Background: Advancing newborn screening (NBS) for Duchenne muscular dystrophy (DMD) requires evidence of benefit of early diagnosis and intervention. DMD NBS enables initiation of therapies early in disease course. However, slow disease progression and rarity of identifying babies make demonstrating the benefit of early treatment initiation difficult. Sibling case reports demonstrating early diagnosis and treatment initiation can be used as a proxy.
Methods: PPMD’s Certified Duchenne Care Centers were invited to submit case reports of siblings with DMD that demonstrated benefits of early diagnosis (N=2).
Results: Cohort 1: Sibling 1A was diagnosed at 7 years, sibling 1B at 1.5 months. 1A initiated corticosteroids at 8 years; 1B initiated at 5.4 years. At age 8, the older sib had a full Gowers, abnormal walking/running, frequent falls, and no hopping or jumping. 1B enrolled in a clinical trial at age 4 and is now 7 years and doing well clinically, including playing soccer with fatigue modifications. Cohort 2: Sibling 2A was diagnosed at 3 years versus 2B at 4 months. 2A initiated eteplirsen at 3 years, corticosteroids at 4 years, transitioned to viltolarsen at age 6, and remains on those therapies. 2B initiated eteplirsen at 10 months, transitioned to viltolarsen at age 3, and added corticosteroids at age 4. Functional testing of 2B is more challenging due to cognitive deficits not present in 1B– both are doing well clinically with minimal functional impairments.
Discussion: Early diagnosis enables early initiation of therapies and increased opportunities for clinical trial participation, which is demonstrated in the sibling cohorts. Comparison of outcomes is complicated by age differences, slow progression of disease, long time course of interventions required, variability in expression within a sibship, and functional outcome issues, including the need for participant cooperation. Studies following early diagnosed children are needed to provide additional evidence of benefit.