Rett Syndrome

Rett syndrome (RS) is a progressive neurodevelopmental disorder of childhood onset that occurs almost exclusively in females. Infants and children with RS usually appear to develop normally until about 6 to 18 months of age. They may then cease to acquire new skills and gradually or suddenly lose previously obtained skills (developmental regression), such as conscious control of the hands and the ability to vocalize most sounds or words. Acquired hand and finger use is gradually replaced by repetitive, distinctive, uncontrolled hand movements, such as hand clapping, clenching, grasping and releasing, patting, mouthing, or "washing" and wringing. In addition, the tongue may repeatedly twist or contort in ineffective chewing movements, and there may be involuntary grinding, gnashing, or clenching of the teeth (bruxism). Affected children may also develop autistic-like behaviors; an impaired ability to perform the motor movements required for coordinating walking (gait apraxia) and trunk movements; breathing irregularities during waking hours; seizures; feeding and swallowing difficulties; and growth retardation. Over time, some patients may develop increasing motor difficulties, whereas other associated symptoms may tend to stabilize or improve over time. Increasing motor difficulties may include loss of the ability to walk (although some may never have gained this ability); increasing muscle weakness; spasticity; dystonia, most often involving the legs; and/or other involuntary movements, such as myoclonus or athetosis.

RS usually appears to occur randomly for unknown reasons (sporadically) in the absence of a family history. Yet there have been some instances in which the disorder has affected more than one family member, particularly sisters or identical twins. In such cases, the disorder's mode of inheritance remains uncertain, although some researchers suggest that RS may be transmitted as an X-linked dominant trait or be due to germline mosaicism in a parent.

In some females, RS is caused by mutations of a gene known as MECP2 on chromosome X (Xq28) that is thought to be critical in brain development. The protein 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. Some researchers have speculated that RS may also result from mutations of DNA within mitochondria (mtDNA)—i.e., the relatively small, rod-like structures outside the nuclei of cells that serve as a major source of cellular energy. Although the basic underlying defect in RS is unknown, defective maturation of several neurotransmitter systems is thought to play some role. Researchers have demonstrated reduced activity of several neurotransmitters, including dopamine, norepinephrine, acetylcholine, and serotonin, in certain regions of the basal ganglia and cerebral cortex.

	Parkinson's Disease