Rett syndrome is a genetic condition that affects the grey matter in the brain, leading to severe physical and mental disability. The condition affects one in 10,000 to 12,000 females by the age of 12 years and is caused by a mutation in the MECP2 gene on the X chromosome.
This gene codes for the MeCP2 protein, which is essential for the normal development of nerve cells in the brain. Rett syndrome rarely affects males, but may be seen in males who are born with more than one X chromosome (XXY configuration), a condition referred to as Klinefelter’s syndrome.
If males are born with a mutation in MECP2 on their only X chromosome, the condition is extremely severe, causing encephalopathy and often death in early infanthood.
This condition is difficult to diagnose before the age of six months, when children appear to have a normal appearance and any developmental abnormalities tend to be subtle. Infants with this condition are not normally diagnosed until 6 to 18 months, when spontaneous limb movements and poor coordination become noticeable.
This first stage of the disease is followed by the regression stage which usually begins between the ages of one and four years. The child starts to develop severe problems and loses the ability to communicate, learn and coordinate their movements. Symptoms include extreme distress, unsteadiness while moving around, social withdrawal, lack of eye contact, difficulty sleeping, difficulty eating and small head size.
The third stage of disease usually begins between two and ten years of age and is mainly characterized by difficulty moving around, epilepsy, irregular breathing and arrhythmia. However, some symptoms may also start to improve during the third stage, with the child possibly becoming less irritable, more alert and developing more of an interest in their surroundings and the people around them. There may also be an improvement in walking ability. This is the stage of disease that girls stay in for the majority of their lives.
During stage four of the disease, the main symptoms are bending of the spine to one side (scoliosis), spasticity (particularly in the legs) and inability to walk. Although some girls may retain some control over their hand movements and ability to walk and communicate, the majority become completely depended on care, which they require 24 hours. Conditions such as arrhythmia can significantly shorten lifespan but many women do survive into middle age and older.
Reviewed by Sally Robertson, BSc