Nidhi Garg1, Con Yiannikas2, Todd A Hardy1, Katsiaryna Belaya3, Jonathan Cheung3, David Beeson3, Stephen W Reddel4. 1. Neuroimmunology Clinic, Concord Hospital and University of Sydney, NSW, Australia. 2. Departments of Neurology and Molecular Medicine, University of Sydney, Concord Hospital, Sydney, New South Wales, 2139, Australia. 3. The Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK. 4. Neuroimmunology Clinic, Concord Hospital and University of Sydney, NSW, Australia. swreddel@sydneyneurology.com.au.
Abstract
INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: CMS is probably underdiagnosed in seronegative myasthenic disorders and should be considered in the differential diagnosis. Muscle Nerve 54: 721-727, 2016.
INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: CMS is probably underdiagnosed in seronegative myasthenic disorders and should be considered in the differential diagnosis. Muscle Nerve 54: 721-727, 2016.
Authors: Yoshiteru Azuma; Ana Töpf; Teresinha Evangelista; Paulo José Lorenzoni; Andreas Roos; Pedro Viana; Hidehito Inagaki; Hiroki Kurahashi; Hanns Lochmüller Journal: Neurol Genet Date: 2017-05-03