Longitudinal Insights Into Childhood Onset Facioscapulohumeral Dystrophy: A 5-Year Natural History Study.

Background And Objectives: Facioscapulohumeral dystrophy (FSHD) is an inherited muscle disorder, with childhood onset in 20% of patients. Understanding the natural history of childhood FSHD and identifying clinical and functional outcome measures are crucial for clinical care and future trials.

Methods: In a prospective nationwide FSHD cohort study (iFocus), 20 childhood-onset patients were assessed at baseline, 2 years, and 5 years. Assessments included manual muscle and functional muscle tests, FSHD clinical score (FSHD-CS), FSHD clinical severity scale (FSHD-CSS), and muscle ultrasonography (MUS).

Results: Eighteen patients (aged 2-17 years at baseline) completed the 5-year follow-up. Disease progression varied, with a mean FSHD-CS increase of 1.6. Despite objective disease progression, most participants (89%) did not perceive change. The most sensitive outcome measures were FSHD-CS (standardized response mean [SRM] 1.07), FSHD-CSS score (SRM 0.92), and MUS findings (SRM 0.68). Baseline characteristics did not predict progression.

Discussion: Disease progression was variable and often remained unnoticed by participants. Quality of life improved, and fatigue levels decreased over 5 years. The relatively slow progression and physiologic growth highlight the need for sensitive end points within a 1-2-year time frame. Future pediatric studies should consider larger international cohorts, assess reachable workspace, and include MUS and FSHD functional composite outcome measure (FSHD-COM).