From OMIMFacioscapulohumeral muscular dystrophy (FSHD) is a progressive skeletal muscle disorder with a highly variable phenotype. Most patients present as adults, although about 10% show symptoms before the age of 5 years, including from infancy in some cases. In general, the disease initially involves the upper body, including the face and the scapulae, followed by weakness at the foot dorsiflexors and hip girdles. Typical features are striking asymmetry of muscle involvement from side to side and sparing of bulbar extraocular and respiratory muscles. There is significant clinical variability, even within families, as well as incomplete penetrance. FSHD1 accounts for about 95% of patients. Facioscapulohumeral muscular dystrophy is the third most common hereditary disease of muscle after Duchenne (DMD; 310200) and myotonic (160900) dystrophy (Tawil et al., 1998; van den Boogaard et al., 2016; Johnson and Ankala, 2020; Schatzl et al., 2021).
Richards et al. (2012) and Schatzl et al. (2021) provided detailed reviews of FSHD, including clinical features, genetics, diagnosis, pathogenesis, and potential therapeutic avenues.
Genetic Heterogeneity of FSHD
Several other genetic forms of FSHD that are clinically indistinguishable from FSHD1, but not associated with physical contraction of the D4Z4 microsatellite repeat, have been identified. Historically, these forms have collectively been called 'FSHD2.' Tissue from patients with 'FSHD2' shows D4Z4 hypomethylation on chromosomes 4 and 10, suggesting the presence of unique transactivating factors, some of which have been identified. Genetic forms of FSHD other than FSHD1 account for about 5% of patients overall (summary by Hamanaka et al., 2020; Johnson and Ankala, 2020; review by Schatzl et al., 2021).
FSHD2 (158901) is caused by mutation in the SMCHD1 gene (614982) on chromosome 18p11; FSHD3 (619477) by mutation in the LRIF1 gene (615354) on chromosome 1p13; and FSHD4 (619478) by mutation in the DMNT3B gene (602900) on chromosome 20q11. Patients with FSHD2, FSHD3, and FSHD4 also carry a 'permissive haplotype' on chromosome 4 (4qA) that promotes DUX4 (606009) expression. There is significant clinical variability and incomplete penetrance.
http://www.omim.org/entry/158900 From MedlinePlus GeneticsFacioscapulohumeral muscular dystrophy is a disorder characterized by muscle weakness and wasting (atrophy). This condition gets its name from the muscles that are affected most often: those of the face (facio-), around the shoulder blades (scapulo-), and in the upper arms (humeral). The signs and symptoms of facioscapulohumeral muscular dystrophy usually appear in adolescence. However, the onset and severity of the condition varies widely. Milder cases may not become noticeable until later in life, whereas rare severe cases become apparent in infancy or early childhood.
Weakness involving the facial muscles or shoulders is usually the first symptom of this condition. Facial muscle weakness often makes it difficult to drink from a straw, whistle, or turn up the corners of the mouth when smiling. Weakness in muscles around the eyes can prevent the eyes from closing fully while a person is asleep, which can lead to dry eyes and other eye problems. For reasons that are unclear, weakness may be more severe in one side of the face than the other. Weak shoulder muscles tend to make the shoulder blades (scapulae) protrude from the back, a common sign known as scapular winging. Weakness in muscles of the shoulders and upper arms can make it difficult to raise the arms over the head or throw a ball.
The muscle weakness associated with facioscapulohumeral muscular dystrophy worsens slowly over decades and may spread to other parts of the body. Weakness in muscles of the lower legs can lead to a condition called foot drop, which affects walking and increases the risk of falls. Muscular weakness in the hips and pelvis can make it difficult to climb stairs or walk long distances. Additionally, affected individuals may have an exaggerated curvature of the lower back (lordosis) due to weak abdominal muscles. About 20 percent of affected individuals eventually require the use of a wheelchair.
Researchers have described two types of facioscapulohumeral muscular dystrophy: type 1 (FSHD1) and type 2 (FSHD2). The two types have the same signs and symptoms and are distinguished by their genetic cause.
Additional signs and symptoms of facioscapulohumeral muscular dystrophy can include mild high-tone hearing loss and abnormalities involving the light-sensitive tissue at the back of the eye (the retina). These signs are often not noticeable and may be discovered only during medical testing. Rarely, facioscapulohumeral muscular dystrophy affects the heart (cardiac) muscle or muscles needed for breathing.
https://medlineplus.gov/genetics/condition/facioscapulohumeral-muscular-dystrophy