G.P.13: Baseline characteristics of the CINRG infantile facioscapulohumeral muscular dystrophy (FSHD) cohort

Abstract

Infantile FSHD is uncommon. We aim to describe the clinical features and secondary conditions in early onset FSHD. This study was conducted at participating Cooperative International Neuromuscular Research Group (CINRG) sites. The diagnosis was based on onset of symptoms involving the facial or shoulder girdle muscles and contraction of the D4Z4 repeat array (<38kb) in the 4q35 subtelomeric region. In addition, participants were identified based on onset of facial and shoulder weakness <10years of age. Clinical assessments included cognitive, hearing, eye, speech, and motor function evaluations. Descriptive statistics were used to summarize the baseline characteristics. Spearman correlation was used to determine the association between EcoR1 fragment size and degree of muscle involvement. To date, 20 participants (10 males and 10 females, median age=16.7 (IQR 13.1–25.4) years) were recruited. The median EcoR1 fragment size was 15 (IQR 12–18.5) kb. 12/16 (75%) had <4 D4Z4 repeats and 8 (50%) had no family history of FSHD. The median age at onset of facial and shoulder weakness was 4 (IQR 1–6) and 7 (IQR 5–8) years respectively. Four (24%) participants were dependent on wheelchair for all mobility, 6 (46%) had noticeable speech impairment, and 15 (88%) had moderate to severe facial and scapular weakness. Extramuscular manifestations included 1 (6%) with intellectual disability, 3 (17%) with visual concerns, 4 (24%) with developmental delay, 6 (38%) with hearing loss, and 9 (53%) with chronic pain. The EcoR1 fragment size had a strong negative correlation with Brooke scale (<i>r</i>=−0.80), Vignos scale (<i>r</i>=−0.67), and FSHD clinical severity scale (<i>r</i>=−0.72 for facial, −0.64 for shoulder, and −0.60 for pelvic muscle weakness). Infantile FSHD causes severe weakness and early loss of independent ambulation. Smaller EcoR1 fragment size was associated with great disease severity. Additional longitudinal studies will help determine the rate of decline in motor function over time.