Science News: Clinical and Genetic Characteristics in Young, Glucocorticoid-Naïve Boys With Duchenne Muscular Dystrophy

Submitted by: Milvia Y. Pleitez, MD
Edited by: Niranjan Singh, MD

Schiava M, Amos R, VanRuiten H, et al. Clinical and genetic characteristics in young, glucocorticoid-naive boys with Duchenne muscular dystrophy. Neurology, 98(4), e390–e401. Advance online publication. https://doi.org/10.1212/WNL.0000000000013122

Summary: This article reports the genotype-phenotype characteristics of the largest international cohort of Duchenne muscular dystrophy (DMD) boys (participants in the Finding the Optimum Corticosteroid Regime for Duchenne Muscular Dystrophy (FOR-DMD)) pretreated with glucocorticoids. Out of 196 boys recruited, 193 were found to have a DMD mutation.
 
Various characteristics reported in the cohort included age, weight, height, body mass index (BMI), time to walk/run, North Star Ambulatory Assessment (NSAA) score, 6 minute walk test (MWT) distance, time to rise and forced vital capacity (FVC). Additionally, genotypes, family history, mother carrier state, means of diagnosis, phenotypes and genotype-phenotype associations were reported.
 
Key findings included that the most common mutations were out of frame deletions (67.4%) followed by various small mutations (19.6%), duplications (11%), and in-frame deletions 2%. The most common out of frame deletions were exon skipping with exon 51 skipping being the most frequent.
 
Carrier status of mother documented in 66.3% of enrolled boys with positive confirmation of carrier status in mother in 63.8% of these.
 
Mean age of parental concern was 2.5 years, genetic diagnosis mean age was 4.5 years and mean diagnostic delay was 2.2 years.
 
Motor milestone data was recorded in 98.9% of boys. Age of independent walking was 17.1 +/-4.2 months. At the time of diagnosis, elevated creatine kinase (CK) levels were noted in 95.6% (173/181), weakness was noted in 78.7% (140/178), and calf hypertrophy and Gower’s reported in 74.1%. Additional clinical features reported included waddling gait, contractures, lumbar hyperlordosis and large bone fractures.
 
Anthropometric measures were reported, and key findings included the finding that all boys were below the 50% percentile for height, and all were below the 75% percentile for weight.
 
Mutation types did not influence CK level, mean age at independent walking or functional outcomes.
 
Knowing the pre-glucocorticoid state in DMD boys may help us understand outcome measures and eligibility criteria for research trials.
 
Comments: While there has been much written about genotype-phenotype associations in DMD boys treated with glucocorticoids, little has been written about steroid naive DMD boys. This landmark article has confirmed some data that was already suspected. Additionally, it has collected data that is key to earlier diagnosis, data that needs to be considered when recommending glucocorticoids and data relevant to future research studies.