Introduction
Congenital muscle diseases have a diverse array of clinical, genetic and histopathologic features (1). Although past cohorts have described features of these disease (2), there remains a gap in knowledge regarding outcomes. In this study, we aim to describe a large cohort of congenital myopathy patients and delineate features associated with invasive ventilation dependence.
Methods
This is a retrospective chart review of patients seen in the Children’s Health Neuromuscular Disorders clinic in the last 15 years with a diagnosis of a congenital myopathy / muscular dystrophy. Data collected included genetics, muscle pathology, electrophysiology and clinical history. Statistical methods included Fisher’s exact test, Kruskal-Wallis test, and Bonferroni correction for multiple comparisons.
Results
161 patients were included in the study (58% male, 42% female). The median age at time of data collection was 181 months and 18/161 patients were deceased (median age 43 months [95% CI 3.7-87]). The most common genetic variants were in RYR1 (n=29), MTM1 (n=16), TTN (n=15), LAMA2 (n=14), DMPK (n=13), NEB (n=12). Common specific muscle pathology patterns were centronuclear (n=18), central core (n=11), multiminicore (n=10) and nemaline rods (n=10). 91 (56%) patients required no or only non-invasive respiratory support, whereas 32 (20%) required invasive ventilation. A third group of 38 patients (24%) required invasive ventilation in the past but later weaned off support. Factors that significantly differed between the three groups were facial muscle weakness, oropharyngeal dysphagia, wheelchair dependence, deceased at time of study, age at diagnosis, hospitalizations in first year of life. Muscle biopsy patterns, genetic etiology, CK level, EMG/NCS findings, cardiomyopathy, ethnicity, sex, socioeconomic status did not correlate significantly with ventilation status.
Conclusion
Facial weakness, dysphagia, early onset, and wheelchair dependence were associated with invasive ventilation dependence. Further natural history studies are needed to better understand these diverse disorders and assess clinical trial readiness.
References
1. North KN, Wang CH, Clarke N, et al. Approach to the diagnosis of congenital myopathies. Neuromuscul Disord. 2014 Feb;24(2):97–116.
2. Natera-de Benito D, Ortez C, Jou C, et al. The Phenotype and Genotype of Congenital Myopathies Based on a Large Pediatric Cohort. Pediatr Neurol. 2021;115:50-65.