What is Rett Syndrome?

Rett Syndrome (RTT) is a disorder of brain development that is diagnosed almost exclusively in girls. Although the genetic mutation is present at birth, symptoms, which include loss of language and severe motor deficits, do not manifest themselves until the child’s second year. The disorder is named after an Austrian physician, Dr. Andreas Rett, who first recognized the disorder as its own unique syndrome.  RTT strikes randomly and knows no ethnic, racial or socio-economic boundaries.
RTT is caused by a defect in a gene, called MECP2, located on the X chromosome. With a prevalence rate hypothesized to be 1 in 10,000 females, RTT is the leading genetic cause of severe impairment in girls. It is also the only autism spectrum disorder with a known genetic cause.

In the world of rare disorders (defined as disorders affecting less than 200,000 individuals in the U.S.) RTT is a common disorder. Furthermore, as testing for RTT becomes more routine and the true extent of its broad spectrum of symptoms is better understood we expect the prevalence rate to increase. It is probable that mutations in MECP2 will prove to be more common then previously expected.

The identification of the gene in late 1999 in the lab of Dr. Huda Zoghbi at Baylor College of Medicine, after a fifteen-year search, was a crucial breakthrough that has catapulted the RTT research field into the scientific limelight. Today, there are hundreds of laboratories around the world studying RTT.

In recent years we have learned that mutations in MECP2 can lead to a variety of disorders besides RTT, including autism, learning disability, schizophrenia and a host of mental disorders. Recently, it was found that boys with a genetic error that results in two MECP2 genes (known as duplication) rather than one presented with severe mental retardation.  It appears that too much MECP2 is just as detrimental as too little.

Classic RTT is diagnosed clinically using the criteria on the following page. Testing positive for an MECP2 mutation confirms the clinical diagnosis. However, a clinical diagnosis for RTT can occur in the absence of an MECP2 mutation.

  Diagnostic Criteria

• Period of apparent normal development until 6-18 months (some girls have an earlier onset of RTT symptoms and therefore have no normal period of development).
• Normal head circumference at birth followed by slowing of the rate of head growth (there is a subset of girls whose rate of head growth does not decelerate).
• Loss of verbal language.
• Purposeful hand use is replaced by stereotypical hand movements (these can include a multitude of hand movements, some girls have movements unique to them or none at all).
• If able to walk the gait is usually wide-based and stiff
• Shakiness of torso and/or limbs, especially when upset.

Supportive Criteria

• Breathing pattern irregularities which include hyperventilation, breath holding, apnea, air swallowing
• EEG abnormalities
• Seizures
• Scoliosis
• Teeth grinding (bruxism)
• Gastrointestinal issues which may include reflux, constipation, poor nutrient absorption
• Growth retardation and decreased body fat and muscle mass
• Biting/Chewing/Swallowing difficulties
• Poor circulation to legs and feet
• Decreased mobility with age
• Muscle rigidity/spasticity/joint contractures
• Small feet (mottled and purplish
• Abnormal sleep patterns
• Irritability and agitation

Typical RTT vs. Atypical RTT

While individuals with typical or classic RTT meet the diagnostic criteria listed above there are also cases of atypical RTT which include:

• Congenital Onset RTT: developmental delay is noticed shortly after birth with no early normal development or severe seizures in early infancy impairing early development.
• Late Onset RTT: signs are delayed beyond the typical 18 month onset, in some cases to age 10 years or more.
• Preserved Speech RTT: milder features are seen