Anja Troha Gergeli1, David Neubauer2, Tanja Golli2, Tita Butenko1, Tanja Loboda1, Aleš Maver3, Damjan Osredkar4. 1. Department of Child, Adolescent and Developmental Neurology, University Children's Hospital, University Medical Centre Ljubljana, Slovenia. 2. Department of Child, Adolescent and Developmental Neurology, University Children's Hospital, University Medical Centre Ljubljana, Slovenia; Faculty of Medicine, University of Ljubljana, Slovenia. 3. Clinical Institute of Medical Genetics, University Medical Centre Ljubljana, Slovenia. 4. Department of Child, Adolescent and Developmental Neurology, University Children's Hospital, University Medical Centre Ljubljana, Slovenia; Faculty of Medicine, University of Ljubljana, Slovenia. Electronic address: damjan.osredkar@kclj.si.
Abstract
AIM: Congenital myasthenic syndromes (CMS) are rare, genetically and phenotypically diverse disorders of neuromuscular transmission. Data on prevalence among children are scarce. Whole exome sequencing facilitated discovery of novel CMS mutations and enabled targeted treatment. Our aim was to identify the prevalence, genetic subtypes and clinical characteristics of CMS in pediatric population of Slovenia. METHODS: In this observational, national, cross-sectional study, medical records were retrospectively reviewed. Children with genetically confirmed CMS, referred over a 19 - year period (2000-2018) to the University Medical Centre, Ljubljana, Slovenia, were included in the study. Genetic and phenotypic characteristics were collected and prevalence of CMS in children was calculated. RESULTS: Eight children with a confirmed genetic mutation in 5 different genes (CHRNE, CHRND, RAPSN, CHAT, MUSK) causative of the CMS were identified. Calculated prevalence of genetically confirmed CMS was 22.2 cases per 1.000.000 children at the end of 2018. INTERPRETATION: The prevalence of genetically confirmed CMS in Slovenian children at the end of 2018 exceeds previously reported prevalence by more than two-fold, which suggests that prevalence in the literature is likely to be underestimated. Two extremely rarely detected mutations in MUSK and CHRND gene were detected and patient's clinical descriptions add important information on genotype-phenotype correlation.
AIM: Congenital myasthenic syndromes (CMS) are rare, genetically and phenotypically diverse disorders of neuromuscular transmission. Data on prevalence among children are scarce. Whole exome sequencing facilitated discovery of novel CMS mutations and enabled targeted treatment. Our aim was to identify the prevalence, genetic subtypes and clinical characteristics of CMS in pediatric population of Slovenia. METHODS: In this observational, national, cross-sectional study, medical records were retrospectively reviewed. Children with genetically confirmed CMS, referred over a 19 - year period (2000-2018) to the University Medical Centre, Ljubljana, Slovenia, were included in the study. Genetic and phenotypic characteristics were collected and prevalence of CMS in children was calculated. RESULTS: Eight children with a confirmed genetic mutation in 5 different genes (CHRNE, CHRND, RAPSN, CHAT, MUSK) causative of the CMS were identified. Calculated prevalence of genetically confirmed CMS was 22.2 cases per 1.000.000 children at the end of 2018. INTERPRETATION: The prevalence of genetically confirmed CMS in Slovenian children at the end of 2018 exceeds previously reported prevalence by more than two-fold, which suggests that prevalence in the literature is likely to be underestimated. Two extremely rarely detected mutations in MUSK and CHRND gene were detected and patient's clinical descriptions add important information on genotype-phenotype correlation.