Abstract
Ocular myopathy, typically manifesting as progressive external ophthalmoplegia (PEO), is among the most common mitochondrial phenotypes. The purpose of this study is to better define the clinical phenotypes associated with ocular myopathy. This is a retrospective study on a large cohort from the database of the “Nation-wide Italian Collaborative Network of Mitochondrial Diseases”. We distinguished patients with ocular myopathy as part of a multisystem mitochondrial encephalomyopathy (PEO-encephalomyopathy), and then PEO with isolated ocular myopathy from PEO-plus when PEO was associated with additional features of multisystemic involvement. Ocular myopathy was the most common feature in our cohort of mitochondrial patients. Among the 722 patients with a definite genetic diagnosis, ocular myopathy was observed in 399 subjects (55.3%) and was positively associated with mtDNA single deletions and POLG mutations. Ocular myopathy as manifestation of a multisystem mitochondrial encephalomyopathy (PEO-encephalomyopathy, n = 131) was linked to the m.3243A>G mutation, whereas the other “PEO” patients (n = 268) were associated with mtDNA single deletion and Twinkle mutations. Increased lactate was associated with central neurological involvement. We then defined, among the PEO group, as “pure PEO” the patients with isolated ocular myopathy and “PEO-plus” those with ocular myopathy and other features of neuromuscular and multisystem involvement, excluding central nervous system. The male proportion was significantly lower in pure PEO than PEO-plus. This study reinforces the need for research on the role of gender in mitochondrial diseases. The phenotype definitions here revisited may contribute to a more homogeneous patient categorization, useful in future studies and clinical trials.
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Acknowledgements
This work was supported by Telethon (Grant numbers GUP09004 and GSP16001). The patients’ association MITOCON provided the web-platform assistance, partially supported this work and supports the work of Elena Caldarazzo Ienco.
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The authors declare no conflicts of interest, except Dr Mancuso, involved in Stealth Peptides clinical trial on mitochondrial myopathies, and Dr Carelli who is involved in clinical trials on LHON with Santhera Pharmaceuticals, GenSight, Edison Pharmaceuticals, and on mitochondrial myopathy with Stealth Peptides.
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The study been approved by the appropriate ethics committee and has been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. All persons gave their informed consent prior to their inclusion in the study.
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Orsucci, D., Angelini, C., Bertini, E. et al. Revisiting mitochondrial ocular myopathies: a study from the Italian Network. J Neurol 264, 1777–1784 (2017). https://doi.org/10.1007/s00415-017-8567-z
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DOI: https://doi.org/10.1007/s00415-017-8567-z