Muscular dystrophy is a group of genetic disorders characterized by progressive muscle weakness and degeneration. The way muscular dystrophy is inherited depends on the specific type of the disease, as different forms have distinct genetic causes and inheritance patterns. Understanding how muscular dystrophy is inherited requires a basic grasp of genetics, including how genes are passed from parents to children and how mutations in these genes affect muscle function.
At its core, muscular dystrophy results from mutations in genes that are crucial for maintaining healthy muscle fibers. These mutations disrupt the production or function of proteins needed for muscle strength and repair. Because these genes are inherited, the disease often runs in families, but the exact pattern of inheritance varies.
There are several common inheritance patterns for muscular dystrophy:
1. **X-linked Recessive Inheritance**
This is the most common pattern seen in Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). These diseases primarily affect males because the mutated gene is located on the X chromosome. Males have one X and one Y chromosome, so if their single X chromosome carries the mutation, they will develop the disease. Females have two X chromosomes, so if one is mutated, the other can often compensate, making them carriers who usually do not show symptoms or have milder symptoms. A mother who is a carrier has a 50% chance of passing the mutated gene to her sons (who will be affected) and a 50% chance of passing it to her daughters (who will be carriers).
2. **Autosomal Dominant Inheritance**
In this pattern, only one copy of the mutated gene (from either parent) is enough to cause the disease. Facioscapulohumeral muscular dystrophy (FSHD) is an example. Here, a mutation leads to abnormal activation of a gene called DUX4, which is normally turned off in muscle tissue. If a parent has the mutation, each child has a 50% chance of inheriting the disease. This form can sometimes appear in families with no prior history due to new mutations.
3. **Autosomal Recessive Inheritance**
For some types, such as certain limb-girdle muscular dystrophies (LGMD), a child must inherit two copies of the mutated gene—one from each parent—to develop the disease. Parents who each carry one mutated gene are typically unaffected carriers. When both parents are carriers, there is a 25% chance with each pregnancy that the child will have the disease, a 50% chance the child will be a carrier, and a 25% chance the child will inherit two normal genes.
4. **Other Complex or Rare Patterns**
Some muscular dystrophies involve more complicated genetic mechanisms. For example, myotonic dystrophy involves an unusual mutation where DNA sequences repeat many times, disrupting normal gene function. The severity and inheritance can vary widely depending on the number of repeats and other genetic factors.
The inheritance of muscular dystrophy is also influenced by specific genetic features such as:
– **Gene Mutations and Deletions:** Many muscular dystrophies are caused by mutations that delete or alter parts of a gene, leading to missing or dysfunctional proteins. For example, Duchenne muscular dystrophy is caused by mutations in the dystrophin gene, which is essential for muscle fiber stability.
– **Epigenetic Changes:** In some types like FSHD, the problem arises not just from a mutation but from changes in how the gene is regulated, such as hypomethylation, which leads to inappropriate gene activation.
– **Haplotypes and Genetic Variants:** Certain genetic backgrounds or haplotypes can influence whether a mutation causes disease. For instance, in FSHD, a specific variant of chromosome 4 (called 4qA) is necessary for the disease to manifest.
Because muscular dystrophies are inherited, genetic testing and family history are important tools for diagnosis and counseling
