Prevelance in congenital myasthenic syndrome

Congenital myasthenic syndromes (CMS) constitute a group of genetically and phenotypically heterogeneous, mostly early-onset, neuromuscular transmission disorders due to variants in genes encoding proteins involved in the organisation, maintenance, and function of the motor endplate (endplate myopathies) [ [1] Finsterer J. Congenital myasthenic syndromes. Orphanet J. Rare Dis. 2019; 14: 57https://doi.org/10.1186/s13023-019-1025-5 Crossref PubMed Scopus (41) Google Scholar ]. Phenotypically, CMS manifest with increased fatigability and transient or permanent weakness of extra-ocular, facial, bulbar, truncal, respiratory, or limb muscles [ [1] Finsterer J. Congenital myasthenic syndromes. Orphanet J. Rare Dis. 2019; 14: 57https://doi.org/10.1186/s13023-019-1025-5 Crossref PubMed Scopus (41) Google Scholar ]. Clinical severity varies considerably between mild, transient weakness and permanent weakness, respiratory insufficiency, and premature death [ [1] Finsterer J. Congenital myasthenic syndromes. Orphanet J. Rare Dis. 2019; 14: 57https://doi.org/10.1186/s13023-019-1025-5 Crossref PubMed Scopus (41) Google Scholar ]. Rarely, additional features such as cognitive impairment, dysmorphism, neuropathy, or epilepsy can be found [ [1] Finsterer J. Congenital myasthenic syndromes. Orphanet J. Rare Dis. 2019; 14: 57https://doi.org/10.1186/s13023-019-1025-5 Crossref PubMed Scopus (41) Google Scholar ]. Age at onset, presenting symptoms, disease trajectory, and response to treatment vary depending on the genetic cause and pathophysiology. CMS are categorized as pre-synaptic (SLC5A7, CHAT, LC18A3, SNAP25, VAMP1, SYB1, SYT2, MUNC13-1), synaptic (COLQ, LAMB2, LAMA5, COL13A1), post-synaptic (CHRNA1, CHRNB1, CHRND, CHRNE, CHRNG, FCCMS, SCCMS, DOK7, MUSK, MYO9A, AGRN, LRP4, PREPL, SCN4A, RAPSN, PLEC1, SLC25A1) and as glycosylation defects (GFPT1, GMPPB, ALG2, ALG14, DPAGT1). Gene products encoded by these genes function as ion-channel, enzymatic, structural, signalling, sensor, or transporter proteins [ [1] Finsterer J. Congenital myasthenic syndromes. Orphanet J. Rare Dis. 2019; 14: 57https://doi.org/10.1186/s13023-019-1025-5 Crossref PubMed Scopus (41) Google Scholar ]. The prevalence of CMS varies considerably between regions. In a UK-based study the prevalence varied between 2.8 and 14.8/1000000 [ [2] Parr J.R. Andrew M.J. Finnis M. Beeson D. Vincent A. Jayawant S. How common is childhood myasthenia? The UK incidence and prevalence of autoimmune and congenital myasthenia. Arch. Dis. Child. 2014; 99: 539-542 Crossref PubMed Scopus (44) Google Scholar ]. In a Brazilian study the prevalence was calculated as 1.8/1000000 [ [3] Mihaylova V. Scola R.H. Gervini B. Lorenzoni P.J. Kay C.K. Werneck L.C. Stucka R. Guergueltcheva V. von der Hagen M. Huebner A. Abicht A. Müller J.S. Lochmüller H. Molecular characterisation of congenital myasthenic syndromes in Southern Brazil. J. Neurol. Neurosurg. Psychiatry. 2010; 81: 973-977 Crossref PubMed Scopus (34) Google Scholar ]. In a recent review the prevalence was estimated as 1/10 that of myasthenia gravis, resulting in a CMS prevalence of 25–125/1000000 [ [4] Abicht A. Müller J.S. Lochmüller H. Congenital myasthenic syndromes. in: Adam M.P. Ardinger H.H. Pagon R.A. Wallace S.E. Bean L.J.H. Mefford H.C. Stephens K. Amemiya A. Ledbetter N. GeneReviews®. University of Washington, Seattle, Seattle (WA)2003 May 9: 1993-2017http://www.ncbi.nlm.nih.gov/books/NBK1168/ Google Scholar ]. The most commonly mutated genes in CMS include CHAT, COLQ, RAPSN, CHRNE, DOK7, GFPT1, CHRNB1, CHRND, and MUSK. CMS is diagnosed upon the individual and family history, clinical exam, low- and high-frequency repetitive nerve stimulation, absence of antibodies against the acetyl-choline receptor, MUSK, LRP4, and agrin, and upon next generation sequencing (NGS). Prevalence and genetic subtypes of congenital myasthenic syndromes in the pediatric population of SloveniaEuropean Journal of Paediatric NeurologyVol. 26PreviewThe 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. Full-Text PDF