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Journal of Neurology

, Volume 266, Issue 5, pp 1107–1112 | Cite as

Congenital myasthenic syndrome caused by novel COL13A1 mutations

  • Marina DuslEmail author
  • Teresa Moreno
  • Francina Munell
  • Alfons Macaya
  • Margarida Gratacòs
  • Angela Abicht
  • Tim M. Strom
  • Hanns Lochmüller
  • Jan Senderek
Original Communication
  • 172 Downloads

Abstract

Collagen XIII is a non-fibrillar transmembrane collagen which has been long recognized for its critical role in synaptic maturation of the neuromuscular junction. More recently, biallelic COL13A1 loss-of-function mutations were identified in three patients with congenital myasthenic syndrome (CMS), a rare inherited condition with defective neuromuscular transmission, causing abnormal fatigability and fluctuating muscle weakness and often successfully treated with acetylcholinesterase inhibitors. Here we report six additional CMS patients from three unrelated families with previously unreported homozygous COL13A1 loss-of-function mutations (p.Tyr216*, p.Glu543fs and p.Thr629fs). The phenotype of our cases was similar to the previously reported patients including respiratory distress and severe dysphagia at birth that often resolved or improved in the first days or weeks of life. All individuals had prominent eyelid ptosis with only minor ophthalmoparesis as well as generalized muscle weakness, predominantly affecting facial, bulbar, respiratory and axial muscles. Response to acetylcholinesterase inhibitor treatment was generally negative while salbutamol proved beneficial. Our data further support the causality of COL13A1 variants for CMS and suggest that this type of CMS might be clinically homogenous and requires alternative pharmacological therapy.

Keywords

COL13A1 Collagen type XIII alpha 1 chain Autosomal recessive Congenital myasthenic syndrome Neuromuscular junction 

Notes

Acknowledgements

We thank the families for participating in this study. M. Dusl is a postdoctoral fellow of the Bayerische Gleichstellungsförderung (BGF). This work was supported by the Fritz-Thyssen-Stiftung (Az.10.15.1.021MN; to J. Senderek).

Compliance with ethical standards

Conflicts of interest

The authors declare no conflict of interest.

Supplementary material

415_2019_9239_MOESM1_ESM.docx (25 kb)
Supplementary material 1 (DOCX 25 KB)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Neurology, Friedrich-Baur-InstituteUniversity Hospital, LMU MunichMunichGermany
  2. 2.Unidade de NeuropediatriaCentro Hospitalar Universitário Lisboa NorteLisbonPortugal
  3. 3.Department of Pediatric NeurologyHospital Universitari Materno-Infantil Vall d’HebronBarcelonaSpain
  4. 4.Department of NeurophysiologyHospital Universitari Materno-Infantil Vall d’HebronBarcelonaSpain
  5. 5.Institute of Human GeneticsHelmholtz Zentrum MünchenNeuherbergGermany
  6. 6.Institute of Human GeneticsTechnische Universität MünchenMunichGermany
  7. 7.Department of Neuropediatrics and Muscle Disorders, Medical CenterUniversity of FreiburgFreiburgGermany
  8. 8.Centro Nacional de Análisis Genómico (CNAG-CRG), Center for Genomic RegulationBarcelona Institute of Science and Technology (BIST)BarcelonaSpain
  9. 9.Children’s Hospital of Eastern Ontario Research InstituteUniversity of OttawaOttawaCanada
  10. 10.Division of Neurology, Department of MedicineThe Ottawa HospitalOttawaCanada

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