Frequent co-occurrence of AChR-positive myasthenia gravis in facioscapulohumeral muscular dystrophy suggests a novel disease association

Background: Facioscapulohumeral muscular dystrophy (FSHD) is a genetic myopathy caused by inappropriate expression of the DUX4 gene. Myasthenia gravis (MG) is an autoimmune disorder targeting the neuromuscular junction, usually via anti-acetylcholine receptor (AChR) antibodies. Both conditions are rare, though isolated reports describe their co-occurrence. We aimed to determine whether the frequency of co-existing FSHD and MG exceeds chance expectation.

Methods: We conducted a retrospective observational study across UK MG clinics. Genetically confirmed FSHD cases with AChR antibody-positive MG were identified through clinician report and historical review. Clinical data were extracted where available, including age of onset, antibody titres, thymic findings, and D4Z4 repeat size.

Results: 13 cases of dual FSHD and MG were identified, of which 9 were living. Based on prevalence estimates (FSHD 12/100,000, MG 20/100,000), only 1.6 cases would be expected in the UK by chance; our findings represent a 5-fold increase (95% CI: 2.6–10.7; p = 0.000045). Detailed data were available for 10 patients: 7 were male, median age of MG onset was 55.5 years (range 30–75). MG onset followed FSHD in 8/10 (mean interval 14.9 years). All tested patients had genetically confirmed FSHD1 and positive AChR antibodies. Thymic pathology was identified in only one patient.

Conclusion: The observed frequency of MG in FSHD patients exceeds chance expectation, suggesting a novel disease association. DUX4 is aberrantly expressed in thymus and muscle in FSHD, and may predispose to MG. Clinicians should consider MG in atypical FSHD presentations. Further studies are warranted to explore this association.