Background: Facioscapulohumeral muscular dystrophy (FSHD) is a rare, relentlessly progressive neuromuscular disorder associated with muscle weakness, functional impairment, and reduced quality of life. While clinical features of FSHD are increasingly described, broader humanistic burden experienced by patients is less well-characterized. This systematic literature review (SLR) aimed to synthesize evidence on health-related quality of life (HRQoL), symptoms, and patient-reported outcomes (PROs) in individuals with FSHD.
Methods: The SLR was conducted in accordance with PRISMA recommendations. MEDLINE, Embase, and Cochrane databases were searched from inception to August 2025, with additional hand-searches of key neuromuscular and disease-relevant conference proceedings. Studies evaluating humanistic burden in FSHD, including HRQoL, symptoms, and PROs, were eligible. Observational studies, clinical trials, and qualitative studies were included. Outcomes were synthesized descriptively by domain.
Results: 89 studies reported assessments of humanistic burden in FSHD using over 90 unique instruments. General HRQoL was the most frequently assessed (n=37), followed by fatigue (n=26), pain (n=20), disease-specific quality of life (n=18), and disability/function (n=9). Physical versus mental components of outcome instruments were consistently more impaired. Fatigue and pain were highly prevalent, with many patients reporting symptoms that interfered with daily activities and participation. Disease-specific measures highlighted substantial impacts related to muscle weakness, reduced independence, and activity limitations. Qualitative studies (n=16) further underscored psychosocial consequences, including challenges related to facial weakness, social interactions, uncertainty about disease progression, and concerns about future loss of independence.
Conclusions: FSHD is associated with a substantial and multidimensional humanistic burden affecting physical, functional, and psychosocial domains. The heterogeneity of PRO instruments used in FSHD highlights a lack of consensus on optimal measurements; an unmet need exists for a more standardized approach, and appreciation of clinical meaningfulness, to better capture patient experience and support patient-centered evaluation of emerging therapies.