Assessing infants & toddlers with neuromuscular disorders under 5 years of age using the Neuromuscular Gross Motor Outcome (GRO)

Topic:

Translational Research

Poster Number: S53

Author(s):

Megan Iammarino, DPT, Nationwide Children's Hospital, Natalie Reash, PT, DPT, Nationwide Children's Hospital, Lindsay Pietruszewski, DPT, Abigail Wexner Research Institute at Nationwide Children's Hospital, Melissa Smith, DPT, Abigail Wexner Research Institute at Nationwide Children's Hospital, Christopher Steiner, DPT, Abigail Wexner Research Institute at Nationwide Children's Hospital, Jenna Lammers, PT, MSR, PCS, NCS, CNT, Powell Gene Therapy Center, Lauren Humphrey, Abigail Wexner Research Institute at Nationwide Children's Hospital, Audrey Beale, Abigail Wexner Research Institute at Nationwide Children's Hospital, Megan A. Waldrop, MD, Nationwide Children's Hospital and Ohio State University Wexner Medical Center, Chang-Yong Tsao, MD, Abigail Wexner Research Institute at Nationwide Children's Hospital, Shannon Chagat, NP, Abigail Wexner Research Institute at Nationwide Children's Hospital, Eleonora D'Ambrosio, MD, Abigail Wexner Research Institute at Nationwide Children's Hospital, Stefan Nicolau, MD, Nationwide Children's Hospital, Alayne Meyer, MS, LGC, Abigail Wexner Research Institute at Nationwide Children's Hospital, Kevin Flanigan, MD, Nationwide Children's Hospital, Anne M. Connolly, MD, Nationwide Children’s Hospital, The Ohio State University College of Medicine, Jerry Mendell, MD, Abigail Wexner Research Institute at Nationwide Children's Hospital, Linda Lowes, PT, PhD, Nationwide Children's Hospital, Lindsay Alfano, DPT, Nationwide Children's Hospital

Background: Infants and toddlers with neuromuscular disorders (NMD) are being treated at younger ages as increasing numbers of disease-modifying therapies receive commercial approval; these numbers may further increase with ongoing initiatives to include these treatable-disorders to state-regulated newborn screening (NBS) panels. Similarly, clinical trials are moving into younger cohorts as they demonstrate greater potential to benefit from possible treatments. The standardized evaluation of motor function can be difficult in children under 5 years of age, and previously validated disease-specific outcomes may have limited utility once individuals surpass previous functional expectations. Further, standardized developmental assessments are not tailored to individuals with neuromuscular disease and scoring rules frequently assign credit to motor skills not yet achieved, based on the age at time of assessment.
Objectives: To evaluate motor development and function in children < or = to 5 years of age using the Neuromuscular Gross Motor Outcome (GRO), in addition to a common battery of clinical outcomes, during regularly scheduled standard of care appointments at Nationwide Children’s Hospital and University of Florida clinics. The GRO is a 50-item assessment developed to quantify motor function across the developmental and disease spectrum in individuals with neuromuscular disorders. Results: One hundred ninety-seven children < or = to 5 years of age (range 0.1 – 4.9 yrs) were evaluated. Childhood diagnoses include Duchenne muscular dystrophy (DMD) [n=55], spinal muscular atrophy (SMA) [n=68], and others with either genetically confirmed NMD, global delay, or non-NM genetic disorders [n=74]. Fifty-eight subjects had at least one additional visit, for a total of 311 visits. Average trajectories of performance by sub-group cohort will be presented. The GRO quantified motor function in patients as young as 7 days (referred via NBS) through 5 years with varied abilities on major motor milestones such as rolling, sitting, crawling, standing, and higher-level developmental skills that included walking, jumping, and running. In the SMA cohort, 58% of infants were unable to be assessed validly by any other NMD-specific measure. Conclusions: GRO provides a standardized and consistent measure of motor function especially for clinical trials inclusive of participants < 5 years of age, as this group has become the predominant target for developing new therapies.