Integration of UK and USA FSHD1 registries identifies 7 clinical presentations and associates smoking status with earlier symptom onset



Poster Number: 106


Christopher Banerji PhD, MBBS, Jeffery Statland MD, Peter Zammit PhD


1. King's College London, 2. University of Kansas Medical Center, 3. King's College London

Facioscapulohumeral muscular dystrophy 1 (FSHD1) is a prevalent inherited skeletal myopathy linked to truncation of the D4Z4 macrosatellite at chromosome 4q35. Though classically presenting first in the facial musculature before progressing to the shoulder girdle and latterly the lower limbs, FSHD1 is characterised by considerable clinical heterogeneity. We previously identified 4 distinct clinical presentations in the UK FSHD registry, via analysis of 643 patients. Here we investigate 512 patients described by the USA FSHD registry, with an average annual follow up of 8 years, reporting a wide array of variables. By categorising self-reported symptoms as corresponding to facial, upper or lower limb weaknesses we performed multivariate time to event analysis on an amalgam of 10 common FSHD symptoms. We found that short D4Z4 repeat length associated with earlier onset of all muscle weakness symptoms, in line with previous studies. Importantly, patients who reported smoking cigarettes experienced an earlier onset of both facial and lower body muscle weakness symptoms, suggesting a role for smoking cessation in FSHD1 patients. Self-reported hypertension associated with a slower onset of facial weakness. Analysis of medication use revealed that patients who experienced earlier onset disease were more likely to take analgesia, while patients with later symptoms were more likely to take certain anti-hypertensives. Clustering analysis on time to symptom development on 171 USA FSHD1 patients who experienced all three of the most common symptoms assigned to each muscle group, revealed 4 distinct clinical presentations, including facial sparing and early upper limb weakness subtypes. Lastly, clustering on integrated data describing 213 UK and 171 USA FSHD1 patients and adjusting for registry membership revealed 7 distinct clinical presentations of FSHD1.