title: Late presentations of congenital myasthenic syndromes: How many do we miss?
abstract: Congenital myasthenic syndromes (CMS) usually present neonatally or in early childhood. When they present later, they may be mistaken for seronegative autoimmune myasthenia, and unnecessary immunosuppressive treatment may be administered.
  
  
  
  Patients who met criteria for seronegative generalized myasthenia without congenital or early childhood onset, but with an affected sibling were tested for CMS associated genes using exome and Sanger sequencing.
  
  
  
  Four sibling pairs from nonconsanguineous families were identified. Three had mutations in the RAPSN gene, and 1 had a mutation in CHRNA1. One sibling of a pair with symptoms of fatigue but no convincing features of neuromuscular dysfunction tested negative on genetic studies. The definite CMS cases comprised 7 of 25 seronegative patients with definite generalized myasthenia in the clinic, and over half had been treated for autoimmune myasthenia.
  
  
  
  CMS is probably underdiagnosed in seronegative myasthenic disorders and should be considered in the differential diagnosis. Muscle Nerve 54: 721-727, 2016.
authors.affiliation: Neuroimmunology Clinic, Concord Hospital and University of Sydney, NSW, Australia.
authors.forename: Nidhi
authors.identifier: 0000-0003-1563-6792
authors.initials: N
authors.lastname: Garg
authors.affiliation: Departments of Neurology and Molecular Medicine, University of Sydney, Concord Hospital, Sydney, New South Wales, 2139, Australia.
authors.forename: Con
authors.initials: C
authors.lastname: Yiannikas
authors.affiliation: Neuroimmunology Clinic, Concord Hospital and University of Sydney, NSW, Australia.
authors.forename: Todd A
authors.initials: TA
authors.lastname: Hardy
authors.affiliation: The Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.
authors.forename: Katsiaryna
authors.initials: K
authors.lastname: Belaya
authors.affiliation: The Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Cheung
authors.affiliation: The Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.
authors.forename: David
authors.initials: D
authors.lastname: Beeson
authors.affiliation: Neuroimmunology Clinic, Concord Hospital and University of Sydney, NSW, Australia. swreddel@sydneyneurology.com.au.
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Reddel
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020294:Myasthenic Syndromes, Congenital / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology*; D055815:Young Adult
keywords: CHRNA1; RAPSN; congenital myasthenic syndrome; genetics; myasthenia gravis; seronegative