G.P.2: Clinical profile of pediatric patients with Becker Muscular Dystrophy (BMD)

Abstract

Antisense oligonucleotide (AON)-induced exon skipping in Duchenne muscular dystrophy (DMD) patients aim to restore out of frame dystrophin gene mutations to in-frame mutations with resultant dystrophin production and a BMD phenotype. BMD occurs in 1 in 20000 males and is associated with partially functional truncated dystrophin protein. Pending on the amount of truncated dystrophin, the clinical phenotype of BMD patients vary from those with loss of ambulation in the mid-teens to patients with normal skeletal motor function in late adulthood. Natural history data of pediatric BMD patients would provide useful clinical information regarding the potential endpoints of therapeutic efficacy of exon skipping treatment trials. To characterize the clinical profile of pediatric patients with Becker Muscular Dystrophy (BMD) IRB approved retrospective case series' review of BMD patients Clinical profiles of BMD patients: 48 males with clinical and genetic/or histologic diagnosis of Becker's Muscular Dystrophy. Patient characteristics: Mean age at diagnosis – 5.4years (0.75–12years); mean CK at time of diagnosis – 8036 (161–40,000); Presenting symptom(s) – elevated LFTs (10/48), gross motor delay (9/48), hypotonia (6/48), exercise intolerance/myalgias (15/48), abnormal walking/running gait (17/48), family history (6/48), incidental lab finding (9/48), fatigue (1/48); Indices of muscle mass: Pelvic/thigh Muscle MRI – (<i>n</i>=33) normal study to trace fatty infiltration – 16, mild-to-moderate fatty infiltration – 11, diffuse/significant – 6; mean serum creatinine – 0.41 (0.1–0.8); DEXA mean % lean muscle mass – 70 (51–82); Bone health: mean DEXA distal femur R1 <i>z</i>-score – 0.75 (2.7–3.8); Cardiac function: mean left ventricular ejection fraction (%) – 63 (50–77); Motor status at last follow-up – normal function – 24, stable, near-normal function – 19, stable, abnormal function – 2, decline in motor function – 1, lost to follow-up – 2.