What causes FSHD?

Muscular dystrophies are like in that they cause progressive skeletal muscle weakness, defects in the biochemical, physical and structural components of the muscles, and the loss of muscle cells and tissue. However, researchers believe that the causes of muscular dystrophies are not necessarily the same.

By going from the large (muscle) cells to the small ones (DNA), one can partially understand the cause and origin of FSHD. In association with proteins, DNA makes up our chromosomes and holds the genetic instructions for our hereditary traits. Discrete segments of DNA called genes determine specific traits. Taken together, the combination of approximately 24,000 genes makes each of us 'an original'.

FSHD is caused by a genetic defect strongly related with a deletion at the very end of chromosome 4. The actual FSHD gene(s) that causes this deletion is still unknown, but its approximate location is towards the end of chromosome 4. The specific genetic location of the FSHD deletion is 4q35in the D4Z4 region.

The size of the deletion has a relationship with the severity of the disease – patients with t he fewest repeats (the largest deletion) typically have the most severe symptoms, but it is not yet certain whether the deleted DNA contains an active gene or changes the regulation or activity of a nearby FSHD gene (a position effect). Research is ongoing in this area.

FSHD is a dominant genetic disorder, meaning that each child with parents with FSHD has a 50% chance of inheriting the disease. Sometimes, FSHD results from a new mutation. Studies show that in about 10 to 33% of all FSHD cases there is mention of a spontaneous occurrence. In about 20% of those cases it turns out that one of the parents is a patient without any apparent symptoms.

Researchers are for years now investigating the molecular connection between the deletion and FSHD, as this is the first step in finding the exact cause and – at a later stage – a cure.