The Natural History of Pediatric Becker Muscular Dystrophy: A Single Center Retrospective Cohort Study with Muscle Ultrasound Characterization


Clinical Management

Poster Number: T303


Cara Piccoli, MD, Stanford University Medical Center, Allan Glanzman, PT, DPT, PCS, Children’s Hospital of Philadelphia, Brianna Gross, MS,LCGC, Children's Hospital of Philadelphia, Sabrina Yum, M.D., Children's Hospital of Philadelphia

Becker Muscular Dystrophy (BMD) is a common degenerative myopathy, but there is little data on the natural history in pediatric patients. BMD phenotype is heterogenous and can include non-motor symptoms. BMD is differentiated from Duchenne Muscular Dystrophy by loss of ambulation >12 years of age. Muscle ultrasound (MUS) is a promising bedside test for myopathies, but its characteristics in BMD are unknown. The goal of this study was to use the largest pediatric cohort to date to characterize the natural history of childhood-onset BMD.

Study Design
This was a retrospective chart review of patients at the Children’s Hospital of Philadelphia between 2010-2022. Males with genetically- or immunohistochemically-confirmed BMD before 18 years of age were included. Demographics, genotype, symptoms, and biomarkers were recorded. A composite functional severity score (FSS) was created based on examination at each visit. Qualitative MUS data was graded according to the Heckmatt score.

Seventy patients (45 of them >12 years of age) were included. Forty-four pathogenic variants were identified. Incidental hyperCKemia was the most common reason for referral (N=18). Average age of symptom onset was 5.5±3.5 years. At final follow-up, 40 patients had no-mild and 25 patients had moderate-severe functional impairment. Three patients became non-ambulatory (average age 16.3±2.5 years). Worse FSS was associated with frameshift mutations (p=0.0002), cardiomyopathy (p=0.01), and older age (p=0.04). Contractures and cognitive differences were the most common comorbidities. Additional analyses were done based on genotype and demographics. Higher average Heckmatt scores were seen in patients with moderate-severe than no-mild functional impairment (p=0.037). The rectus femoris and vastus lateralis were the most abnormal muscles.

Our data expanded the knowledge of the natural history of pediatric BMD. We confirmed the heterogenicity of disease severity and rate of progression. We demonstrated that more than half of the patients have no or only mild weakness, which is much higher percentage than previously reported. This information will help inform the design of clinical trials for BMD. We also proposed a clinical severity scale that could be widely implemented without extensive training required. Muscle ultrasound change correlated with severity of disease and may service as a biomarker for disease progression and response to therapy.