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J Neurol. 2019 May;266(5):1107-1112. doi: 10.1007/s00415-019-09239-7. Epub 2019 Feb 14.

Congenital myasthenic syndrome caused by novel COL13A1 mutations.

Author information

1
Department of Neurology, Friedrich-Baur-Institute, University Hospital, LMU Munich, Marchioninistrasse 17, 81377, Munich, Germany. marina.dusl@med.uni-muenchen.de.
2
Unidade de Neuropediatria, Centro Hospitalar Universitário Lisboa Norte, Lisbon, Portugal.
3
Department of Pediatric Neurology, Hospital Universitari Materno-Infantil Vall d'Hebron, Barcelona, Spain.
4
Department of Neurophysiology, Hospital Universitari Materno-Infantil Vall d'Hebron, Barcelona, Spain.
5
Department of Neurology, Friedrich-Baur-Institute, University Hospital, LMU Munich, Marchioninistrasse 17, 81377, Munich, Germany.
6
Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany.
7
Institute of Human Genetics, Technische Universität München, Munich, Germany.
8
Department of Neuropediatrics and Muscle Disorders, Medical Center, University of Freiburg, Freiburg, Germany.
9
Centro Nacional de Análisis Genómico (CNAG-CRG), Center for Genomic Regulation, Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.
10
Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Canada.
11
Division of Neurology, Department of Medicine, The Ottawa Hospital, Ottawa, Canada.

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:

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

PMID:
30767057
DOI:
10.1007/s00415-019-09239-7

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