Muscular dystrophy and many related neuromuscular disorders are genetic diseases caused by errors in genes associated with muscle function.
Genes are the basic functional units of heredity. Each gene contains the code to make a message to tell the cells how to make a particular product such as a protein. The proteins are responsible for all living cells’ structures and functions – from eye colour to muscle movement. If a gene is mutated, the protein will be damaged, faulty or even non-existent.
We all have variations in our DNA which is why we are unique. Very rarely, these changes make a gene faulty and can result in a genetic condition. These variations which make a gene faulty are called mutations.
Gene mutations occur in two ways: they can be inherited from a parent or acquired during a person’s lifetime (“spontaneous” mutation). Spontaneous mutations occurs when genes, which are tightly packed together to form chromosomes, become flawed or lost during cell division and creation of new cells.
Our bodies are made up of millions of cells. In each of these cells, we have 46 chromosomes arranged in 23 pairs. One of each of these pairs is passed down from our mother and the other from our father. The first 22 pairs of chromosomes, numbered 1 to 22, are called autosomes. The term autosomal inheritance refers to genes on these any one of these 44 chromosomes.
The 23rd chromosomal pair, known as the sex chromosome, determines the sex of the child. Children receive one X chromosome from their mother, and either an X or a Y from their father. If an X is received from each parent, the child will be female (XX). If a Y is received from the father, the child will be male (XY).
There are three main patterns of inheritance:
Dominant – the gene is expressed when one copy (from either parent) is inherited.
Recessive – the gene is expressed when two copies (one from each parent) are inherited.
X-linked – relating to genes carried on the X chromosome.
In autosomal dominant inheritance, only one parent needs to transmit the mutated gene for the disorder to be inherited. Even though the matching gene from the other parent is unaffected, the faulty gene dominates.
If a person affected with an autosomal dominant disorder decides to have children, each offspring has a 50% chance of inheriting the faulty gene and developing the disorder. Children who do not inherit the affected gene will not develop or pass the disorder to their offspring.
Autosomal dominant disorders typically appear in every generation without skips. Examples of autosomal dominant disorders include facioscapulohumeral dystrophy and myotonic dystrophy.
In autosomal recessive inheritance, both parents must be carriers of the faulty gene for their child to inherit the condition. A carrier harbors the faulty gene, but usually shows no symptoms. When a mutation is recessive, it can exist in a person without showing any symptoms so long as their other copy of the same gene is healthy. The unaffected gene masks the mutation. However, if a child inherits two copies of the mutated gene, there is no healthy alternative to block the faulty gene out, and so the symptoms manifest themselves.
If both parents have one copy of the mutated gene, with each pregnancy, there is a 25% chance the child will receive a faulty gene from each parent and thus be affected by the disorder. If the child inherits a faulty gene from one parent only, he or she will be a carrier of the disorder.
Autosomal recessive disorders typically appear when there is no known family history of the disorder. An example of an autosomal recessive neuromuscular disorder is Spinal Muscular Atrophy.
In an X-linked mutation, the faulty gene is carried on the X chromosome. Females carry two X chromosomes, and males carry one X and one Y chromosome. Variations in genes on the X chromosome are more commonly ‘recessive’.
If a girl inherits a faulty X-linked gene, the healthy gene on their other X chromosome blocks it out, and the disease does not manifest itself. Females can be carriers and pass the faulty gene to their offspring. Males, however, have no ‘back-up’ working copy and so will generally be affected by the condition if they have an X-linked faulty gene.
The chance that a child will inherit an X-linked recessive condition in every pregnancy is different for sons and daughters and depends on whether the mother or father has the faulty gene:
Examples of X-linked recessive disorders include Duchenne and Becker muscular dystrophy. It is interesting to note that not all cases are inherited – in approximately one third of males with Duchenne muscular dystrophy, the disorder appears as a result of a “spontaneous” gene mutation.