Congenital Ophthalmoplegia and Late-Onset Limb Weakness Caused by MUSK Mutations.


Journal

Journal of clinical neuromuscular disease
ISSN: 1537-1611
Titre abrégé: J Clin Neuromuscul Dis
Pays: United States
ID NLM: 100887391

Informations de publication

Date de publication:
Jun 2020
Historique:
entrez: 27 5 2020
pubmed: 27 5 2020
medline: 27 4 2021
Statut: ppublish

Résumé

Congenital myasthenic syndromes are clinically and genetically heterogeneous disorders characterized by a neuromuscular transmission defect. Mutations in novel genes have been described in recent years. Among these, MUSK gene mutations are extremely rare, with only 8 families identified worldwide to date. We report a Spanish case, a carrier of one known hetero-allelic missense mutation and one newly identified MUSK gene variant. Our patient presented with congenital onset ophthalmoplegia and palpebral ptosis associated with limb-girdle weakness and exercise intolerance without prominent fatigability, developed during his twenties. He was misdiagnosed as mitochondrial myopathy because of paraclinic and histologic findings, but detailed clinical examination prompted us to reassess him with repetitive stimulation technique, demonstrating decremental response and suggesting myasthenic syndrome. A genetic study confirmed the clinical diagnosis allowing us to started treatment with excellent clinical response.

Identifiants

pubmed: 32453097
doi: 10.1097/CND.0000000000000277
pii: 00131402-202006000-00004
doi:

Substances chimiques

Receptors, Cholinergic 0
MUSK protein, human EC 2.7.10.1
Receptor Protein-Tyrosine Kinases EC 2.7.10.1

Types de publication

Case Reports Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

222-224

Références

Engel AG, Shen XM, Selcen D, et al. Congenital myasthenic syndromes: pathogenesis, diagnosis, and treatment. Lancet Neurol. 2015;14:420–434.
Luan X, Tian W, Cao L. Limb-girdle congenital myasthenic syndrome in a Chinese family with novel mutations in MUSK gene and literature review. Clin Neurol Neurosurg. 2016;150:41–45.
Richards S, Nazneen A, Bale S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17:405–424.
Giarrana ML, Joset P, Sticht H, et al. A severe congenital myasthenic syndrome with dropped head caused by novel MUSK mutations. Muscle Nerve. 2015;52:668–673.
Gallenmüller C, Müller-Felber W, Dusl M, et al. Salbutamol-responsive limb-girdle congenital myasthenic syndrome due to a novel missense mutation and heteroallelic deletion in MUSK. Neuromuscul Disord. 2014;24:31–35.
Maggi L, Brugnoni R, Scaioli V, et al. Marked phenotypic variability in two siblings with congenital myasthenic syndrome due to mutations in MUSK. J Neurol. 2013;260:2894–2896.
Chevessier F, Faraut B, Ravel-Chapuis A, et al. MUSK, a new target for mutations causing congenital myasthenic syndrome. Hum Mol Genet. 2004;13:3229–3240.
Ammar AB, Soltanzadeh P, Bauché S, et al. A mutation causes MuSK reduced sensitivity to agrin and congenital myasthenia. PLoS One. 2013;8:e53826.
Mihaylova V, Salih MA, Mukhtar MM, et al. Refinement of the clinical phenotype in musk-related congenital myasthenic syndromes. Neurology. 2009;73:1926–1928.
Maselli RA, Arredondo J, Cagney Ó, et al. Mutations in MUSK causing congenital myasthenic syndrome impair MuSK-Dok-7 interaction. Hum Mol Genet. 2010;19:2370–2379.
Kao JC, Milone M, Selcen D, et al. Congenital myasthenic syndromes in adult neurology clinic: a long road to diagnosis and therapy. Neurology. 2018;91:e1770–e1777.
Martignago S, Fanin M, Albertini E, et al. Muscle histopathology in myasthenia gravis with antibodies against MuSK and AChR. Neuropathol Appl Neurobiol. 2009;35:103–110.

Auteurs

Fernando Ostos (F)

Neurology Department, Hospital Universitario 12 de Octubre, Madrid, Spain.

Pilar Alcantara Miranda (P)

Neurology Department, Hospital Universitario de La Princesa, Madrid, Spain.

Aurelio Hernández-Laín (A)

Pathology Department (Neuropathology), Hospital Universitario 12 de Octubre, Madrid, Spain.

Cristina Domínguez-González (C)

Neurology Department, Neuromuscular Unit, Hospital Universitario 12 de Octubre, Madrid, Spain; and.
Centro de Investigación en Red de Enfermedades Raras (CIBERER, U723), Valencia, Spain.

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Classifications MeSH