Delayed Diagnosis of Congenital Myasthenic Syndromes Erroneously Interpreted as Mitochondrial Myopathies
Background: Congenital myasthenic syndromes (CMSs) and primary mitochondrial myopathies (PMMs) can present with ptosis, external ophthalmoplegia, and limb weakness. Methods: Our method involved the description of three cases of CMS that were initially characterized as probable PMM. Results: All pati...
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| Format: | Article |
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MDPI AG
2023-05-01
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| Series: | Journal of Clinical Medicine |
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| Online Access: | https://www.mdpi.com/2077-0383/12/9/3308 |
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| author | Mariana I. Muñoz-García María Paz Guerrero-Molina Carlos Pablo de Fuenmayor-Fernández de la Hoz Laura Bermejo-Guerrero Ana Arteche-López Aurelio Hernández-Laín Miguel A. Martín Cristina Domínguez-González |
| author_facet | Mariana I. Muñoz-García María Paz Guerrero-Molina Carlos Pablo de Fuenmayor-Fernández de la Hoz Laura Bermejo-Guerrero Ana Arteche-López Aurelio Hernández-Laín Miguel A. Martín Cristina Domínguez-González |
| author_sort | Mariana I. Muñoz-García |
| collection | DOAJ |
| description | Background: Congenital myasthenic syndromes (CMSs) and primary mitochondrial myopathies (PMMs) can present with ptosis, external ophthalmoplegia, and limb weakness. Methods: Our method involved the description of three cases of CMS that were initially characterized as probable PMM. Results: All patients were male and presented with ptosis and/or external ophthalmoplegia at birth, with proximal muscle weakness and fatigue on physical exertion. After normal repetitive nerve stimulation (RNS) studies performed on facial muscles, a muscle biopsy (at a median age of 9) was performed to rule out congenital myopathies. In all three cases, the biopsy findings (COX-negative fibers or respiratory chain defects) pointed to PMM. They were referred to our neuromuscular unit in adulthood to establish a genetic diagnosis. However, at this time, fatigability was evident in the physical exams and RNS in the spinal accessory nerve showed a decremental response in all cases. Targeted genetic studies revealed pathogenic variants in the <i>MUSK</i>, <i>DOK7</i>, and <i>RAPSN</i> genes. The median diagnostic delay was 29 years. Treatment resulted in functional improvement in all cases. Conclusions: Early identification of CMS is essential as medical treatment can provide clear benefits. Its diagnosis can be challenging due to phenotypic overlap with other debilitating disorders. Thus, a high index of suspicion is necessary to guide the diagnostic strategy. |
| first_indexed | 2024-03-11T04:14:26Z |
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| language | English |
| last_indexed | 2024-03-11T04:14:26Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
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| series | Journal of Clinical Medicine |
| spelling | doaj.art-b04034470d82400d8673279b1176e9762023-11-17T23:13:30ZengMDPI AGJournal of Clinical Medicine2077-03832023-05-01129330810.3390/jcm12093308Delayed Diagnosis of Congenital Myasthenic Syndromes Erroneously Interpreted as Mitochondrial MyopathiesMariana I. Muñoz-García0María Paz Guerrero-Molina1Carlos Pablo de Fuenmayor-Fernández de la Hoz2Laura Bermejo-Guerrero3Ana Arteche-López4Aurelio Hernández-Laín5Miguel A. Martín6Cristina Domínguez-González7Neuromuscular Unit, Neurology Department, Hospital Universitario 12 de Octubre, 28041 Madrid, SpainNeuromuscular Unit, Neurology Department, Hospital Universitario 12 de Octubre, 28041 Madrid, SpainNeuromuscular Unit, Neurology Department, Hospital Universitario 12 de Octubre, 28041 Madrid, SpainNeuromuscular Unit, Neurology Department, Hospital Universitario 12 de Octubre, 28041 Madrid, SpainGenetics Department, Hospital Universitario 12 de Octubre, 28041 Madrid, SpainNeuropathology Department, Hospital Universitario 12 de Octubre, 28041 Madrid, SpainGenetics Department, Hospital Universitario 12 de Octubre, 28041 Madrid, SpainNeuromuscular Unit, Neurology Department, Hospital Universitario 12 de Octubre, 28041 Madrid, SpainBackground: Congenital myasthenic syndromes (CMSs) and primary mitochondrial myopathies (PMMs) can present with ptosis, external ophthalmoplegia, and limb weakness. Methods: Our method involved the description of three cases of CMS that were initially characterized as probable PMM. Results: All patients were male and presented with ptosis and/or external ophthalmoplegia at birth, with proximal muscle weakness and fatigue on physical exertion. After normal repetitive nerve stimulation (RNS) studies performed on facial muscles, a muscle biopsy (at a median age of 9) was performed to rule out congenital myopathies. In all three cases, the biopsy findings (COX-negative fibers or respiratory chain defects) pointed to PMM. They were referred to our neuromuscular unit in adulthood to establish a genetic diagnosis. However, at this time, fatigability was evident in the physical exams and RNS in the spinal accessory nerve showed a decremental response in all cases. Targeted genetic studies revealed pathogenic variants in the <i>MUSK</i>, <i>DOK7</i>, and <i>RAPSN</i> genes. The median diagnostic delay was 29 years. Treatment resulted in functional improvement in all cases. Conclusions: Early identification of CMS is essential as medical treatment can provide clear benefits. Its diagnosis can be challenging due to phenotypic overlap with other debilitating disorders. Thus, a high index of suspicion is necessary to guide the diagnostic strategy.https://www.mdpi.com/2077-0383/12/9/3308congenital myasthenic syndromesmitochondrial myopathiesgeneticsneuromuscular disorders |
| spellingShingle | Mariana I. Muñoz-García María Paz Guerrero-Molina Carlos Pablo de Fuenmayor-Fernández de la Hoz Laura Bermejo-Guerrero Ana Arteche-López Aurelio Hernández-Laín Miguel A. Martín Cristina Domínguez-González Delayed Diagnosis of Congenital Myasthenic Syndromes Erroneously Interpreted as Mitochondrial Myopathies Journal of Clinical Medicine congenital myasthenic syndromes mitochondrial myopathies genetics neuromuscular disorders |
| title | Delayed Diagnosis of Congenital Myasthenic Syndromes Erroneously Interpreted as Mitochondrial Myopathies |
| title_full | Delayed Diagnosis of Congenital Myasthenic Syndromes Erroneously Interpreted as Mitochondrial Myopathies |
| title_fullStr | Delayed Diagnosis of Congenital Myasthenic Syndromes Erroneously Interpreted as Mitochondrial Myopathies |
| title_full_unstemmed | Delayed Diagnosis of Congenital Myasthenic Syndromes Erroneously Interpreted as Mitochondrial Myopathies |
| title_short | Delayed Diagnosis of Congenital Myasthenic Syndromes Erroneously Interpreted as Mitochondrial Myopathies |
| title_sort | delayed diagnosis of congenital myasthenic syndromes erroneously interpreted as mitochondrial myopathies |
| topic | congenital myasthenic syndromes mitochondrial myopathies genetics neuromuscular disorders |
| url | https://www.mdpi.com/2077-0383/12/9/3308 |
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