Journal of Neurology

, Volume 263, Issue 3, pp 517–523 | Cite as

KLHL40-related nemaline myopathy with a sustained, positive response to treatment with acetylcholinesterase inhibitors

  • D. Natera-de Benito
  • A. Nascimento
  • A. Abicht
  • C. Ortez
  • C. Jou
  • J. S. Müller
  • T. Evangelista
  • A. Töpf
  • R. Thompson
  • C. Jimenez-Mallebrera
  • J. Colomer
  • H. Lochmüller
Original Communication


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.


KLHL40 Congenital myopathies Nemaline myopathies Neuromuscular junction Acetylcholinesterase inhibitors Congenital myasthenic syndromes 



The authors would like to thank the family for taking part in this study.

The Institute of Genetic Medicine in Newcastle is part of the MRC Centre for Neuromuscular Diseases and the TREAT-NMD Alliance ( This study was supported by the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement No. 305444 (RD-Connect) and 305121 (Neuromics).

We are indebted to the ‘Biobanc de l’Hospital Infantil Sant Joan de Deu per a la Investigacio’, integrated in the Spanish Biobank network of ISCIII, for sample procurement.

Compliance with ethical standards

Conflicts of interest


Ethical standards

The study was approved by the ethics committee.

Supplementary material

Supplementary material 1 (MPG 2674 kb)

Supplementary material 2 (MPG 2287 kb)

415_2015_8015_MOESM3_ESM.mpg (2.6 mb)
Supplementary material 3 (MPG 2640 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • D. Natera-de Benito
    • 1
  • A. Nascimento
    • 2
  • A. Abicht
    • 3
    • 4
  • C. Ortez
    • 2
  • C. Jou
    • 5
  • J. S. Müller
    • 6
  • T. Evangelista
    • 6
  • A. Töpf
    • 6
  • R. Thompson
    • 6
  • C. Jimenez-Mallebrera
    • 2
    • 7
  • J. Colomer
    • 2
  • H. Lochmüller
    • 6
  1. 1.Department of PediatricsHospital Universitario de FuenlabradaMadridSpain
  2. 2.Department of Neuromuscular DiseasesHospital Sant Joan de DéuBarcelonaSpain
  3. 3.Friedrich-Baur-InstituteLudwig-Maximilians-University MunichMunichGermany
  4. 4.Medical Genetics CenterMunichGermany
  5. 5.Pathology DepartmentHospital Sant Joan de DéuBarcelonaSpain
  6. 6.John Walton Muscular Dystrophy Research Centre, MRC Centre for Neuromuscular Diseases, Institute of Genetic MedicineNewcastle UniversityNewcastle upon TyneUK
  7. 7.Center for Biomedical Research on Rare Diseases (CIBERER)Instituto de Salud Carlos IIIMadridSpain

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