Genetic diseases are inherited disorders reflecting gene mutations or abnormalities In chromosome structure or number and resulting in functional or anatomical changes. The frequency of chromosome abnormalities in the United States is 1 in about 200 live births. Approximately 5060 percent of all recognized spontaneous abortions are chromosomally abnormal. Six in every 100 stillbirths have chromosome abnormalities. and 6 in every 100 neonatal deaths are associated with chromosome defects. Gene transmission, or heredity, in families is most often identified by the function of an altered gene. Genetic diseases can be inherited in a manner similar to that of normal traits.
These diseases include single-gene disorders that are autosomal dominant, sex-linked dominant, autosomal recessive, or sex-linked recessive. They also include multifactorial disorders, resulting from more than one gene often interacting With environmental factors.
In most cases of sex-linked recessive traits, the mother is heterozygous but unaffected” she is a carrier. She has a 50 percent chance of producing affected sons through transmission of page 2 an X chromosome carrying the gene mutation.
Her daughters have a 50 percent chance of being heterozygous like the mother. If an affected male is able to reproduce and marries a homozygous normal female, none of his children will be affected, but all of his daughters Will be heterozygous for the sex-linked gene. His sons do not inherit the disease. Muscular dystrophy (MD) refers to a group of genetic diseases, some of which are sexrlinked. which are characterized by progressive weakness and degeneration of the skeletal or voluntaiy muscles which control movement. The word dystrophy comes from Latin and Greek roots meaning “faulty nutrition”.
When doctors first began describing muscle diseases in the 19th century, they had few tools other than their own eyes. Muscles in many diseases appeared to be wasting away, and the doctors theorized that they somehow weren‘t being properly nourished. Today, we know that many muscle-wasting diseases are caused by defects in genes for muscle proteins. Most of these proteins appear to play a role in supporting the structure of muscle fibers, although some may play a role in the biochemical processes that go on in muscle fibers. The muscles of the heart and some other involuntary muscles are also affected in some forms of MD. and a few forms involve other organs as well. page 3 The major forms of MD include myotonic, Duchenne,Becker, limb-girdle, facioscapulohumeral, congenital, oculopharyngeal, distal, and Emery-Dreifuss. Duchenne is the most common form of MD affecting children, and myotonic MD is the most common form affecting adults. MD can affect people of all ages. Although some forms first become apparent in infancy or childhood, others may not appear until middle age or later.
These forms differ in severity, age of onset, muscles first and most often affected. the rate at which symptoms progress, and the way the disorders are inherited. Some of these names are based on the locations of affected muscles. For example. “facioscapuiohumeral” refers to the muscles that move the face, scapula (shoulder blade) and humerus (upper arm bone). Others are based on the type of muscle problem involved (“myotonic” means difficulty relaxing muscles), the age of onset of the disease (as in “congenital,“ or birth-onset, dystrophy), or the doctors who first described the disease (Duchenne, Becker, Emery and Dreifuss are doctors‘ names. As the genetic causes of the muscular dystrophies are discovered, doctors are beginning to change their thinking about how to classify some of the dystrophies. In some cases, a type of muscular dystrophy that page 4 looked like it might be one disease has been found to be several different diseases, caused by several different gene defects. In other cases, diseases that looked different have been found to be one disease wrth variations in severity.
There is no specific treatment for any of the forms of Muscular Dystrophy; however, physical therapy, occupational therapy, corrective orthopedic surgery, pacemakers, and numerous other medical deVices and procedures have been used to treat MD patients. The prognosis of this disease varies according to the type of MD and the progression of the disorder. Some cases may be mild and veiy slowly progressive, with normal lifespan, while other cases may have more marked progression of muscle weakness, and cause disability and mobility problems, Life expectancy may depend on the degree of progression and late respiratory deficit. Muscular Dystrophies are caused by flaws in muscle protein genes. Each cell in the human body contains tens of thousands of genes. Each gene is a string of the chemical DNA and is the “code” for a protein. Although Muscular Dystrophy is generally inherited, in some cases no family history of the disease may exist.
A doctor makes a diagnosis by evaluating the patient‘s medical history and by performing a thorough physical examination. Page 5 Essential to diagnosis are details about when weakness first appeared, its severity, and which muscles are affected. Diagnostic tests may also be used to help the doctor distinguish between different forms of muscular dystrophy, or between muscular dystrophy and other disorders of muscles or nerves. There are several common dragnostic tests that aid in the diagnosis process. Studying a small piece of muscle tissue taken from an individual during a muscle biopsy can sometimes tell a physician whether a disorder is muscular dystrophy and which form of the disease it is. Another diagnostic test measures nerve conduction velocity (NCV). During this test, electrical impulses are sent down the nerves of the arms and legs. By measuring the speed of these impulses with electrodes placed on the skin, the doctor can determine whether the nerves are functioning normally.
An electromyogram (EMG) may also be used for diagnostic testing. To do this test, small electrodes are put into the muscle, which allows the doctor to measure the electrical impulses coming from the muscle. Blood enzyme tests are helpful because degenerating muscles become “leaky.” They leak enzymes (proteins that speed chemical reactions), which can then be detected in the blood. The presence of these enzymes in the blood at higher than normal page 6 levels may be a sign of muscular dystrophy, One such enzyme is creatine kinase, or CKThe CK level is elevated in many forms of muscular dystrophy. some forms resulting in a higher level than others (98). One of the most common types of Muscular Dystrophy is Duchenne, a rare inherited neuromuscular disorder. This disease, also known as Pseudohypertrophic Muscular Dystrophy, is characterized by rapid muscle degeneration during childhood.
Since the disease is a recessive trait linked to the x chromosome, almost all of the affected children are male. This disease, known to result from a defect in a single important protein in muscle fibers called dystrophin, is named after Dr. Duchenne de Boulogne who worked in Paris in the mid-19th century and was one of the first people to study the muscular dystrophies. Most boys affected by Duchenne develop the first signs of difficulty in walking at the age of l to 3 years: by about 8 lo 11 years (rarely earlier or a little later) they become unable to walk (www.aura.com). Unfortunately, like other forms of Muscular Dystrophy, no cure has yet been discovered for DMD. Much can be done to help limit the effects of the muscular dystrophy but no treatment is page 7 known which affects the actual loss of muscle cells. Intensive research to find a cure has been carried on for many years.
The discovery of dystrophin in 1987 has given scientists a practical starting point in their search for away to influence the genetic fault or to find a way around it. However, no one can predict how soon this may be achieved or which of the new Ideas which are constantly being tested Will prove worthwhile. Reliable tests for diagnosing Duchenne are available once it has become apparent that a patient may be afflicted by this relatively rare condition. All affected boys have very abnormally high levels of an enzyme called creatine kinase in their blood. However, there are other rare causes of a positive creatine test, so for a specific diagnOSIs in families with no previously affected member, a muscle biopsy is generally regarded as essential. Only specialized hospital departments have the faCilities for domg muscle biopsies of a high enough quality to give fully reliable results.
Recently measurement of dystrophin in muscle is being used increasingly in specialized units but it is not usually essential for the diagnosis. In addition to these procedures, a blood test can be done to examine DNA. which is the chemical material of which genes are made. In about two thirds of page 8 boys with Duchenne muscular dystrophy a deletion from the Duchenne gene can be identified by this test, but this is generally of more use in genetic counseling for the family than in the initial diagnosis. Duchenne muscular dystrophy is caused by an X-Iinked gene (that is, the gene is on the X chromosome; females have two such chromosomes and males only one), This means that usually only males are affected by the disease. However, presently, in almost half of all boys affected by Duchenne the faulty gene has arisen by a gene mutation. and no other member of the family carries it, But this is difficult, and sometimes impossible. to prove and can be decided only after careful expert assessment of the family. Women who carry the gene but are not affected by this disease are known as ‘carriers’.
Each subsequent son of a carrier has a 50:50 chance of being affected and each daughter has a 50:50 chance of being a carrier herself. If a boy is diagnosed With Duchenne Muscular Dystrophy, those members of the family who are at risk of being carriers must seek genetic adwce and appropriate tests as an important medical precaution .A small number of female carriers of the gene have a mild degree of muscle weakness page 9 themselves and are then known as “manifesting carriers” (www,mdac.ca), At the present time, It is possibly for detection of Duchenne Muscular Dystrophy to by made while a fetus is still in utero, This detection procedure is possible when DNA studies. performed beforehand on all the necessary members of the family, give precise information which allows the status of the unborn baby to be identified. His own DNA is studied in a chorion villus biopsy.
This test is performed on a tiny piece of the developing placenta, usually at about the 10th week of pregnancy. If this procedure cannot be performed, the best that can be done is verification of whether the fetus is male or female by the chorion vrllus biopsy at 10 weeks, or by amniocentesis at about 16 weeks. However’ this does not show whether a male is affected or not. Minimal medical help is usually needed in the early days after diagnosis. Active exercise is important but not necessarily with medical supervision. Obesity is a common problem in later years, while muscle wastes into fat, and is best prevented by establishing sensible eating habits as early as possible. As years go by, and the disease progresses, regular supervision Will become page 10 increasingly important.
Early identification of contractures (shortening of muscles) and Spinal curvature will allow these to be treated more effectively, and preventive treatment may be recommended. Special equipment may be prescribed to maintain independence (www.mdusaorg). Although the current life span for a male suffering from Duchenne Muscular Dystrophy is currently only from late teens to early twenties, new medical advancements are providing prospects for an optimistic future. Respiratory and cardiac procedures are making it possible to not only increase life span, but also to increase the quality of life for those wrth Muscular Dystrophy. In addition to treatments, new genetic findings are bringing scientists closer to a cure, a dream of many which wrll hopefully someday be realized.