title: Congenital myasthenic syndrome due to mutation in CHRNE gene with clinical worsening and thymic hyperplasia attributed to association with autoimmune-myasthenia gravis.
abstract: We report a patient with congenital myasthenic syndrome (CMS) due to mutation in CHRNE with symptoms since the age of 4; mild to moderate fatigable weakness involved mainly ocular, bulbar and limb muscles; functional impact of the disease in their development and physical activity was modest. By the age of 34, the patient experienced gradual worsening of fatigue with dyspnoea and pronounced limb weakness, requiring significant increase of pyridostigmine. Further, a remarkable and sustained clinical improvement followed thymectomy with hyperplastic thymus. Despite of the absence of detectable antibodies to acetyl-choline receptor (AChR) (including clustered-AChR), muscle-specific kinase and low-density lipoprotein receptor-related protein-4 antibodies in the serum obtained nine years after thymectomy, the clinical, genetic and histological features are in keeping with the extremely rare association of two rare neuromuscular junction disorders - CMS and myasthenia gravis (MG). The inexistence of other conditions that could potentially associate with thymic hyperplasia also supports the diagnosis of MG.
authors.affiliation: Neurology Department, Hospital Santo António, Centro Hospitalar Porto, Portugal.
authors.forename: Ernestina
authors.initials: E
authors.lastname: Santos
authors.affiliation: Neurology Department, Hospital Santo António, Centro Hospitalar Porto, Portugal.
authors.forename: Isabel
authors.initials: I
authors.lastname: Moreira
authors.affiliation: Nuffield Department of Clinical Neurosciences, Oxford University Hospitals, University of Oxford, UK.
authors.forename: Ester
authors.initials: E
authors.lastname: Coutinho
authors.affiliation: Institute of Biomedical Sciences Abel Salazar, University of Porto, Portugal.
authors.forename: Guilherme
authors.initials: G
authors.lastname: Gonçalves
authors.affiliation: Pathology and Molecular Immunology Department, Institute of Biomedical Sciences Abel Salazar, University of Porto, Portugal.
authors.forename: Carlos
authors.initials: C
authors.lastname: Lopes
authors.affiliation: Neurology Department, Hospital Santo António, Centro Hospitalar Porto, Portugal.
authors.forename: José
authors.initials: J
authors.lastname: Lopes Lima
authors.affiliation: Nuffield Department of Clinical Neurosciences, Oxford University Hospitals, University of Oxford, UK. Electronic address: maria.leite@ndcn.ox.ac.uk.
authors.forename: M Isabel
authors.initials: MI
authors.lastname: Leite
mesh_terms: D000328:Adult; D018450:Disease Progression; D006801:Humans; D008297:Male; D018482:Muscle, Skeletal / Q000503:physiopathology; D009154:Mutation; D009157:Myasthenia Gravis / Q000150:complications* / Q000503:physiopathology; D020294:Myasthenic Syndromes, Congenital / Q000150:complications* / Q000235:genetics* / Q000503:physiopathology; D011978:Receptors, Nicotinic / Q000235:genetics*; D013934:Thymectomy; D013952:Thymus Hyperplasia / Q000150:complications* / Q000601:surgery
chemical_list: C504423:CHRNE protein, human; D011978:Receptors, Nicotinic
keywords: Congenital myasthenic syndrome; Myasthenia gravis; Neuromuscular junction disorder