The clinical spectrum of the congenital myasthenic syndrome resulting from COL13A1 mutations.

Autor:	Rodríguez Cruz PM; Neurosciences Group, Nuffield Department of Clinical Neurosciences, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.; Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford, UK., Cossins J; Neurosciences Group, Nuffield Department of Clinical Neurosciences, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK., Estephan EP; Departamento de Neurologia, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil., Munell F; Neuromuscular disorders Group, Child Neurology Unit, Hospital Universitari Vall d'Hebron, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain., Selby K; University of British Columbia, Vancouver, British Columbia, Canada., Hirano M; Department of Neurology, H. Houston Merritt Neuromuscular Research Center, Columbia University Medical Center, New York, NY, USA., Maroofin R; Molecular and Clinical Sciences Institute, St. George's, University of London, Cranmer Terrace, London, UK., Mehrjardi MYV; Medical Genetics Research Centre, Shahid Sadoughi University of Medical Sciences, Yazd, Iran., Chow G; Department of Paediatric Neurology, Nottingham City Hospital, Nottingham University Hospitals NHS Trust, Hucknall Road, Nottingham, UK., Carr A; MRC Centre for Neuromuscular Diseases, National Hospital for Neurology and Neurosurgery, London, UK., Manzur A; Dubowitz Neuromuscular Centre and MRC Centre for Neuromuscular Diseases, UCL Great Ormond Street Institute of Child Health, London, UK., Robb S; Dubowitz Neuromuscular Centre and MRC Centre for Neuromuscular Diseases, UCL Great Ormond Street Institute of Child Health, London, UK., Munot P; Dubowitz Neuromuscular Centre and MRC Centre for Neuromuscular Diseases, UCL Great Ormond Street Institute of Child Health, London, UK., Wei Liu W; Neurosciences Group, Nuffield Department of Clinical Neurosciences, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK., Banka S; Manchester Centre for Genomic Medicine, St Mary's Hospital, Manchester University NHS Foundation Trust, Health Innovation Manchester, Manchester, UK., Fraser H; Manchester Centre for Genomic Medicine, St Mary's Hospital, Manchester University NHS Foundation Trust, Health Innovation Manchester, Manchester, UK., De Goede C; Department of Paediatric Neurology, Royal Preston Hospital, Preston, UK., Zanoteli E; Departamento de Neurologia, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil., Conti Reed U; Departamento de Neurologia, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil., Sage A; Department of Neurology, H. Houston Merritt Neuromuscular Research Center, Columbia University Medical Center, New York, NY, USA., Gratacos M; Department of Clinical Neurophysiology, Hospital Universitari Vall d'Hebron, Barcelona Spain., Macaya A; Neuromuscular disorders Group, Child Neurology Unit, Hospital Universitari Vall d'Hebron, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain., Dusl M; Friedrich-Baur-Institute at the Department of Neurology, University Hospital LMU Munich, Munich, Germany., Senderek J; Friedrich-Baur-Institute at the Department of Neurology, University Hospital LMU Munich, Munich, Germany., Töpf A; Institute of Genetic Medicine, Central Parkway, Newcastle upon Tyne, UK., Hofer M; Department of Neuropathology, John Radcliffe Hospital NHS Foundation Trust, Oxford, UK., Knight R; Department of Clinical Neurophysiology, John Radcliffe Hospital NHS Foundation Trust, Oxford, UK., Ramdas S; Department of Paediatric Neurology, John Radcliffe Hospital NHS Foundation Trust, Oxford, UK., Jayawant S; Department of Paediatric Neurology, John Radcliffe Hospital NHS Foundation Trust, Oxford, UK., Lochmüller H; Department of Neuropediatrics and Muscle Disorders, Medical Center-University of Freiburg, Faculty of Medicine, Freiburg, Germany.; Centro Nacional de Análisis Genómico (CNAG-CRG), Center for Genomic Regulation, Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.; Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Canada.; Division of Neurology, Department of Medicine, The Ottawa Hospital, Ottawa, Canada., Palace J; Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford, UK., Beeson D; Neurosciences Group, Nuffield Department of Clinical Neurosciences, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
Jazyk:	angličtina
Zdroj:	Brain : a journal of neurology [Brain] 2019 Jun 01; Vol. 142 (6), pp. 1547-1560.
DOI:	10.1093/brain/awz107
Abstrakt:	Next generation sequencing techniques were recently used to show mutations in COL13A1 cause synaptic basal lamina-associated congenital myasthenic syndrome type 19. Animal studies showed COL13A1, a synaptic extracellular-matrix protein, is involved in the formation and maintenance of the neuromuscular synapse that appears independent of the Agrin-LRP4-MuSK-DOK7 acetylcholine receptor clustering pathway. Here, we report the phenotypic spectrum of 16 patients from 11 kinships harbouring homozygous or heteroallelic mutations in COL13A1. Clinical presentation was mostly at birth with hypotonia and breathing and feeding difficulties often requiring ventilation and artificial feeding. Respiratory crisis related to recurrent apnoeas, sometimes triggered by chest infections, were common early in life but resolved over time. The predominant pattern of muscle weakness included bilateral ptosis (non-fatigable in adulthood), myopathic facies and marked axial weakness, especially of neck flexion, while limb muscles were less involved. Other features included facial dysmorphism, skeletal abnormalities and mild learning difficulties. All patients tested had results consistent with abnormal neuromuscular transmission. Muscle biopsies were within normal limits or showed non-specific changes. Muscle MRI and serum creatine kinase levels were normal. In keeping with COL13A1 mutations affecting both synaptic structure and presynaptic function, treatment with 3,4-diaminopyridine and salbutamol resulted in motor and respiratory function improvement. In non-treated cases, disease severity and muscle strength improved gradually over time and several adults recovered normal muscle strength in the limbs. In summary, patients with COL13A1 mutations present mostly with severe early-onset myasthenic syndrome with feeding and breathing difficulties. Axial weakness is greater than limb weakness. Disease course improves gradually over time, which could be consistent with the less prominent role of COL13A1 once the neuromuscular junction is mature. This report emphasizes the role of collagens at the human muscle endplate and should facilitate the recognition of this disorder, which can benefit from pharmacological treatment. (© The Author(s) (2019). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
Databáze:	MEDLINE
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