Facioscapulohumeral Muscular Dystrophy (FSH, FSHD)
FSHD is an inherited neuromuscular disorder that causes weakness most prominently of the muscles in the face, shoulder blades, and upper arms. It often progresses to cause widespread muscle weakness, as well as loss of hearing.
The region of our chromosomes that causes FSHD contains a section with multiple identical units of DNA called D4Z4 repeats. Each repeat contains a copy of a gene called DUX4. This gene is used during fetal development, but in adulthood, the DNA in this region is normally “condensed,” or packed tightly together, which prevents the cellular machinery from reading the DUX4 gene. As a result, no protein is made from it once fetal development is completed.
In FSHD, multiple D4Z4 units are lost, which de-condenses the DNA and reactivates the DUX4 gene, allowing aberrant production of the DUX4 protein. Many FSHD researchers now believe that elevation of DUX4 protein causes the symptoms of FSHD.
In about 5 percent of people with FSHD, the D4Z4 region is of normal length. In these individuals, mutations in a different gene, called SMCHD1, cause the DNA in the vicinity of the D4Z4 repeats to be opened up, allowing the DUX4 gene to be read and protein to be produced.
A mutation from one parent is sufficient to cause FSHD
FSHD is inherited in an autosomal dominant pattern, meaning it only takes one such mutation (from one parent) to cause the disorder. This altered piece of DNA also can occur spontaneously in a child as he or she develops in the womb.
FSHD can affect either males or females. In a small number of people with FSHD, the usual chromosome 4 mutation can’t be identified. In most affected people, it can be, with genetic testing. (For more on this, see Diagnosis.)
FSHD is one of many genetic disorders in which germ line mosaicism is believed to occur. Germ line refers to egg or sperm cells. In this phenomenon, some sperm or egg cells in a parent carry a particular mutation.
In families with more than one child with FSHD but no previous family history, it’s likely that one parent has germ line mosaicism and that affected children were conceived with egg or sperm cells carrying the FSHD mutation. In these situations, the parents have no symptoms, and, if their blood cells are tested, they don’t show the mutation.
For help in understanding your family’s specific situation and planning for future children, it’s best to meet with a genetic counselor.