Muscular Dystrophy 2 Essay Research Paper What

Muscular Dystrophy 2 Essay, Research Paper What is Muscular Dystrophy? The muscular dystrophies are a heterogeneous group of genetic musclular diseases, which have three features in common: they are hereditary, they are progressive (ie get worse over time) and each produces a characteristic selective pattern of weakness of muscle groups. (Engel 1994)

Muscular Dystrophy 2 Essay, Research Paper

What is Muscular Dystrophy?

The muscular dystrophies are a heterogeneous group of genetic musclular diseases, which have three features in common: they are hereditary, they are progressive (ie get worse over time) and each produces a characteristic selective pattern of weakness of muscle groups. (Engel 1994)

There are a number of such diseases:

Duchenne muscle dystrophy (DMD)

Becker type

Emery-Dreifuss type

Facioscapulohumeral type

Limb-girdle muscular dystrophies

Congenital muscular dystrophies

Severe childhood autosomal recessive muscular dystrophy (SCARMD)

Ocular Muscular Dystrophy

Oculopharyngeal type

Distal type

Muscular dystrophies are by definition hereditary which means that they are of genetic cause. They are due to a mistake in the genetic plan, which is put together when an individual is conceived.

There are three types of inheritance causing muscular dystrophies, called X-linked inheritance, autosomal inheritance and autosomal recessive inheritance. X-lined conditions such as Duchenne and Becker muscular dystrophies affect only males with rare exceptions. Autosomal dominant conditions, such as facioscapulohumeral and myotonic dystrophies, are transmitted from one generation to the next and a typical family tree will show several generations and multiply branches of a family having affected people. Autosomal recessive conditions, like most families with limb girdle muscular dystrophy, seldom affect more than one generation or more than one branch of the family. (Serratrice 1984)

The most common and severe types of muscular dystrophy are called Duchenne Muscular Dystrophy (DMD), after the French neurologist who first described it in 1861 and Becker muscular dystrophy (BMD). These muscle-wasting disorders have no known cure, and no medication has yet been shown to be of value in arresting the disease. Although Duchenne and Becker dystrophies are a serious disease, there is little or no pain associated with it. There is no effect on sensations. The bladder, bowels and sexual function develop and continue to function effectively. (Adams 1994)

As a result, this essay will deal only with the Duchenne type muscular dystrophy (DMD) and Becker type muscular dystrophy (BMD).

DMD and BMD cause similar patterns of weakness and disability and are inherited in the same way. Weakness and disability are more severe in DMD than in BMD. Becker dystrophy is like a less severe form of Duchenne dystrophy.


DMD affects only males, with rare exceptions. Unless a boy with DMD is known to be at risk because of his family history, he is unlikely to be diagnosed before the age of 2 or 3 years. Most boys with DMD walk alone at a later age than average. Then the parents are likely to be worried about something unusual in the way he walks, about frequent falling or about difficulty rising from the ground or difficulty going up steps. Less often, concern arises because of intellectual handicap (”mental retardation”). Although intellectual handicap affects only a minority of boys with DMD, it is more frequent than in other children. (Beggs 1990)

Among the first symptoms of DMD are difficulties in climbing stairs and rising to a standing position, a waddling gait, and frequent falls. The wasting of muscles usually begins in the lower trunk and calves, progresses to the upper trunk and arms, and eventually involves all of the major muscle groups. DMD is sometimes referred to as pseudohypertrophic muscular dystrophy because it characteristically results in a seeming enlargement of the calf muscles, which look abnormally big because fat and connective tissue have replaced degenerating muscle fibres. (Engel 1994)


BMD is less severely disabling then DMD. An arbitrary means of distinguishing the two disorders depends on whether the affected person can still walk at age 16 years. Muscle biopsy tends to show more or less severe changes, related to the severity of disability.

Since the discovery that dystrophin is defective in DMD and BMD, but more severely defective in DMD, examination of dystrophin in muscle biopsy samples can be used to distinguish them. (Franzini 1991)

Are other muscular dystrophies difficult to distinguish from BMD?

Limb-girdle muscular dystrophies (LGMD), which are most often of autosomal recessive inheritance, may be difficult or impossible to distinguish from BMD which is X-linked recessive. The mode of inheritance and therefore the diagnosis may be revealed by the family tree or by blood tests (SCK) revealing carrier status in female relatives in the case of BMD.

The test is a measurement of the amount of a chemical, called creatine kinase, in the blood. It is a serum creatine kinase (SCK) measurement. (Franzini 1994)

Creatine Kinase is an important chemical in muscle fibres and there is normally a small amount of it in the blood serum. (Serum is yellow fluid, which is left when the blood cells have been allowed to clot and have been removed). In DMD and BMD, creatine kinase leaks out of the muscle fibres and is therefore found in greatly increased amounts in the serum. In young boys with DMD, the SCK level is nearly always at least 5 times as high as the maximum for unaffected people. It is sometimes 50 to 100 times as high.

However the conclusive test to distinguish BMD and LGMD is the examination of dystrophin on the muscle biopsy specimen. (Beggs 1990) Muscle biopsy Muscle from patients with muscular dystrophy looks different from normal muscle when it is seen under a microscope. The small piece of muscle that is removed during the biopsy is cut into very thin slices, stained with a series of special dyes to show the different types of muscle fibres, and studied by a pathologist.

Other tests include, Electromyography (EMG). When muscles contract (shorten) there is electricity flowing through the muscle tissue. An abnormal muscle has an abnormal pattern of electricity that can be recognized and recorded using special equipment. An EMG test involves putting a small needle through the skin into a muscle and recording the pattern of electricity in the muscle when it is contracting and a DNA blood test to analysis the X chromosome (PCR–polymerase chain reaction ) (Beggs 1990)

Recently it was shown that DMD and BMD are due to defects of the same gene. The normal function of the gene is to enable muscle fibres to make a particular chemical substance, a protein called dystrophin. Muscle fibres in people affected with DMD are extremely deficient in dystrophin, in BMD the deficiency is less severe. (Engel 1994)


Like the other muscular dystrophies, DMD and BMD are inherited – it is a genetic condition. DMD and BMD are due to defects in the same gene, which is now known to be the dystrophin gene, on the X chromosome. They are inherited as X-linked recessive diseases so females carry the defective gene that causes the disorder, but the disease almost exclusively affects males. Unlike most of the other dystrophies, they are transmitted by an altered gene on the X chromosome in an “X-linked” (or “sex-linked”) recessive pattern of inheritance. (Fleckenstein 1996) This means :

Only males are affected, with rare exceptions.

Female relatives of affected males may be carriers.

The mothers of affected males, in families with more than one affected male, are carriers.

The mothers of affected males with no affected relatives are not always carriers, because their sons may have been affected by new mutations.

The son of a carrier has a 50% probability of being affected.

The daughter of a carrier has a 50% probability of being a carrier.

The sons of an affected male are all unaffected; his daughters are all carriers.

Genes and Chromosomes

All of our inborn traits, from the colour of our eyes to our blood types, are determined by our genes – chemical segments of information that are the basic units of hereditary. Genes are carried on the rod-like structures known as chromosomes, which are found in every cell nucleus in our bodies. Except for sperm and egg cells, which contain twenty-three chromosomes, human cells have forty-six chromosomes, half of them contributed by the mother and half of them by the father. Normally, forty-four of the forty-six chromosomes occur in pairs, with both members of a pair carrying genes for the same trait. For every trait there are two genes, one on each chromosome of a pair, in corresponding positions.

These rules apply only to traits carried on the twenty-two pairs of corresponding chromosomes known as the autosomes. With the two remaining chromosomes, the situation is different. These are the ones that determine whether an individual is male or female and therefore are known as the sex chromosomes, X and Y. In addition to the forty-four autosomes, females have a pair of X-chromosomes. males, on the other hand, do not have a matching pair of sex chromosomes; they have one X and one Y, which carry different genes. Consequently, the mother always contributes and X. The father will determine whether the child is a girl or boy by passing on either and X, which will result in a female, or a Y, which will result in a male. The defective gene in DMD and BMD is carried only on the X chromosome. (Beggs 1990)

X-Linked Recessive Inheritance

The gene for DMD and BMD is located on the X chromosome as stated previously. Since the defective gene is recessive, a female with a DMD or BMD gene on one of her two X chromosomes will not develop muscular dystrophy. The normal gene on her second X chromosome masks the effects of the defective gene. Such a woman is called a “carrier”. Male offspring, however, have only one X chromosome, and there are no equivalent genes on the Y chromosome. Consequently, in males the X-chromosome genes have no “partners”. Therefore, a male with the a DMD or BMD gene on his X chromosome will be affected with the condition because he has no normal gene to counteract the effect of the abnormal one.

Each time a DMD/BMD carrier mother has a child, there are four possible outcomes, each with an equal probability of happening. Thus, the chance of producing an affected son is one in four, or 25 %. If we breakdown the risk further according to the sex of the child, it follows that there is a 50% chance that each son will be affected. All daughters will be unaffected, but each has a 50% chance of being a carrier like her mother.

It is important to point out that unaffected sons of carrier mothers do not have the DMD/TDM gene, and therefore, cannot transmit DMD or TDM to their offspring. The same is true for those daughters of carriers who have not inherited the DMD/TDM gene. If circumstances should allow a male affected with DMD/TDM to reproduce, and if his wife was not a carrier of DMD, then all of his sons would be unaffected and free of the gene but all of his daughters would be carriers. (Franzini 1994)

A fault in a particular gene, carried on the X chromosome which is located at Xp21, leads to the formation of a faulty protein in muscle fibres. This protein, called dystrophin, is absent or severely abnormal in DMD or less abundant than normal. The function of dystrophin in the muscle fibre is not yet fully understood, but when it is abnormal the muscle fibres gradually break down and the muscles slowly become weaker. Dystrophin is a large, rod liked cytoskeletal protein which is found at the inner surface of muscle fibres. These dystrophin abnormalities in muscle provide a very good test for the diagnosis of BMD.

The gene that when mutant causes DMD and BMD is an enormous gene approximately 2300kb in size, containing at least 75 exons and large introns. Many different mutations in the gene have been characterized; at least 60% are deletions, 6% are duplications, one is a chain-termination point mutation, and the remainder are unknown. The gene is expressed primarily in muscle, but also in lesser amounts in the brain and a variety of other tissues. (Engel 1994)

The difference between the severe Duchenne and milder Becker phenotypes is accounted for by the nature of the mutation and it s effect on the reading frame of the gene. The Duchenne phenotype is usually caused by mutations that disrupt the reading frame and prevent formation of detectable amounts of dystrophin, whereas the Becker phenotype is usually the consequence of mutations that maintain the reading frame and allow production of a truncated but partially active form of dystrophin. (Adams 1994)

Active research is proceeding to try to find a way to induce the muscles to form dystrophin. Active exercises strengthen normal muscle fibres. It s important to try and keep fit and as active as possible to help prolong the onset of the disease. Any treatment, which may be found to be effective in Duchenne muscular dystrophy, would theoretically be effective also in the Becker type.


Adams, Raymond D. (1975) “Diseases of Muscle-A study in Pathology” 3rd Ed. Harper and Row Publishing New York USA

Beggs, AH. (1990) “Human Genetics” 2nd Ed. Watson and Co. Publishing Washington USA

Engel, Andrew G. (1994) “Myology” 2nd Ed. Volume 2 McGraw-Hill Inc New York USA

Fleckenstein, James L. (1996) “Muscle Imaging- In health and disease” Springer-Verlag Inc New York USA

Franzini, Clara A. (1994) “Myology” 2nd Ed. Volume 1 McGraw-Hill Inc New York USA

Serratrice, George M. (1984) “Neuromuscular Diseases” Raven Press New York USA