Causes/Genetics

Because females are almost exclusively affected by RS, many researchers suggest that the disorder is due to mutation in a gene transmitted as an x-linked dominant trait. However, in most females with RS, the disorder appears to result from new (sporadic) changes of the RS gene. Yet there have been some instances in which the disorder has affected more than one female family member, particularly sisters or identical twins. In addition, there are some affected families in which RS has occurred in more than one generation (e.g., a maternal aunt and niece).

In 80% of females with RS, the syndrome is caused by mutations of a gene known as MECP2, which is thought to be critical in brain development. The gene is located on the long arm (q) of chromosome X (Xq28).

The protein that is regulated by this gene (methyl-CpG-binding protein 2 [MeCP2]) helps to control the expression of other genes or essentially "silence" other genes at certain critical times in development. Accordingly, in infants and children with RS, certain genes may remain active at inappropriate times of development, affecting the proper functioning of nerve cells, causing impaired or arrested brain development, and ultimately leading to the symptoms and findings associated with RS.

Some researchers have speculated that RS may also result from mutations of mitochondrial DNA (mtDNA). Mitochondria are relatively small, rod-like structures inside of cells. They are located outside the nucleus and serve as a major source of cellular energy regulation and production. Mitochondria contain their own unique DNA (deoxyribonucleic acid). Specific mtDNA mutations have been identified in some RS patients. However, to date, such findings have not indicated a primary role for mtDNA mutations as a cause of RS. Further research is necessary to determine whether mitochondrial abnormalities may be a causative factor in some patients.

	Pathophysiology