Muscular Dystrophies:

FACIO SCAPULO HUMERAL

What Are Muscular Dystrophies?

The muscular dystrophies are a group of muscle diseases which have three features in common: they are hereditary; they are progressive; and each causes a characteristic, selective pattern of weakness.

Please contact the Muscular Dystrophy Association for information about other types of muscular dystrophy and related neuromuscular disorders.

What is Facioscapulohumeral Dystrophy?

Facioscapulohumeral dystrophy (FSH) is a genetic condition, affecting approximately 1 in 20,000 Caucasians. It is the third most common neuromuscular condition after Duchenne Muscular Dystrophy and Myotonic Dystrophy, although its frequency may vary in different places and quite possibly in different racial groups. FSH has been previously known as Landouzy-Dejerine and facioscapuloperoneal muscular dystrophy.

The term Facioscapulohumeral uses three Latin words to describe the characteristic features. Facio means face, scapula means shoulder blade and humerus is Latin for the upper arm. Muscular dystrophy refers to muscle weakness and wasting. Thus, in Facioscapulohumeral dystrophy the muscles typically affected are those of the face, shoulder blade and upper arms. FSH may also spread to other parts of the body in the course of the disease and often only one side of the body is affected. FSH does not typically affect other body systems so sensation, bowel, bladder and sexual function all remain normal. Intellectual abilities are also usually not affected.

Symptoms may appear at any time from childhood till a person is in their 50’s. Symptoms in men are generally more severe and occur at a younger age than in women. In fact, some women do not realise they have the condition until they are genetically tested.

What causes Facioscapulohumeral Dystrophy?

It is a genetic condition, present from when or soon after egg and sperm come together at conception. As it is a genetic condition, FSH is caused by a change or mutation in a gene. The human genome consists of 23 pairs of chromosomes, which contain genes composed of DNA (deoxyribonucleic acid). The chromosome carrying the defect causing FSH was identified in 1990 as being chromosome 4. Normally mutations occur in the gene, which contain the recipes for proteins, so the result is that the protein normally produced is absent or abnormal. Scientists were surprised to discover that the mutation causing FSH is not in a gene. Instead, the mutation leads to a deletion in a part of DNA called a repeat sequence. Normally, at a particular site on the gene map, each of us has many copies of a particular sequence of DNA, arranged like a train of identical carriages. FSH is caused when the number of copies is reduced below a certain level, like a train having too few carriages. It is thought that the repeat sequence may inhibit the activity of neighbouring genes. This phenomen is called transcriptional derepression.

Normally, chromosome 4 contains between 10-100’s of copies of this repeat sequence, which is called D4ZA. In FSH, there are less than 10 repeated copies of this gene. The deletion allows the neighbouring genes to produce too much of a certain protein and ultimately this overproduction results in cell death. The size of the deletion is related to the severity of FSH, with large deletions causing congenital onset (babies born with FSH) and severe symptoms. Small deletions on the other hand, result in late onset, between 15-23 years and mild symptoms. The congenital onset form is rare, comprising 2% of all FSH cases. It is likely the overactive genes produce a muscle specific protein, explaining why it is the muscle cells that are primarily affected. This mechanism requires further investigation, as the unusual pattern of muscles affected and why only one side of the body may be affected remains to be explained.

Also requiring further clarification is if the activity of one or several genes is altered by this deletion. It is possible that one gene has different effects in different cells, so it is able to cause problems in skeletal muscle as well as eye and hearing problems. Another explanation is that three or more separate genes are all affected by the deletion. Again, this remains to be defined.

Symptoms

Symptoms of FSH can be classified into two groups – adult-onset, which is usually mild and congenital-onset, which is typically more severe.

Although the classical symptoms of FSH involve the muscles of the face, shoulder blade and upper arms, there is variability in which areas are affected. Some people may experience no symptoms in the face muscles, with the lower limb muscles affected instead. This form is known as “Atypical FSH” as the same part of chromosome 4 is affected as in classical FSH.

Symptoms include:

Facial muscle weakness is usually the first symptom and is noticeable by difficulties in puckering the mouth, as in whistling, or difficulties with the eye muscles causing for example, problems in closing the eyes properly at night. Facial muscle weakness may also cause difficulty in pronouncing certain words; the person may have pouting mouth or an unusual smile.

Another common early sign may be noticed in the shoulder blades (scapula) with weakness preventing movements such as the throwing of balls. Muscle weakness around the scapula allows it to wing out.

The muscles of the lower leg may weaken. This may cause difficulties in picking the front part of the foot up during walking – “foot drop.” Lower leg weakness may also make walking up hills or on uneven surfaces difficult.

An excessive curve in the lower back may develop, due to abdominal muscle weakness. This weakness is called a lordosis and may develop early on in the disorder.

Sometimes the muscles surrounding the hip and those of the upper legs also become weak. This can cause problems running, rising from a chair or negotiating stairs.

Contractures may develop as scar tissue replaces normal elastic tissue. This prevents normal movement in that joint and makes the tissues resistant to stretching. Contractures tend occur in the ankles and may require surgery to release them.

Damage to the retina of the eye is infrequently associated with symptoms of FSH, but any unexplained visual problems should be reported. More severe forms of FSH are associated with Coat’s disease, a disease of the retina. Some doctors recommend that infants with the genetic risk of FSH should undergo occasional eye tests.

Hearing loss may occur in severe FSH and most FSH individuals experience some degree of hearing difficulty. Complete hearing loss is associated with severe childhood cases.

Intellectual and cognitive (understanding) difficulties are very uncommon in adults with FSH and there are many FSH people including those in whom symptoms began in childhood, in intellectually demanding occupations. Rarely, learning difficulties may occur. It is important that real cases are not confused with apparent non-responsiveness. Very bright children may appear unresponsive due to a combination of deafness and facial immobility, so it is important they are accurately diagnosed.

Epilepsy may develop in the more severe forms of FSH.

Unlike many of the other muscular dystrophies, cardiac and respiratory problems are rare in FSH. However, monitoring of cardiac and respiratory function may be recommended for some patients.

Inflammation of the muscles can occur in FSH. It is not clear whether inflammation is a cause or a result of the disease. Inflammation can be a source of pain in FSH, as can the altered joint position resulting from muscle weakness.

Severity and progression

The severity of FSH is widely variable. It tends to progress slowly, and there may be long periods where relatively little change in symptoms occur. It may take 30 years for serious problems to develop, if at all. Approximately 20% of FSH patients require a wheelchair and this may only be occasionally. Life expectancy is that of the normal population.

Men tend to show more weakness and from a slightly earlier age than women. The reason for this is not yet clear. Within large families, and therefore excluding the most severe cases, women are more likely to be less severely affected and so could be unaware that they have inherited the condition

Is Facioscapulohumeral Dystrophy inherited?

FSH is a genetic disorder and the mutation may either be inherited from the parents or arise spontaneously. Between 70-90% of the mutations are inherited from the parents in an autosomal dominant manner, with between 10-30% of defects arising spontaneously. These sporadic mutations occur randomly during a child’s conception.

22 pairs of human chromosomes are autosomes, meaning they are not involved in sex determination. The 23rd pair of chromosomes are the sex chromosomes, with males having 1 X and 1 Y chromosome, and females having two X-chromosomes. An autosomal dominant disorder means that only one copy of the defect is required for the disease to develop. This is in contrast to autosomal reccessive disorders where two copies of the defect are required for the disease to develop. As FSH is an autosomal dominant disorder, there is a 50% chance of the child of an affected parent to inherit the faulty gene and therefore develop the condition.

It is possible for a parent to have the gene change, yet be unaware of it. One third of people with the mutation experience no symptoms. This is more common in women with the majority of males (95%) with the gene change experiencing symptoms by the age of 30. Therefore sons are more likely to be affected than daughters.

Genetic testing gives the family information on whether the altered gene is in the family or whether the disorder is the result of a spontaneous mutation. Prenatal testing for the defect is also possible. Genetic counselling provides information and support to an individual or to a family about genetic disorders. Genetic services are available in Victoria and across most states of Australia. You may contact these services directly, or be referred by your doctor or other health professional.

Diagnosis

Genetic diagnosis can almost always determine the presence of the genetic defect causing FSH. In families where the disease is known to exist, the signs of the disease and a DNA test are sometimes all that is needed to confirm the diagnosis. Often, however, this is not the first test conductions, instead is generally the last step in the diagnosis process. This is because the amount of information in a person’s DNA is so large, the lab needs to have a clue as to where to look.

Therefore other tests that may be done to confirm the diagnosis may include:

A blood test can assess the presence of an enzyme, Creatine Kinase (or CK). This enzyme is usually restricted to muscle cells. When muscle cells are damaged, the creatine kinase leaks out and into the blood. This results in higher than normal levels of creatine kinase in the blood. However, as elevated creatine kinase is also a feature of other forms of muscular dystrophies, this test is not conclusive.

The electromyogram (EMG) is a test that measures the electrical activity of muscles. The EMG may show both nerve and muscle involvement, which is typical of FSH.

A muscle biopsy involves removing a small amount of muscle tissue. This can give a lot of information on the condition of the muscle and can help to either rule out other diagnoses or to confirm the FSH diagnosis.

Other tests include nerve conduction velocity (the speed with which the nerve is able to transmit impulses), hearing tests and tests of cardiac function (electrocardiogram).

Treatment

FSH is currently untreatable, largely because little is known about the mechanisms causing muscle damage in this disease. However, there are many things that can be done to alleviate the symptoms.

What management is recommended?

Exercise is generally considered to be beneficial in FSH, maintaining both muscle strength and flexibility. Swimming is a good way to exercise muscles without straining them and many find the support of water helpful. Moderation is the key with any exercise you decide to undertake and it is important to realise that people with FSH may tire more quickly than others. Remember to take rest breaks as you need to. Intense exercise is not recommended - it may cause muscle cramping, extreme fatigue and may further contribute to muscle damage.

Regular stretching is important to maintain muscle length and to prevent unnecessary tightness. Physiotherapists are specialists in treating neuromuscular conditions and are able to give expert advice. Physiotherapy can benefit an individual affected with FSH by assisting them maintaining their optimum health, prevent and delay secondary complications, maximise functional ability as well as improving and maintaining quality of life. Each person gets a tailored, individual plan that incorporates a number of recommendations that are specific to them.

A good balanced diet incorporating plenty of fresh fruit and vegetables is advised. No vitamin or dietary supplements are necessary unless a specific deficiency has been identified.

Weight control is important, as excess weight will contribute to tiredness and weakness. Hence calorie intake needs to reflect energy needs, and this is best done at an early stage. Keeping the correct weight will help the individual to move more easily and will assist carers who may have to lift them. It will also place less strain on the already weakened muscles.

Assistive devices, special equipment and aides, home and vehicle alterations are further ways that can make life with FSH easier. These are available through an Occupational Therapist.

Foot-drop due to muscle weakness in the lower legs makes walking difficult. The use of an ankle-foot orthosis (AFO) can help to maintain the foot in the correct position when walking. Some people develop exaggerated curves in the lumbar spine (lower back). These can be corrected with the use of braces and supports to assist maintaining a more correct spinal posture.

Many people with FSH may experience pain. There are no specific treatments for this, although physiotherapy and medication may help manage it.

Medical Treatment:

The winged scapula makes normal arm movements difficult, so surgically fixing the scapula to the ribs is able to decrease winging and improve arm mobility. An Orthopaedic Surgeon would recommend whether this surgery would be of assistance.

Surgery on the eyelids may be beneficial where there is incomplete closure of the lids. Incomplete eyelid closure can cause problems with the eye such as inflammation of the cornea (keratitis), so it is important not to ignore the early signs of waking up with dry and red eyes.

What research is being done?

Scientists are currently looking for the actual genes and gene products that are disrupted in FSH. Understanding the cause of symptoms in FSH will greatly assist in knowing how to best treat the condition. One area that is being investigated is the mechanism by which the repeat sequence, D4ZA is able to repress the neighbouring genes. Finding a way to block these over-active genes could lead to effective treatment by developing agents to mimic the normal inhibitory process.

On muscle biopsy it is common to observe marked inflammation in the muscle fibres. This inflammation is greater than what would be predicted by the damage occurring in the muscle. It is unclear whether this inflammation is actually a cause of FSH or a result. Scientists are currently attempting to clarify this and this may provide potential treatment options with the use of specific anti-inflammatory agents.

Further Pregnancies:

Accurate pre-natal testing, performed by either chorionic villous biopsy (CVS) (performed usually at 11 weeks gestation) or by amniocentesis (performed around 15 weeks gestation), is now available to most couples who would wish this, and whose offspring would be at risk of FSHD. It is essential that genetic (DNA) tests be performed first on blood samples from the affected parent or child to define the DNA mutation in that family. Blood samples would usually be required from both parents, and in some cases from other affected relatives. Both procedures are now widely available, although the tissue sample obtained would be forwarded to one of a few specialist genetic laboratories. Couples considering this should consult with their local genetic service that would advise accordingly, preferably prior to becoming pregnant.

Additional Information

OMIM Link 1
FSH Society An organisation dedicated to patients and researchers and for those seeking information on FSH.
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