Genetics
What causes muscular dystrophy?
To understand how muscular dystrophy and other neuromuscular disorders occur, it helps to understand a bit about genetics. Genes are the basic functional units of heredity that let the cells and tissue of the body know what specialized functions they will perform. There are approximately 80,000 individual genes located on the 46 chromosomes inside each cell within the human body.
Every gene carries the code required to direct the cell to make a specific protein - the molecules that carry out all of the work of the cell. The proteins synthesized by the genes are responsible for all structure and functions of living cells from eye color to muscle function. Each form of muscular dystrophy is caused by an error in a specific gene associated with muscle function.
How do gene mutations cause muscular dystrophy?
Muscle tissue is made up of long muscle fibers. Each fiber is actually an elongated cell that is made up of many individual cells that have fused. The genes in the nuclei of these cells direct the production of the proteins that carry out the function of muscle tissue (muscle contraction). Different types of muscular dystrophy are due to errors in different proteins, determined by different genes. Lack of dystrophin causes breakdown of muscle fibers that leads to a specific clinical pattern that has been called Duchenne muscular dystrophy.
Becker muscular dystrophy is another muscular dystrophy where there is insufficient production of dystrophin, but to a less severe degree (dystrophin is still produced but it is either altered or available in abnormally low amounts). The clinical picture is closely related to Duchenne, but symptoms are less severe and progression of weakness is slower.
Where do the mutated genes come from?
When a baby is formed, he/she receives 23 chromosomes from each parent, for a total of 46 chromosomes (23 pairs). Normally, each pair of chromosomes carries genes for the same trait. 22 pairs of the chromosomes are called autosomal chromosomes, which simply mean that they are identical in both males and females. The 23rd chromosomal pair is known as the sex chromosome, and it is here that the sex of the unborn child is determined. Each female carries two X chromosomes and each male carries one X and one Y chromosome. An unborn child will receive one X chromosome from the mother and either an X or a Y from the father. If an X is received from each parent, the child will be a girl (XX). If a Y is received from the father, then the child will be a boy (XY). Genes are found packed together on these chromosomes. Each gene has a precise location on one of them. For reasons that are only partly understood, one or more genes may become flawed or lost, and a serious disorder may result.
Depending on the type of muscular dystrophy, the faulty or missing genes may be inherited. Also, the way that the disorder is inherited will vary from disease to disease. There are three main patterns of inheritance: autosomal dominant and autosomal recessive, which relate to transmission of traits determined by genes on the autosomal chromosomes, and X-linked recessive, which pertains to traits determined by genes found on the X chromosomes.
What is autosomal dominant inheritance?
Disorders that follow an autosomal dominant inheritance pattern typically appear in every generation, without skips. Autosomal refers to the fact that the genetic error can occur on any one of the 46 chromosomes in each cell in the human body, except the two sex chromosomes. Dominant refers to the fact that it is necessary for only one parent to transmit the abnormal gene for the disorder to be transmitted. The other parent transmits a normal gene. Thus, the disorder can be inherited from either parent and each child of an affected parent has a 50% chance of being affected. The severity of the disorder and the age of onset can vary from person to person. Examples of disorders with this type of inheritance pattern are facioscapulohumeral dystrophy and myotonic dystrophy.
What is autosomal recessive inheritance?
In autosomal recessive inheritance, the disorder usually appears in only one generation, and there is typically no previous family history of the disorder. Both parents must be carriers of the faulty gene. A carrier harbors the faulty gene, but usually show no symptoms. Recessive refers to the fact that the child needs to inherit the faulty gene from both parents in order to have the disease. Children of either sex can be affected. With each pregnancy, there is a 25% chance the child will receive a faulty gene from each parent and thus, will be affected with the disorder. If the child inherits a faulty gene from one parent only, he/she will be a carrier of the disorder, but will probably show no symptoms. There is a 50% chance the child will be a carrier. An example of an autosomal recessively inherited form of muscular dystrophy is limb-girdle muscular dystrophy.
What is x-linked recessive inheritance?
In an X-linked mode of transmission, the faulty gene is carried on one of the X chromosomes that help determine the sex of a child. Their mothers pass on the disorder to male children. When the mother is a carrier, boys have a 50% chance of being affected, while girls have a 50% chance of being carriers. Should a man with an X-linked dystrophy have children, none of his sons will be affected, while all of his daughters will be carriers. This is because his sons receive the Y chromosome, which is normal, and his daughters receive the affected X chromosome. Examples of X-linked recessive inherited forms of muscular dystrophy are Duchenne and Becker muscular dystrophy.
What is gene mutation?
A gene mutation is a spontaneous or inherited change in a gene that allows an altered characteristic or disorder to appear. New gene mutations are unpredictable, occurring at random within the population. It has been shown that in approximately one third of boys with Duchenne muscular dystrophy, the disease appears as a result of a spontaneous gene mutation. In fact, gene mutations are not uncommon in some other serious early onset forms of muscular dystrophy passed on via autosomal dominant or X-linked inheritance pattern.
