ObjectiveOur goal was to perform a systematic review of the literature to demonstrate the prevalence of cardiac abnormalities identified using cardiac investigations in patients with mitochondrial myopathy (MM).MethodsThis systematic review surveys the available evidence for cardiac investigations in MM from a total of 21 studies including 825 participants. Data were stratified by genetic mutation and clinical syndrome.ResultsWe identified echocardiogram and ECG as the principal screening modalities that identify cardiac structural (29%) and conduction abnormalities (39%) in various MM syndromes. ECG abnormalities were more prevalent in patients with m.3243A>G mutations than other gene defects, and patients with mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) had a higher prevalence of ECG abnormalities than patients with other clinical syndromes. Echocardiogram abnormalities were significantly more prevalent in patients with m.3243A>G or m.8344A>G mutations compared with other genetic mutations. Similarly, MELAS and MERRF had a higher prevalence compared with other syndromes. We observed a descriptive finding of an increased prevalence of ECG abnormalities in pediatric patients compared with adults.ConclusionsThis analysis supports the presence of a more severe cardiac phenotype in MELAS and myoclonic epilepsy with ragged red fibres syndromes and with their commonly associated genetic mutations (m.3243A>G and m.8344A>G). This provides the first evidence basis on which to provide more intensive cardiac screening for patients with certain clinical syndromes and genetic mutations. However, the data are based on a small number of studies. We recommend further studies of natural history, therapeutic response, pediatric participants, and cardiac MRI as areas for future investigation.

Hereditary spastic paraplegias (HSPs) are a diverse group of genetic conditions with variable severity and onset age. From a neurogenetic clinic, we identified 14 patients with very late-onset HSP, with symptoms starting after the age of 35. In this cohort, sequencing of known genetic causes was performed using clinically available HSP sequencing panels. We identified 4 patients with mutations in SPG7 and 3 patients with SPAST mutations, representing 50% of the cohort and indicating a very high diagnostic yield. In the SPG7 group, we identified novel variants in two patients. We have also identified two novel mutations in the SPAST group. We present sequencing data from cDNA and RT-qPCR to support the pathogenicity of these variants, and provide observations regarding the poor genotypephenotype correlation in these conditions that should be the subject of future study. ARTICLE HISTORY

Background: Cardiac dysfunction has significant impact on morbidity and mortality in patients with mitochondrial disorders. Cardiac screening tests are generally recommended because cardiac dysfunction can occur at any point in the disease course, and is amenable to treatment. However there is no clear evidence indicating the best screening strategy in patients with mitochondrial myopathy. Methods: Systematic review of the literature for cardiac investigations in adult patients with mitochondrial myopathy. We considered 1303 relevant abstracts, from which 58 full-length articles were reviewed. Seventeen articles including 701 total participants met inclusion criteria. Data extracted included age, diagnosis, and results from ECG, echocardiogram, cardiac MRI, nuclear medicine studies, and Holter monitor. Results: We identified echocardiogram and ECG as the principal screening modalities, that identify cardiac structural (26%) and conduction abnormalities (37%) in patients from various mitochondrial myopathy syndromes. Holter monitor was not a high yield investigation and limited studies were identified using cardiac MRI or nuclear medicine. Conclusions: We recommend screening with ECG and echocardiogram every 1-2 years in MERRF/MELAS, and every 3-5 years in milder syndromes when cardiac symptoms are not present. Only five of the included studies provided any follow-up data. We recommend studies of natural history, therapeutic response, and of cardiac MRI as areas for future study.