Approach to Muscle and Neuromuscular Junction Disorders

PURPOSE OF REVIEW Muscle and neuromuscular junction disorders are a diverse group of disorders that can be difficult to diagnose. This article provides a diagnostic approach based on clinical history and neurologic examination leading to a narrow set of diagnostic tests.

RECENT FINDINGS Numerous discoveries in recent years have facilitated clinician access to more advanced laboratory and genetic testing to pinpoint the exact diagnosis in patients with muscle or neuromuscular junction disorders. Large-scale genetic testing has become much less expensive, and free testing has become available for many of the rare conditions because of increased research and the availability of effective therapies for these rare disorders.

SUMMARY The approach to muscle and neuromuscular junction disorders depends on the clinical pattern of muscle weakness. By classifying patients into one of 10 muscle patterns, diagnostic testing can be targeted and gene testing yield will be optimized. With the increased accessibility and reduced cost of genetic testing (eg, gene panels, whole-exome sequencing, whole-genome sequencing, and chromosomal microarray), this clinical approach to muscle weakness and targeted gene testing will ensure a cost-effective investigational plan. This clinical approach should also assist clinicians in making a timely and accurate diagnosis.

Address correspondence to Dr Mamatha Pasnoor, 3599 Rainbow Blvd, Mail Stop 2012, Kansas City, KS 66160; [email protected].

RELATIONSHIP DISCLOSURE: Dr Pasnoor has served on the advisory board of CSL Behring; as a consultant for Momenta Pharmaceuticals, Inc; and as a moderator for the University of California Irvine. Dr Pasnoor has received research/grant support from the National Institutes of Health (NIH) (R01 DK064814). Dr Dimachkie has served as a consultant or on the speaker’s bureau of Alnylam Pharmaceuticals, Inc; Audentes Therapeutics, Inc; CSL Behring; Momenta Pharmaceuticals; Nufactor; RMS Medical Products; Sanofi Genzyme; Takeda; and Terumo Medical Company. Dr Dimachkie has received grants from Alexion Pharmaceuticals, Inc; Alnylam Pharmaceuticals, Inc; Amicus Therapeutics, Inc; BioMarin; Bristol-Myers Squibb Company; Catalyst Pharma; CSL Behring; Genentech, Inc; GlaxoSmithKline plc; Grifols, SA; the Muscular Dystrophy Association; The Myositis Association; the National Institutes of Health; Novartis AG; Sanofi Genzyme; Octapharma; Orphazyme; UCB, Inc; the US Food and Drug Administration/Orphan Products Development; and ViroMed Laboratories.

UNLABELED USE OF PRODUCTS/INVESTIGATIONAL USE DISCLOSURE: Drs Pasnoor and Dimachkie report no disclosures.