About facioscapulohumeral muscular dystrophy

What is facioscapulohumeral muscular dystrophy?

Facioscapulohumeral muscular dystrophy (FSHD), also known as Landouzy-Dejerine muscular dystrophy, is a neuromuscular disorder. Symptom onset usually occurs in adolescence or early adulthood; however, less commonly, symptoms may become apparent as early as infancy or early childhood.

The disorder is typically initially characterized by weakness of facial, shoulder, and/or upper arm muscles. Associated abnormalities may include an impaired ability to completely close the eyes, limited movements of the lips, and difficulties raising the arms over the head. Affected individuals may also eventually develop weakness and associated wasting (atrophy) of muscles of the hips and thighs and/or involvement of lower leg muscles.

Although the disease course may be variable, FSHD is most typically characterized by relatively slow disease progression. Specific symptoms and findings may also vary in range and severity, including among affected members of the same family (kindred).

FSHD is usually inherited as an autosomal dominant trait. However, in up to approximately 30 percent of affected individuals, there is no apparent family history of the disorder. In some of these cases, FSHD may be due to new genetic changes (mutations) that appear to occur spontaneously for unknown reasons (sporadically).

What are the symptoms for facioscapulohumeral muscular dystrophy?

FSHD may initially involve Weakness of muscles of the face, shoulder girdle and arms. Facial Weakness may result in limited movements of the lips, causing difficulties whistling, using a straw, or puckering the lips. Affected individuals may also develop a distinctive “mask-like” facial appearance. Upper facial Weakness may also lead to an inability to completely close the eyes during sleep.

FSHD is also typically associated with weakening and atrophy of muscles of the neck and shoulder blades and muscles at the front and back of the upper arms (biceps and triceps brachii muscles). With disease progression, there is a decrease in the ability to lift the arms due to Weakness of muscles stabilizing the shoulder blades; and “scapular winging,” one of the most common initial finding, characterized by abnormal prominence of the borders of the shoulder blades. This finding tends to become more obvious when affected individuals attempt to raise their arms to the side (laterally). In addition, when viewed from the front, the collarbones (clavicles) may appear to sag. Some affected individuals may also develop wrist drop or downward flexion of the wrist due to Weakness of certain muscles of the fingers and hands.

FSHD may also be characterized by Weakness and atrophy of other muscles, including abdominal wall, hip, and thigh muscles. Involvement of the muscle that rotates and moves the thigh outward (gluteus medius) may cause affected individuals to sway or lurch toward the affected side while walking (Trendelenburg gait). There may also be Weakness of muscles of the lower legs and feet. Such involvement may lead to a condition known as footdrop, which is characterized by an impaired ability to flex or bend the foot upward. In some affected individuals, involvement of certain muscles may result in unusually pronounced inward curvature of the lower region of the spine (lordosis) or abnormal front-to-back and sideways spinal curvature (kyphoscoliosis).

For unknown reasons, in most individuals with FSHD, the degree of Muscle Weakness may differ from one side of the body to the other (asymmetrical).

Those with the disorder may have relatively slow or moderate progression of Muscle Weakness or, in some cases, apparently non-progressive involvement of certain muscles. However, evidence suggests that the disease course is most frequently characterized by slow progression with short periods of rapid muscle deterioration. Associated Muscle Weakness may result in minimal disability or, in other people, lead to difficulties speaking; abnormalities in the manner of walking (gait disturbances); and/or an impaired ability to perform certain activities of daily living. In approximately 20% of those affected, disease progression may lead to severe Muscle Weakness that necessitates the use of a wheelchair or other mobility equipment. Families have been described in which disease manifestations ranged from minor facial Weakness in a parent to severe infantile onset in an affected child.

In some individuals with FSHD, particularly those with early onset, the disorder may also be associated with hearing impairment and/or abnormalities of blood vessels within the nerve-rich, innermost membrane of the eye (retinal vasculopathy) that may, in rare cases, lead to visual impairment.

Two types of FSHD have been described, FSHD1 (95% of those affected) and FSHD2 (5% of those affected). FSHD1 and FSHD2 have the same signs and symptoms but different genetic causes.

What are the causes for facioscapulohumeral muscular dystrophy?

FSHD1 is caused by abnormal expression of the DUX4 gene, which is located in the D4Z4 region of chromosome 4. Normally, the DNA in the D4Z4 region is hypermethylated (has many methyl groups: 1 carbon atom and 3 hydrogen atoms) and includes 11-100 repeated segments of DNA. In individuals with FSHD1, this region of chromosome 4 is shortened and contains 1-10 repeats and fewer methyl groups. The lack of methyl groups allows the DUX4 gene to be “turned on” and produce DUX4 protein in cells and tissues where it is usually not produced, resulting in progressive muscle weakness and atrophy. Generally, a smaller number of repeats is associated with more severe disease.

FSHD1 is an autosomal dominant genetic condition. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary to cause a particular disease. The abnormal gene can be inherited from either parent or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy. The risk is the same for males and females.

In approximately 30 percent of individuals with FSHD1, there is no apparent family history of the disorder and in these people FSHD is thought to be caused by new mutations.

FSHD2 is also an autosomal dominant genetic condition. People with FSHD2 have a mutation in the SMCHD1 gene that results in demethylation of the D4Z4 region, allowing misexpression of the DUX4 gene and resulting in progressive muscle weakness and atrophy.

What are the treatments for facioscapulohumeral muscular dystrophy?

The treatment of FSHD is directed toward the specific symptoms that are apparent in each individual. Such treatment may require the coordinated efforts of a team of medical professionals, such as physicians who specialize in the treatment of neurological disorders (neurologists); physicians who diagnose and treat disorders of the skeleton, joints, muscles, and related tissues (orthopedists); physicians who specialize in physical medicine and rehabilitation (physiatrists); specialists who assess and treat hearing problems (audiologists); physicians who specialize in respiration (pulmonologists) and/or other health care professionals.

Disease management may include orthopedic measures and physical therapy to help maintain muscle flexibility, counter atrophy and manage pain. Several studies indicate that those with FSHD benefit from exercise. Various physical and adaptive aids may be helpful in performing certain activities. Ankle-foot orthotics can help with walking. In some cases, severe muscle weakness may necessitate the use of wheelchairs, motorized carts, and other mobility and physical aids.

In addition, speech therapy, use of appropriate assistive devices, and/or other supportive techniques may help to improve speech and communication problems associated with hearing impairment and/or facial weakness.

In some people, recommended treatment may include surgery to mechanically attach the shoulder blades to the chest wall in order to help stabilize the scapulae and improve mobility of the upper arms.

Pulmonary function testing is recommended for all with FSHD. Depending in these results, a sleep study may be recommended to determine breathing capacity while supine and asleep. Noninvasive ventilator support, usually beginning at night, is provided for those whose pulmonary function testing and sleep study are suggestive of respiratory compromise.

Testing for retinal eye problems may be indicated for those with severe disease. Hearing testing may be indicated for children and some adults. Genetic counseling is recommended for affected individuals and their families. Other treatment for this disorder is symptomatic and supportive.

What are the risk factors for facioscapulohumeral muscular dystrophy?

Facioscapulohumeral muscular dystrophy (FSHD) is a genetic illness acquired in an autosomal dominant manner. FSHD affects skeletal muscle groups, including those of the face, shoulder girdle and lower extremities. The development of the symptoms occurs over a long period, typically in the second decade of life. The severity of the disease varies widely across the affected individuals. Men are more severely affected than women when diagnosed at later stages in life.

Risk factors for FSHD:
1. The pathology of the disease is due to an interaction of genetics of the gene DUX4 and the array of D4Z4 macro satellites on chromosomes 4 and 10. Based on the underlying type of genetic interaction, FSHD is of type 1 and type 2.
2. The only risk factor for the disease is a familial history of the defected genes.
70-90 % of the affected individuals have a parent with clinical findings and at least one pathogenic allele of the D4Z4 gene. On the other hand, 10-30 % of probands with the disease have de novo mutation.
3. Proband serves as the starting point of a genetic study of a family, and de novo mutation refers to the one that has occurred in germ cells in the parents of the person in whom the disease appears for the first time in the family.
4. Genetic counseling is the only way to reduce the risk of inheriting the disease.

Weakness of facial muscles, muscles in the neck, shoulder blades, and muscles of upper arms,Scapular winging, limited lip movements, difficulty in raising arms,Weakness of the muscles in abdominal walls, hip, and thighs,Weakness of lower legs and feet,In rare cases, loss of hearing, and retinal vasculopathy
A genetic muscle disorder in which the muscles of the face, shoulder blades, and upper arms are among the most affected
Occupational therapy to help improve activities of daily living,Oral albuterol to increase muscle mass,Speech therapy,Surgery to fix a winged scapula,Walking aids and foot support devices if there is ankle weakness

Video related to facioscapulohumeral muscular dystrophy