title: KLHL40-related nemaline myopathy with a sustained, positive response to treatment with acetylcholinesterase inhibitors.
abstract: Congenital myopathies are a group of inherited muscle disorders characterized by hypotonia, weakness and a non-dystrophic muscle biopsy with the presence of one or more characteristic histological features. Neuromuscular transmission defects have recently been reported in several patients with congenital myopathies (CM). Mutations in KLHL40 are among the most common causes of severe forms of nemaline myopathy. Clinical features of affected individuals include fetal akinesia or hypokinesia, respiratory failure, and swallowing difficulties at birth. Muscle weakness is usually severe and nearly half of the individuals have no spontaneous antigravity movement. The average age of death has been reported to be 5 months in a recent case series. Herein we present a case of a patient with a nemaline myopathy due to KLHL40 mutations (c.604delG, p.Ala202Argfs*56 and c.1513G>C, p.Ala505Pro) with an impressive and prolonged beneficial response to treatment with high-dose pyridostigmine. Myasthenic features or response to ACEI have not previously been reported as a characteristic of nemaline myopathy or KLHL40-related myopathy.
authors.affiliation: Department of Pediatrics, Hospital Universitario de Fuenlabrada, Madrid, Spain. daninatera@hotmail.com.
authors.forename: D
authors.initials: D
authors.lastname: Natera-de Benito
authors.affiliation: Department of Neuromuscular Diseases, Hospital Sant Joan de Déu, Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Nascimento
authors.affiliation: Friedrich-Baur-Institute, Ludwig-Maximilians-University Munich, 80336, Munich, Germany.|Medical Genetics Center, Munich, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Abicht
authors.affiliation: Department of Neuromuscular Diseases, Hospital Sant Joan de Déu, Barcelona, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Ortez
authors.affiliation: Pathology Department, Hospital Sant Joan de Déu, Barcelona, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Jou
authors.affiliation: John Walton Muscular Dystrophy Research Centre, MRC Centre for Neuromuscular Diseases, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, NE1 3BZ, UK.
authors.forename: J S
authors.initials: JS
authors.lastname: Müller
authors.affiliation: John Walton Muscular Dystrophy Research Centre, MRC Centre for Neuromuscular Diseases, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, NE1 3BZ, UK.
authors.forename: T
authors.initials: T
authors.lastname: Evangelista
authors.affiliation: John Walton Muscular Dystrophy Research Centre, MRC Centre for Neuromuscular Diseases, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, NE1 3BZ, UK.
authors.forename: A
authors.initials: A
authors.lastname: Töpf
authors.affiliation: John Walton Muscular Dystrophy Research Centre, MRC Centre for Neuromuscular Diseases, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, NE1 3BZ, UK.
authors.forename: R
authors.initials: R
authors.lastname: Thompson
authors.affiliation: Department of Neuromuscular Diseases, Hospital Sant Joan de Déu, Barcelona, Spain.|Center for Biomedical Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Jimenez-Mallebrera
authors.affiliation: Department of Neuromuscular Diseases, Hospital Sant Joan de Déu, Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Colomer
authors.affiliation: John Walton Muscular Dystrophy Research Centre, MRC Centre for Neuromuscular Diseases, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, NE1 3BZ, UK.
authors.forename: H
authors.initials: H
authors.lastname: Lochmüller
mesh_terms: D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007223:Infant; D008137:Longitudinal Studies; D009124:Muscle Proteins / Q000235:genetics* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D017696:Myopathies, Nemaline / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D009460:Neurologic Examination
chemical_list: D002800:Cholinesterase Inhibitors; C000595273:KLHL40 protein, human; D009124:Muscle Proteins
keywords: Acetylcholinesterase inhibitors; Congenital myasthenic syndromes; Congenital myopathies; KLHL40; Nemaline myopathies; Neuromuscular junction