364P Gross motor delays in boys with Duchenne muscular dystrophy are seen in infancy

Abstract

There is an increased focus on the developmental abilities of infants and young boys with Duchenne Muscular Dystrophy as clinical trials are increasingly enrolling younger cohorts. Normal maturational gains in gross motor skills, however, makes clinical trials challenging as it is difficult to determine if post-treatment improvement is attributable to the therapeutic or simply to maturation. While there is some understanding of the natural history of infants and toddlers with DMD, there is an urgent need to objectively quantify motor function in this young cohort using a normative-referenced scale to enable data-driven decision-making in these early years. Several countries have now implemented newborn screening for DMD which will allow for diagnosis within the first few weeks of life. Families will likely have questions about trial participation or initiating approved therapies. This submission reports on the prevalence of gross motor delay and documents the trajectory of gross motor skill acquisition in boys with Duchenne muscular dystrophy using the Bayley Scales of Infant & Toddler Development, Third Edition (Bayley 3). Ninety boys (2 months – 5.8 years at their first visit) were evaluated during regularly scheduled clinic visits. Deletion was the most common genetic variant (69%), but the sample included duplications, nonsense, splice site and INDEL variants. We report on longitudinal assessments for 47 boys, with two to six follow up visits, resulting in 128 total assessments. All boys had a delay in gross motor skills when compared with normative controls at least one visit. Although the Bayley 3 was designed for use in children under the age of 42.5 months, none of the older boys in this cohort achieved a perfect score suggesting it could be used until age 6 years. Raw scores increased with age; however, a plateau was noted at 5 years. The average scaled score (which compares a boy's performance to age matched peers; mean=10; SD= 3) was 5 which indicates a significant delay and is 1.6 standard deviations below the mean. Five out of the 90 boys (5.5%) received a scaled score within the normal range at one visit, but this was not maintained over time. The minimum detectable change for this cohort was 4.8 raw points and 1.01 scaled points. Interestingly, there were several items that presented more difficulty than would be expected for their age. These included jumping forward, jumping down from a step, heel-toe walking, standing on one foot for 8 seconds and using a reciprocal pattern to climb stairs. With newborn screening and interventional trials recruiting younger cohorts it is imperative that we understand the typical developmental trajectory of infants and young boys with DMD. A well-documented developmental natural history study could be used to determine if the rate of change in gross motor development following an intervention falls outside of expectations for DMD.