Molecular and neurological features of MELAS syndrome in paediatric patients: A case series and review of the literature.

BACKGROUND: Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome is one of the most well-known mitochondrial diseases, with most cases attributed to m.3243A>G. MELAS syndrome patients typically present in the first two decades of life with a broad, multi-systemic phenotype that predominantly features neurological manifestations--stroke-like episodes. However, marked phenotypic variability has been observed among paediatric patients, creating a clinical challenge and delaying diagnoses. METHODS: A literature review of paediatric MELAS syndrome patients and a retrospective analysis in a UK tertiary paediatric neurology centre were performed. RESULTS: Three children were included in this case series. All patients presented with seizures and had MRI changes not confined to a single vascular territory. Blood heteroplasmy varied considerably, and one patient required a muscle biopsy. Based on a literature review of 114 patients, the mean age of presentation is 8.1 years and seizures are the most prevalent manifestation of stroke-like episodes. Heteroplasmy is higher in a tissue other than blood in most cases. CONCLUSION: The threshold for investigating MELAS syndrome in children with suspicious neurological symptoms should be low. If blood m.3243A>G analysis is negative, yet clinical suspicion remains high, invasive testing or further interrogation of the mitochondrial genome should be considered.

A Systematic Review of Utilisation of Diurnal Timing Information in Clinical Trial Design for Long QT Syndrome.

Diurnal oscillations in human cardiac electrophysiology are thought to be under the control of the endogenous circadian clock. The incidence of arrhythmic events in patients with Long QT syndrome (LQTS) varies diurnally. The diurnal variation in QT interval has previously been identified as a potential for error in clinical trials which utilise ECG measurement. We performed a systematic review of clinical trials for LQTS to identify practice around specification of timing information for point electrocardiogram (ECG) measurements, analysis of continual ECG recordings ≥24 h, and drug delivery. Despite guidelines having been issued around the analysis of 24-h ECG recordings, we identify a lack of usage of detailed time of day information in trial design for LQTS studies, which has the potential to affect the interpretation of the results of drug trials. We identify that, in contrast, clinical trials for QT prolonging drugs demonstrate increased incorporation of time of day information of both QT analysis and drug dosing. We provide a visual portal to allow trial designers and clinicians to better understand timing of common cardiac-targeting drugs, and to bear this concept in mind in the design of future clinical trials.

Horizon Scanning in Cancer Genomics: How Advances in Genomic Medicine Will Change Cancer Care Over the Next Decade.

PURPOSE OF REVIEW: Advances in genomic medicine have the potential to revolutionise cancer patient care by driving forwards the clinical practice of precision oncology. This review aims to outline how genomic medicine advances may alter the care of cancer patients and their families over the next 10 years. RECENT FINDINGS: The translation of oncogenomic advances into the clinical environment will likely be facilitated by the increasing availability of next-generation sequencing technologies and the increasing genomic literacy of healthcare professionals. The implementation of the centralised, nationwide NHS Genomic Medicine Service promises to improve equity of cancer care and to facilitate personalisation of almost every stage of the care pathway, from informing population screening and how we diagnose cancer to delivering prognoses and surveillance. Advances in cancer pharmacogenomics, and other "omics" technologies, have a tremendous potential to optimise patient care. Genomic medicine advances will also enhance the care offered to cancer patients' families. SUMMARY: Genomic medicine advances are likely to transform almost every aspect of a cancer patient's care pathway. Cancer care will profoundly improve over the next decade, increasing UK cancer survival rates and improving patient outcomes.