The advent of next generation sequencing (NGS) and its application to clinical practice will have a huge impact on our approach to the diagnosis of inherited myopathies. Exome sequencing will be much quicker and cheaper than our past practice of sequencing candidate genes one by one …however the reality is that genome-wide sequencing of individual families will yield a tsunami of genetic variants in multiple different genes that need to be tested and validated as the possible disease-causing mutations. This will be particularly true for large and repetitive genes such as nebulin, titin and RYR1.

A number of additional factors complicate reaching a specific genetic diagnosis for congenital myopathies. The relationship between each congenital myopathy, defined on histological grounds, and the genetic cause is complex. Most congenital myopathies can be caused by mutations in more than one gene and many of the causative genes are associated with more than one histological diagnosis. In addition, the histological abnormalities on biopsy can evolve and a patient’s diagnosis may therefore change over time if re-biopsied. Thus detailed clinical evaluation, identification of specific diagnostic clinical clues and ancillary investigations such as muscle imaging, in addition to muscle biopsy findings, play an increasingly important role in prioritising gene testing and in reaching a final genetic diagnosis. Over the past two years, there has been an international effort supported by Foundation for Strength, TREAT-NMD and ENMC to develop expert guidelines the Diagnosis Congenital Myopathies.

In this presentation, Professor Kathryn North will review of recent advances in the diagnosis of congenital myopathies, and the clinical clues that aid the clinician in reaching a specific genetic diagnosis.

Speaker:Professor Kathryn North is a paediatric neurologist and clinical geneticist. She recently relocated from Sydney to Melbourne to take up directorship of the Murdoch Childrens Research Institute. She is also the David Danks Professor of Child Health Research at the University of Melbourne. Her laboratory research interests focus on the molecular basis of inherited muscle disorders – particularly the muscular dystrophies and congenital myopathies – as well as genes which influence normal skeletal muscle function and elite athletic performance. Her clinical research focuses on clinical trials of therapies for muscular dystrophy as well as the development of interventions for children with learning disabilities. Kathryn has received numerous awards for her research in neuromuscular and neurogenetic disorders, including the Ramaciotti Medal for Excellence in Biomedical Research and the Member of the Order of Australia (AM) in 2012.