The clinical spectrum of the congenital myasthenic syndrome resulting from COL13A1 mutations
Rodríguez Cruz, Pedro M. (John Radcliffe Hospital (Oxford, Regne Unit))
Cossins, Judith (Neurosciences Group. Nuffield Department of Clinical Neurosciences. Weatherall Institute of Molecular Medicine. University of Oxford)
De Paula Estephan, Eduardo (Departamento de Neurologia. Faculdade de Medicina. Universidade de São Paulo (FMUSP))
Munell Casadesus, Francina (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Selby, KKathryn (University of British Columbia)
Hirano, Michio (Department of Neurology. H. Houston Merritt Neuromuscular Research Center. Columbia University Medical Center)
Maroofin, Reza (Molecular and Clinical Sciences Institute. St. George's. University of London)
Mehrjardi, Mohammad Yahya Vahid (Medical Genetics Research Centre. Shahid Sadoughi University of Medical Sciences)
Chow, Gabriel (Nottingham University Hospitals NHS Trust (Regne Unit))
Carr, Aislin (MRC Centre for Neuromuscular Diseases. National Hospital for Neurology and Neurosurgery)
Manzur, Adnan (Dubowitz Neuromuscular Centre. MRC Centre for Neuromuscular Diseases. UCL Great Ormond Street Institute of Child Health)
Robb, Stephanie (Dubowitz Neuromuscular Centre. MRC Centre for Neuromuscular Diseases. UCL Great Ormond Street Institute of Child Health)
Munot, Pinki (Dubowitz Neuromuscular Centre. MRC Centre for Neuromuscular Diseases. UCL Great Ormond Street Institute of Child Health)
Wei Liu, Wei (Neurosciences Group. Nuffield Department of Clinical Neurosciences. Weatherall Institute of Molecular Medicine. University of Oxford)
Banka, Siddharth (Manchester Centre for Genomic Medicine. St Mary's Hospital. Manchester University NHS Foundation Trust. Health Innovation Manchester)
Fraser, Harry (Manchester Centre for Genomic Medicine. St Mary's Hospital. Manchester University NHS Foundation Trust. Health Innovation Manchester)
De Goede, Christian (Department of Paediatric Neurology. Royal Preston Hospital)
Zanoteli, Edmar (Departamento de Neurologia. Faculdade de Medicina. Universidade de São Paulo (FMUSP))
Conti Reed, Umbertina (Departamento de Neurologia. Faculdade de Medicina. Universidade de São Paulo (FMUSP))
Sage, Abigail (Department of Neurology. H. Houston Merritt Neuromuscular Research Center. Columbia University Medical Center)
Gratacòs-Viñola, Margarida (Hospital Universitari Vall d'Hebron)
Macaya Ruiz, Alfons (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Dusl, Marina (Friedrich-Baur-Institute. Department of Neurology. University Hospital LMU Munich)
Senderek, Jan (Friedrich-Baur-Institute. Department of Neurology. University Hospital LMU Munich)
Töpf, Ana (Institute of Genetic Medicine)
Hofer, Monika (John Radcliffe Hospital (Oxford, Regne Unit))
Knight, Ravi (John Radcliffe Hospital (Oxford, Regne Unit))
Ramdas, Sithara (Department of Paediatric Neurology. John Radcliffe Hospital NHS Foundation Trust)
Jayawant, Sandeep (Department of Paediatric Neurology. John Radcliffe Hospital NHS Foundation Trust)
Lochmüller, Hans (Division of Neurology. Department of Medicine. Ottawa Hospital)
Palace, Jacqueline (John Radcliffe Hospital (Oxford, Regne Unit))
Beeson, David (Neurosciences Group. Nuffield Department of Clinical Neurosciences. Weatherall Institute of Molecular Medicine. University of Oxford)
Universitat Autònoma de Barcelona

Fecha:	2019
Resumen:	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.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Congenital myasthenic syndromes ; COL13A1 ; Synaptic basal lamina ; Salbutamol ; 3,4-diaminopyridine
Publicado en:	Brain, Vol. 142 Núm. 6 (january 2019) , p. 1547-1560, ISSN 1460-2156

DOI: 10.1093/brain/awz107
PMID: 31081514

9 p, 359.6 KB

El registro aparece en las colecciones:
Artículos > Artículos de investigación
Artículos > Artículos publicados