(Scientific Session) Secondary Neuromuscular Disorders in Patients with Duchenne Muscular Dystrophy

Background and/or Objectives: Duchenne’s Muscular Dystrophy (DMD) is a genetic disorder that leads to significant physical impairment and a high risk for cardiomyopathy in children. Treatments for DMD are specific to each patient’s genetics and are rather expensive, costing some patients over a million dollars per year. We hypothesized that some patients with DMD may have a secondary neuromuscular (NM) disorder that could skew data during pharmaceutical clinical trials and lead to incomplete treatment plans.

Objectives: Discover how common it is for patients with DMD to have a secondary NM disorder using a new genetic panel and to recognize this panel's positive yield.

Design: This study is a retrospective review of all patients tested with the Invitae comprehensive neuromuscular disorders panel ordered by two pediatric neurologists from June 27, 2019 – June 29, 2022.

Setting: Hospital

Participants: Children suspected to have neuromuscular disease.

Interventions: Genetic Panel

Main Outcome Measures: Pathological DMD genetic variants and other neuromuscular disease variants.

Results: Three hundred fifty-three (353) panels were reviewed. One hundred twenty-six (126) revealed a pathological variant in a neuromuscular gene giving the panel a positive yield of 35.7%. Thirty-two (32) patients with DMD were identified. Three (3) of these DMD patients, 9.4%, were found to have at least one secondary NM disorder. Disorders were found in genes TTN, NEB, GAA, and CLCN1 which are associated with a spectrum of neuromuscular disorders.

Conclusions: Titinopathies (TTN) and Pompe disease (GAA) can cause progressive cardiomyopathies. Some of these disorders have treatments. Pompe (GAA) is potentially amenable to enzyme replacement therapy while CLCN1 is treatable with sodium channel agents. Secondary neuromuscular disorders should be considered in patients with DMD before deciding on a treatment plan. Failure to recognize these other disorders would result in unexpected treatment failures that could sideline potentially useful medications in a trial setting or result in expensive treatment failures when used commercially.