P253 Motor function and genotype-phenotype correlations in paediatric Becker muscular dystrophy

The few available adult-focused studies in Becker muscular dystrophy (BMD) have demonstrated variable clinical severity in genotype subgroups, e.g., “mild” group for exon deletions that end at exon 51 (x-51) and “severe” groups for deletions that begin at exon 45 (45-x) and mutations in domain 1(promoter through exon 9). Better delineation of motor function in paediatric BMD can inform clinical consultation and trial design. Our study aims to characterize the motor function and genotype-phenotype correlations in paediatric BMD. This is a retrospective study of electronic health records of 86 individuals with paediatric BMD with encounters from 7/1/2008 to 4/30/2022. Data collected include demographics, genetic testing and motor function measures: North Star Ambulatory Assessment (NSAA), 10-meter walk/run, 4-stair climb and Gowers’ maneuver. Data were analysed via multiple linear regression and repeated measures model. “Severe” BMD, identified as ever demonstrating full Gowers’ sign or ever on steroids, performed worse in all motor function measures. The earliest significant difference was shown in the 4-stair ascent and 10-meter walk/run at age 8 years for those identified by full Gowers’ sign, and in the 4-stair climb ascent and descent at age 10 for those ever on steroids. The group with 45-x deletions and mutations involving domain 1 performed worse than the rest of cohort in all measures, with the earliest significant difference seen in 4-stair climb at age 9. Those with deletions x-51 demonstrated better performance in the 10-meter walk/run and NSAA when compared against the deletion 45-x and domain 1 group. A subgroup of “severe” BMD differed from the rest at as early as age 8 years. Consistent with previous adult data, those with 45-x deletion and domain 1 mutations had worse motor function. X-51 deletion had a milder motor phenotype. The 4-stair climb ascent is the most consistently identified measure showed difference at the earliest age. The few available adult-focused studies in Becker muscular dystrophy (BMD) have demonstrated variable clinical severity in genotype subgroups, e.g., “mild” group for exon deletions that end at exon 51 (x-51) and “severe” groups for deletions that begin at exon 45 (45-x) and mutations in domain 1(promoter through exon 9). Better delineation of motor function in paediatric BMD can inform clinical consultation and trial design. Our study aims to characterize the motor function and genotype-phenotype correlations in paediatric BMD. This is a retrospective study of electronic health records of 86 individuals with paediatric BMD with encounters from 7/1/2008 to 4/30/2022. Data collected include demographics, genetic testing and motor function measures: North Star Ambulatory Assessment (NSAA), 10-meter walk/run, 4-stair climb and Gowers’ maneuver. Data were analysed via multiple linear regression and repeated measures model. “Severe” BMD, identified as ever demonstrating full Gowers’ sign or ever on steroids, performed worse in all motor function measures. The earliest significant difference was shown in the 4-stair ascent and 10-meter walk/run at age 8 years for those identified by full Gowers’ sign, and in the 4-stair climb ascent and descent at age 10 for those ever on steroids. The group with 45-x deletions and mutations involving domain 1 performed worse than the rest of cohort in all measures, with the earliest significant difference seen in 4-stair climb at age 9. Those with deletions x-51 demonstrated better performance in the 10-meter walk/run and NSAA when compared against the deletion 45-x and domain 1 group. A subgroup of “severe” BMD differed from the rest at as early as age 8 years. Consistent with previous adult data, those with 45-x deletion and domain 1 mutations had worse motor function. X-51 deletion had a milder motor phenotype. The 4-stair climb ascent is the most consistently identified measure showed difference at the earliest age.