMS exhibited early disease onset, presenting symptoms prenatally or during the neonatal period, alongside severe respiratory involvement and feeding difficulties. Generalized weakness at birth was a common feature, and none of the individuals achieved independent walking ability. Notably, all cases exhibited scoliosis. The clinical course remained stable, without typical exacerbations seen in other CMS types. The response to anticholinesterase inhibitors and salbutamol was only partial, but the addition of 3,4-diaminopyridine (3,4-DAP) led to significant and substantial improvements, suggesting therapeutic benefits of 3,4-DAP for managing VAMP1-related CMS symptoms. Noteworthy is the identification of the <em>VAMP1</em> (NM_014231.5): c.340delA; p.Ile114SerfsTer72 as a founder variant in the Iberian Peninsula and Latin America.</p></div><div><h3>Conclusions</h3><p>This study contributes valuable insights into VAMP1-related CMS, emphasizing their early onset, arthrogryposis, facial and generalized weakness, respiratory involvement, and feeding difficulties. Furthermore, the potential efficacy of 3,4-DAP as a useful therapeutic option warrants further exploration. The findings have implications for clinical management and genetic counseling in affected individuals. Additional research is necessary to elucidate the long-term outcomes of VAMP1-related CMS.</p></div>","PeriodicalId":19956,"journal":{"name":"Pediatric neurology","volume":null,"pages":null},"PeriodicalIF":3.2000,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Advancing the Understanding of Vesicle-Associated Membrane Protein 1-Related Congenital Myasthenic Syndrome: Phenotypic Insights, Favorable Response to 3,4-Diaminopyridine, and Clinical Characterization of Five New Cases\",\"authors\":\"Daniel Natera-de Benito , Alessia Pugliese , Kiran Polavarapu , Velina Guergueltcheva , Ivailo Tournev , Albena Todorova , Joana Afonso Ribeiro , Daniel M. Fernández-Mayoralas , Carlos Ortez , Loreto Martorell , Berta Estévez-Arias , Leslie Matalonga , Steven Laurie , Cristina Jou , Jarred Lau , Rachel Thompson , Xinming Shen , Andrew G. Engel , Andres Nascimento , Hanns Lochmüller , Duygu Selcen\",\"doi\":\"10.1016/j.pediatrneurol.2024.04.027\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><p>Congenital myasthenic syndromes (CMS) are a group of inherited neuromuscular junction (NMJ) disorders arising from gene variants encoding diverse NMJ proteins. Recently, the <em>VAMP1</em> gene, responsible for encoding the vesicle-associated membrane protein 1 (VAMP1), has been associated with CMS.</p></div><div><h3>Methods</h3><p>This study presents a characterization of five new individuals with VAMP1-related CMS, providing insights into the phenotype.</p></div><div><h3>Results</h3><p>The individuals with VAMP1-related CMS exhibited early disease onset, presenting symptoms prenatally or during the neonatal period, alongside severe respiratory involvement and feeding difficulties. Generalized weakness at birth was a common feature, and none of the individuals achieved independent walking ability. Notably, all cases exhibited scoliosis. The clinical course remained stable, without typical exacerbations seen in other CMS types. The response to anticholinesterase inhibitors and salbutamol was only partial, but the addition of 3,4-diaminopyridine (3,4-DAP) led to significant and substantial improvements, suggesting therapeutic benefits of 3,4-DAP for managing VAMP1-related CMS symptoms. Noteworthy is the identification of the <em>VAMP1</em> (NM_014231.5): c.340delA; p.Ile114SerfsTer72 as a founder variant in the Iberian Peninsula and Latin America.</p></div><div><h3>Conclusions</h3><p>This study contributes valuable insights into VAMP1-related CMS, emphasizing their early onset, arthrogryposis, facial and generalized weakness, respiratory involvement, and feeding difficulties. Furthermore, the potential efficacy of 3,4-DAP as a useful therapeutic option warrants further exploration. The findings have implications for clinical management and genetic counseling in affected individuals. Additional research is necessary to elucidate the long-term outcomes of VAMP1-related CMS.</p></div>\",\"PeriodicalId\":19956,\"journal\":{\"name\":\"Pediatric neurology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.2000,\"publicationDate\":\"2024-05-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pediatric neurology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0887899424001565\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pediatric neurology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0887899424001565","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Advancing the Understanding of Vesicle-Associated Membrane Protein 1-Related Congenital Myasthenic Syndrome: Phenotypic Insights, Favorable Response to 3,4-Diaminopyridine, and Clinical Characterization of Five New Cases
Background
Congenital myasthenic syndromes (CMS) are a group of inherited neuromuscular junction (NMJ) disorders arising from gene variants encoding diverse NMJ proteins. Recently, the VAMP1 gene, responsible for encoding the vesicle-associated membrane protein 1 (VAMP1), has been associated with CMS.
Methods
This study presents a characterization of five new individuals with VAMP1-related CMS, providing insights into the phenotype.
Results
The individuals with VAMP1-related CMS exhibited early disease onset, presenting symptoms prenatally or during the neonatal period, alongside severe respiratory involvement and feeding difficulties. Generalized weakness at birth was a common feature, and none of the individuals achieved independent walking ability. Notably, all cases exhibited scoliosis. The clinical course remained stable, without typical exacerbations seen in other CMS types. The response to anticholinesterase inhibitors and salbutamol was only partial, but the addition of 3,4-diaminopyridine (3,4-DAP) led to significant and substantial improvements, suggesting therapeutic benefits of 3,4-DAP for managing VAMP1-related CMS symptoms. Noteworthy is the identification of the VAMP1 (NM_014231.5): c.340delA; p.Ile114SerfsTer72 as a founder variant in the Iberian Peninsula and Latin America.
Conclusions
This study contributes valuable insights into VAMP1-related CMS, emphasizing their early onset, arthrogryposis, facial and generalized weakness, respiratory involvement, and feeding difficulties. Furthermore, the potential efficacy of 3,4-DAP as a useful therapeutic option warrants further exploration. The findings have implications for clinical management and genetic counseling in affected individuals. Additional research is necessary to elucidate the long-term outcomes of VAMP1-related CMS.
期刊介绍:
Pediatric Neurology publishes timely peer-reviewed clinical and research articles covering all aspects of the developing nervous system.
Pediatric Neurology features up-to-the-minute publication of the latest advances in the diagnosis, management, and treatment of pediatric neurologic disorders. The journal''s editor, E. Steve Roach, in conjunction with the team of Associate Editors, heads an internationally recognized editorial board, ensuring the most authoritative and extensive coverage of the field. Among the topics covered are: epilepsy, mitochondrial diseases, congenital malformations, chromosomopathies, peripheral neuropathies, perinatal and childhood stroke, cerebral palsy, as well as other diseases affecting the developing nervous system.