Abstract The defining clinical features include the onset of weakness of the facial or shoulder girdle muscles, leading eventually to the wasting of these muscles (Fig. 8.1). Significant facial weakness is evident in more than half of all affected FSHD patients. As the disease progresses, the muscles of the shoulder girdle, the scapula fixators, and the upper arm muscles (especially the biceps and triceps) may become affected. Weakness and atrophy may eventually involve many other skeletal muscles, including the musculature of the pelvic girdle and the foot extensor muscles may become involved, resulting in footdrop. Some patients may display involvement of the proximal muscles of the lower limb prior to any evidence of weakness of the distal muscles. Involvement of the musculature of the pelvic girdle is observed infrequently. However, patients who exhibit pelvic girdle muscle weakness before the age of 20 years are more likely to become wheelchair-bound, and at an earlier age. Studies have indicated that although 10–20 per cent of all FSHD gene carriers will require a wheelchair by their fourth decade, a further 22–30 per cent of carriers will only be mildly affected, or may even remain virtually asymptomatic throughout their lives.