Case ReviewCongenital Ophthalmoplegia and Late-Onset Limb Weakness Caused by MUSK MutationsOstos, Fernando MD*; Alcantara Miranda, Pilar MD†; Hernández-Laín, Aurelio MD, PhD‡; Domínguez-González, Cristina MD§,¶Author Information *Neurology Department, Hospital Universitario 12 de Octubre, Madrid, Spain; †Neurology Department, Hospital Universitario de La Princesa, Madrid, Spain; ‡Pathology Department (Neuropathology), Hospital Universitario 12 de Octubre, Madrid, Spain; §Neurology Department, Neuromuscular Unit, Hospital Universitario 12 de Octubre, Madrid, Spain; and ¶Centro de Investigación en Red de Enfermedades Raras (CIBERER, U723), Valencia, Spain. Reprints: Fernando Ostos, Neurology Department, Hospital Universitario 12 de Octubre, Avenida de Córdoba, s/n, Madrid 28041, Spain (e-mail: firstname.lastname@example.org). The authors report no conflicts of interest. Journal of Clinical Neuromuscular Disease: June 2020 - Volume 21 - Issue 4 - p 222-224 doi: 10.1097/CND.0000000000000277 Buy Metrics Abstract 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. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.