Prevalence and genetic subtypes of congenital myasthenic syndromes in the pediatric population of Slovenia

Anja Troha Gergeli; David Neubauer; Tanja Golli; Tita Butenko; Tanja Loboda; Aleš Maver; Damjan Osredkar

doi:10.1016/j.ejpn.2020.02.002

Prevalence and genetic subtypes of congenital myasthenic syndromes in the pediatric population of Slovenia

Eur J Paediatr Neurol. 2020 May:26:34-38. doi: 10.1016/j.ejpn.2020.02.002. Epub 2020 Feb 11.

Authors

Anja Troha Gergeli¹, David Neubauer², Tanja Golli², Tita Butenko¹, Tanja Loboda¹, Aleš Maver³, Damjan Osredkar⁴

Affiliations

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.

PMID: 32070632
DOI: 10.1016/j.ejpn.2020.02.002

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.

Keywords: Child; Congenital myasthenic syndromes; Genetic confirmation; Treatment.

Publication types

Observational Study

MeSH terms

Adolescent
Child
Cross-Sectional Studies
Female
Humans
Male
Mutation
Myasthenic Syndromes, Congenital / diagnosis
Myasthenic Syndromes, Congenital / epidemiology*
Myasthenic Syndromes, Congenital / genetics*
Prevalence
Retrospective Studies
Slovenia / epidemiology