A study by Hamel J. et al. assessed the most commonly reported complaints in a group of 328 FSHD patients (PRISM-FSHD). The most frequent were problems with the muscles of the shoulder girdle and arms (96.9%), reduced daily activity (94.7%), weakness of the abdominal muscles (93.8%), chronic fatigue (93.8%), and pain (87.7%). The patients also assessed that problems with the muscles of the shoulder girdle and arms and difficulties with movement had the most significant impact on reducing their quality of life. No differences were observed between the symptoms reported by women and men. Other studies reported that about one-fifth of FSHD1 patients become wheelchair dependent in the disease course. Among them, the most common were patients with 1-3 D4Z4 repeats. A more detailed description of clinical manifestations is provided below.
Muscle dystrophy
The muscle dystrophy development and progression tend to be slow. FSHD patients can even experience some breaks in disease progression. On the other hand, periods of sudden intensification may also occur. Some studies tried to measure (by manual muscle testing, quantitative myometry) an average loss of total strength per year and reported it as 5%. Near 12% of symptomatic FSHD1 patients will lose independent ambulation in 40 years from disease onset.
In typical cases, progressive muscle weakness initially affects the facial, scapular, and humeral muscles. Often, marked asymmetry of muscle involvement is seen. In later stages, muscle weakness involves the abdomen, lower limbs, and feet muscles. Frequently weakness of facial muscles goes unnoticed by the patient, and seeking medical help begins with the weakening of scapular muscles, causing problems with arms raising.
Symptoms of facial weakness tend to be more evident in the lower facial muscles. Patients may have difficulty drinking through the straw, whistling, and their relatives may notice that they sleep with their eyes not fully closed. Additionally, FSHD patients may have problems with pursing their lips or smiling. Scapular winging is frequently the initial finding. The shoulders usually slope forward with straight clavicles. Simultaneously there is marked pectoral muscles atrophy. The trapezius muscle is often affected, with apparent initial sparing of the deltoid muscle (a hallmark of FSHD). The right shoulder and arm muscles are usually more affected by atrophy than the left side. Abdominal muscle involvement often leads to severe hyperlordosis. Beevor's sign can be found in some patients during the neurological examination of lower abdominal muscles.
Contrary to other muscular dystrophies, contractures around weak muscles are not commonly observed. The lower limbs can be affected, usually starting with the tibialis anterior and gastrocnemius muscles. Some patients develop foot drop. Finally, with disease progression, weaknesses of proximal leg muscles can develop.
Beyond muscle dystrophy
Hearing loss
Hearing loss in FSHD patients mainly affects high-frequency sounds. Fortunately, patients rarely require hearing aids. In most cases, its course is subclinical, and currently, it is suggested that asymptomatic adults with FSHD do not need audiograms. However, some studies show a higher incidence of hearing loss in infantile-onset FSHD. For example, a cohort study by Lutz et al. found that 11/57 (19%) patients with infantile-onset FSHD had been diagnosed with hearing loss from birth to 7 years. Hearing impairment may, in some cases, be present and detected in newborns. Due to this fact, some studies indicate the need to include FSHD in the differential diagnosis of congenital hearing loss. Consensus-based recommendations suggest routine hearing screening from birth until school age in all FSHD patients.
Retinopathy
In most FSHD patients, the course of retinopathy is subclinical. However, frequently during fundus examination, tortuous retinal vessels are found (50–75%). This finding is less common in pediatric patients (about 37% of cases). Perhaps the reason is the later development of changes or less frequent fundus examination in asymptomatic children due to more difficult cooperation.
Nevertheless, in some cases, severe retinal vasculopathy develops - Coats disease. It can be a cause of vision loss and even blindness. Studies report that clinical manifestations of vision impairment are present in 0.8–1.7% of FSHD patients. What is more disturbing, the pediatric patients' cohorts show this occurrence at 6%. Being aware of this information has at least two consequences. First, FSHD should be included in the differential diagnosis in children with unexplained origin retinal vasculopathy and additional neuromuscular symptoms. Secondly, patients diagnosed with FSHD (primarily pediatric group) should undergo fundus examination because of the possibility of observing early changes and adequate intervention preventing them from further progression.
Pain
Many studies have suggested that pain is present in most FSHD patients. Moris et al. researched the U.K. FSHD Patient Registry and determined that 88.6% of 398 patients reported being currently in pain. 55.6% described the pain as chronic, and 30.4% said it was severe. The pain most frequently occurred in the shoulders (72.3%) and lower back (71.5%). Chronic pain was localized most commonly in the shoulder joint (45%). The study did not find any association between pain (both current and chronic) and D4Z4 repeats , age of disease onset, or motor function. There was, however, a correlation with gender - female patients experienced more pain.
Cardiac involvement
Cardiac involvement is not a common finding in FSHD. A study by Laforêt et al. of 100 FSHD patients showed that 5% have some cardiac involvement probably related to the disease. However, if we proceed to the detailed data, half of this group had only some mild changes. The other half presented with conduction defects and supraventricular arrhythmia. Based on this study, it can therefore be estimated that around 2.5% of FSHD patients may show clinically significant cardiac involvement. A more recent study by Ducharme-Smith et al. of 104 FSHD patients reported a higher incidence of mitral valve prolapse and RBBB when compared to the general population. In this cohort, 73 patients had ECGs performed, from which 7% had a complete RBBB, 5% had incomplete RBBB. These conduction abnormalities were mainly clinically irrelevant. In 53 patients, echocardiography was performed, and mitral valve prolapse was found in 9% without significant mitral regurgitation.
Epilepsy
Seizures are not common in FSHD patients and should be considered atypical presentation. In the majority, they tend to occur among early-onset FSHD patients and are associated with delays in psychomotor development and intellectual disability. Few reports described pediatric patients diagnosed initially with epileptic encephalopathy until muscle dystrophy became prominent.
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