New diagnostic and therapeutic modalities in neuromuscular disorders in children.

Abstract

Pediatric neuromuscular disorders are a diverse group of conditions that affect how muscle and nerve function. They involve the motor neurons, nerves, neuromuscular junction and muscles. Pathology of any of these regions leads to the inability to perform voluntary movements. Over time, the natural progression of most of these disorders is followed by significant disability, and at the most extreme, almost complete paralysis and death secondary to complications. Diagnostic measures for pediatric neuromuscular disorders, like that of most medical conditions, relies heavily on clinical presentation, history and a detailed physical examination. Primary additional diagnostic measures have included serum creatine kinase (CK) levels, electromyography (EMG), nerve conduction studies (NCS) and muscle or nerve biopsies, which has historically been the gold standard. In the last several decades less invasive testing has become more common such as muscle magnetic resonance imaging (MRI) and genetic testing.\xa0 The advances of molecular genetics, such as next generation sequencing (NGS) which includes whole-exome sequencing (WES) and whole-genome sequencing (WGS), enable clinicians to pinpoint more accurately exact gene mutations. The advent of genetic testing enhances personalized medicine. The field of pediatric neuromuscular disorders is also undergoing a remarkable evolution in therapeutic modalities including novel targeted therapies such as exon skipping/inclusion and gene replacement therapies. This is a review of the initial approach to suspected neuromuscular disorders in children as well as up to date diagnostic and therapeutic modalities for the most common pediatric neuromuscular disorders. As the world enters the new decade, there are encouraging therapeutic results. However, there remain key challenges to these modalities including limitations in its applicability, optimization for delivery of gene replacement therapies and in its effectiveness.