Genetics of Facioscapulohumeral Muscular Dystrophy
Facioscapulohumeral muscular dystrophy (FSHD) is a genetic disorder that affects the muscles, causing progressive weakness and loss of muscle mass. It is one of the most common forms of muscular dystrophy, affecting approximately 1 in 20,000 people worldwide. FSHD is a complex genetic disease, with both genetic and environmental factors playing a role in its development. In this article, we will explore the genetic basis of FSHD and how it is inherited in families.
Genetic basis of FSHD
FSHD is caused by mutations in the DUX4 gene, which is located on chromosome 4. The DUX4 gene codes for a protein that plays a role in muscle development and function. In individuals with FSHD, the DUX4 gene is abnormally activated, leading to the production of toxic levels of the DUX4 protein in muscle cells. This toxic protein damages the muscle cells, leading to muscle weakness and atrophy.
There are two types of FSHD: FSHD1 and FSHD2. FSHD1 is the most common form of the disease, accounting for around 95% of cases. FSHD1 is caused by a deletion in a region of chromosome 4 called the D4Z4 repeat, which leads to the abnormal activation of the DUX4 gene. FSHD2, on the other hand, is caused by mutations in the SMCHD1 gene, which is involved in regulating the expression of the DUX4 gene. Both FSHD1 and FSHD2 result in the abnormal activation of the DUX4 gene and the production of toxic levels of the DUX4 protein.
Inheritance of FSHD
FSHD is inherited in an autosomal dominant pattern, which means that only one copy of the mutated gene is needed to develop the disease. In most cases, individuals with FSHD inherit the mutated gene from one of their parents. However, in around 30% of cases, the mutation occurs spontaneously, with no family history of the disease.
When a person with FSHD has children, each child has a 50% chance of inheriting the mutated gene and developing the disease. This means that FSHD can be passed down through multiple generations within a family. It is important for individuals with a family history of FSHD to undergo genetic testing and counseling to understand their risk of passing the disease on to their children.
Genetic testing for FSHD
Genetic testing is available for FSHD and can help confirm a diagnosis in individuals with symptoms of the disease. The most common test for FSHD1 is the D4Z4 repeat contraction analysis, which looks for deletions in the D4Z4 repeat region on chromosome 4. For FSHD2, genetic testing for mutations in the SMCHD1 gene is available.
Genetic testing can also be used for carrier testing in individuals with a family history of FSHD. Carrier testing can determine if a person carries the mutated gene for FSHD, even if they do not have symptoms of the disease. This information can be valuable for family planning and reproductive decision-making.
In conclusion, FSHD is a genetic disorder caused by mutations in the DUX4 gene, leading to the production of toxic levels of the DUX4 protein in muscle cells. FSHD is inherited in an autosomal dominant pattern, with a 50% chance of passing the mutated gene on to each child. Genetic testing is available for FSHD and can help confirm a diagnosis and determine the risk of passing the disease on to future generations. With advances in genetic research and testing, there is hope for better understanding and treatment of FSHD in the future.
