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Back To Vidyya Facioscapulohumeral Disease


Major Effects Of Fshd Are Progressive Weakening And Loss Of Skeletal Muscle

Facioscapulohumeral muscular dystrophy (Landouzy-Déjérine disease) is an inheritable muscle disease, commonly called FSH or FSHD. Progressive weakening and loss of skeletal muscle are its major effects. It has significant medical and health impacts on individuals, families and society. Details about the nature of the disease and some basic knowledge of inheritance of genetic diseases are important to better understand FSHD.

What is FSHD?

FSHD is a common form of muscular dystrophy, defined by a specific set of symptoms that collectively characterize the disease. Its major symptom is the progressive weakening and loss of skeletal muscles. The usual location of these weaknesses at onset is the origin of the name: face (facio), shoulder girdle (scapulo) and upper arms (humeral). Early weaknesses of the muscles of the eye (open and close) and mouth (smile, pucker, whistle) are distinctive for FSHD. These symptoms, in combination with weaknesses in the muscles that stabilize the scapulae (shoulder blades), are often the basis of the physician’s diagnosis of FSHD. Other skeletal muscles invariably weaken. Involvement of muscles of the foot, hip girdle, and abdomen is common. Although the progression of FSHD is quite variable, it is usually slow. With FSHD, most affected people develop unbalanced (side to side) weaknesses. The reason for this asymmetry is unknown.

In more than half of FSHD cases, there are other symptoms like high-frequency hearing loss and/or abnormalities of blood vessels in the back of the eye. The vascular abnormalities in the back of the eye lead to visual problems in only about 1% of cases. Since these abnormalities are not exclusive of FSHD, one must be cautious of the fact that their presence alone, in an FSHD at-risk individual, is insufficient for a diagnosis of FSHD.

 

What causes FSHD?

By going from the large (muscle) to the small (DNA), one can partially understand the cause and origin of FSHD. DNA, short for deoxyribonucleic acid, is a long molecule found in the cells of our body. In association with some proteins, DNA makes up what we call our chromosomes. It holds the genetic instructions for our hereditary traits. Discrete segments of DNA, called genes, determine specific traits. Taken together, the combination of an estimated 100,000 genes makes each of us “an original.”

A sudden structural change in DNA, a mutation, causes FSHD. The FSHD gene(s) is unknown, but its approximate location is toward the end of the DNA of the long arm of chromosome 4. The genetic location of this DNA region is 4q35. Nearly all cases of FSHD are associated with a deletion of DNA in this region. Researchers are investigating the molecular connection of this deletion and FSHD. It is not yet certain whether the deleted DNA contains an active gene or changes the regulation or activity of a nearby FSHD gene (a position effect).

Perhaps 2% of FSHD cases are not linked to chromosome 4. Their linkage to any other chromosome or genetic feature is under investigation.

 

How does a person inherit FSHD?

Most individuals with FSHD inherited that mutation from a parent with the disease. Inheritance is the means of transmission of DNA, and therefore inheritable traits, from parent to child. Chromosomes are the vehicles for those transmissions. Each chromosome contains a long, threadlike strand of DNA. Human cells usually contain 46 chromosomes. Forty-four of the chromosomes, also called autosomes, are homologous pairs and numbered from 1 though 22. The remaining chromosome pair consists of the nonhomologous chromosomes X and Y, the sex chromosomes. From each parent, children inherit one member of each pair of 46 chromosomes. A mother donates an X chromosome, and a father donates either an X or Y chromosome.

FSHD is the result of a DNA mutation on one member of the chromosome 4 pair. FSHD is highly penetrant. When a person inherits a chromosome 4 with the FSHD mutation, there is high probability that discernible muscle weaknesses will develop. Since weakness still occurs in the presence of the normal member of the chromosome 4 pair, the disease is considered dominant. FSHD is therefore an autosomal dominant inherited disease. Since each parent donates only one member of each chromosome pair to a child, the probability of passing the disease to an offspring is 50%. (See Figure.)

 

What are sporadic cases of FSHD?

Sporadic FSHD cases are those resulting from a new mutation. Studies report 10% to as high as 33% of FSHD cases as sporadic. Approximately 20% of reported sporadic cases are those inherited from a seemingly unaffected parent who is a germline mosaic. Although the parent appears unaffected, the children are at risk. In the remaining sporadic cases, a new spontaneous mutation results in a chromosome 4 deletion that causes FSHD. When the 4q35 deletion fragment appears in a sporadic FSHD case, it is transmitted in an autosomal dominant manner to succeeding generations. The probability of passing the disease to an offspring is 50%.

 

How many people have FSHD?

It is difficult to calculate the exact incidence of FSHD. It may be under reported, but an accepted estimate of its occurrence in the general population is one in 20,000. FSHD occurs in all racial groups. It occurs with equal frequency in both sexes.

 

When do symptoms appear?

Although the FSHD gene is present at birth, weaknesses are generally noticeable during the second decade. A physician can usually recognize and diagnose FSHD beyond the age of 20. However, it is important to realize that the onset of FSHD is variable. Sometimes, muscle weaknesses are slight throughout adulthood. In perhaps 5% of cases of FSHD, a young child or an infant develops symptoms. In infantile FSHD (IFSHD) there are early facial weaknesses during the first two years of life, typical muscle weaknesses of FSHD, and in some of these children, early hearing losses and retinal abnormalities.

Early onset and infantile cases of FSHD often pose special problems arising from severity of the symptoms and schooling issues. T

 

What is the prognosis of FSHD?

Predicting the course and outcome of the disease, i.e., the prognosis, has its clinical certainties and uncertainties. There is certainty that some skeletal muscles will weaken and waste throughout life, and that this can and often does cause limitations on personal and occupational activities. FSHD appears not to diminish the intellect. The heart and internal (smooth) muscles seem spared and, with rare exceptions, those with FSHD have a normal life span.

There are uncertainties. The rapidity and extent of muscle loss differ considerably among FSHD patients, even among members of the same family. Some report few difficulties throughout life, while others may need a wheelchair as walking becomes too difficult or impossible. The degree of severity in an FSHD parent cannot accurately predict the extent of disability that may develop in that parent’s child.

As a group, people with FSHD are well adjusted, educated and motivated. They cope with a legion of adaptations. Muscle and motion are an important part of the full expression of much of life. Often, there are losses difficult to define in clinical terms. Interactions with family, friends and associates may become limited. The accompanying losses often eclipse the clinical certainties and are an unspoken and significant part of the FSHD prognosis.

 

If a family member has FSHD, could I have the FSHD mutation?

Yes. If one has a blood parent, sibling or other relative who has the FSHD mutation, there may be a risk of carrying that mutation. Professionals with knowledge of genetics and inheritance of FSHD can advise regarding that risk in individual circumstances. The FSH Society can provide answers and referrals about questions of risk.

 

Can a physician diagnose FSHD?

Yes. Even an adult at risk, with no obvious symptoms, should avail themselves of a clinical diagnosis if they wish reassurance. Examinations by clinicians familiar with the disease are quite dependable when there are symptoms that follow an expected location and pattern of weakening muscles. By the age of 20, muscle weakness can be found approximately 95% of the time in affected individuals. Often the physician will supplement a physical examination with inquires about a possible family history of FSHD, measurement of specific enzyme levels in the blood, an electromyograph (EMG) and/or a muscle biopsy. An EMG records abnormal electrical activity of a functioning skeletal muscle. A biopsy consists of a small piece of muscle tissue, analyzed for visible abnormalities. A thorough examination will detect the disease in approximately 95% of affected individuals beyond the age of 20. However, the diagnosis may still be equivocal at younger ages and with some at-risk adults with mild or asymptomatic cases. This uncertainty can occur during years where there are important vocational, marital and family planning choices at issue. This has created a real need in the FSHD population for a DNA test for the disease.

 

Is a DNA test for FSHD possible?

Yes. There is now a DNA test for FSHD in the clinical arsenal. It is highly reliable for many cases where diagnosis of FSHD is uncertain or impossible. The test detects the 4q35 DNA deletion described above. Although several factors may occasionally complicate the test, confirmation of the 4q35 deletion is 98% reliable as a presumptive diagnosis of FSHD. The test requires no more than a small amount of blood that one’s physician sends to a testing laboratory. The laboratory extracts sufficient DNA for the test from the cells present in the blood. An individual should consult their own physician and the laboratories about the DNA diagnostic test.

Currently, there is no DNA test available for those few cases where there is no linkage between FSHD and chromosome 4.

 

Is there a prenatal test for FSHD?

Yes. Using the same technology of the DNA test described above, prenatal testing is possible. An individual who is interested in a prenatal test for FSHD should consult with their physician.

 

Are treatments and aids available for FSHD?

There is no treatment or cure for FSHD. There are, however, things that can alleviate its effects. Since muscles do their work through stimulation by nerves, neurologists are concerned with muscle and are often the primary physicians of muscle disease clinics. Physiatrists are physicians who work with chronic neuromuscular conditions. Periodic visits with a neurologist or physiatrist are useful to monitor the progress of FSHD and to obtain referrals to other professionals and services. An orthopedist, one concerned with the skeletal system and associated muscles, joints and ligaments, can advise about mobility issues and other functional problems of the muscular/skeletal system.

Physical therapy, including light exercise, helps preserve flexibility. Swimming is especially helpful in this regard by making many movements easier. One should stay as active as possible, with rest breaks as needed during exercise and activities. Occupational therapy can help with suggestions for adaptations and physical aids that can often partially free an FSHD patient from some constrictions of the disease. Dietitians can help maintain a good diet and avoid unnecessary weight to reduce stress on already weakened muscles. In addition, speech and hearing therapists can help with limitations imposed by hearing loss and weakened facial musculature to improve speech and communication.

Sometimes a surgeon attaches the scapulae (shoulder blades) to the back to improve motion of the arms. An individual who is considering such surgery should consult with their neurologist or physiatrist and an orthopedic surgeon. Discussion of this procedure with individuals who have undergone the surgery is important. The FSH Society provides referrals to physicians and other professionals.

Pain is part of FSHD in many patients. No specific treatments are available. Pain medication and mild physiotherapy are often prescribed with moderate results.

 


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Editor: Susan K. Boyer, RN
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