How is Rett Syndrome Diagnosed?

Diagnosis of Rett syndrome is based upon clinical criteria that were revised in 2010. How Rett syndrome manifests itself and progresses varies from child to child. A clinician should consider Rett syndrome when slowing of head growth is observed after birth. In most cases, the correct diagnosis can be made through a blood test(s) to identify the mutation of the MECP2 gene. But since the MECP2 mutation can also be found with other disorders, this finding alone is not enough to make a conclusive diagnosis of Rett syndrome. Additionally some children with Rett syndrome do not have the MECP2 mutation. Diagnosis requires either a molecular diagnosis of the mutation (a DNA test), satisfaction of the diagnostic criteria (this is a clinical diagnosis, secured on the basis of observable signs and symptoms listed below), or both.

There are specific diagnostic criteria for typical/classical and for atypical/variant Rett syndrome. Both require that the child have had a period of regression in developmental skills followed by stabilization and/or improvements. A case of classical Rett syndrome will have all of the main criteria while those with atypical Rett syndrome may only have some (2 out of 4). Main criteria are listed below. For diagnosis of atypical Rett syndrome, at least 5 supportive criteria (listed below) must also be present.  

The following exclude a diagnosis of classical Rett but may be present in atypical Rett syndrome: Brain injury due to trauma, neurometabolic disease, severe infection causing neurologic problems or grossly abnormal development in the first 6 months of life.  

 Main Criteria:

  • Partial or complete loss of acquired purposeful hand skills
  • Partial or complete loss of acquired spoken language
  • Gait abnormalities
  • Stereotypic hand movements such as wringing, squeezing, clapping, tapping, mouthing or hand-washing movements

Supportive Criteria:

  • Breathing disturbances when awake
  • Tooth grinding when awake
  • Impaired sleep
  • Abnormal muscle tone
  • Peripheral vasomotor disturbances
  • Growth retardation
  • Small cold hands and feet
  • Inappropriate laughing/screaming spells
  • Diminished sensitivity to pain
  • Intense eye communication and eye-pointing behavior

If the diagnosis of Rett syndrome is suspected, a blood test looking for the mutation on the X chromosome of the gene called MECP2 should be obtained. These tests are able to confirm the syndrome in up to 80 percent of all cases. Children who do not have the MECP2 mutation may be diagnosed with classical or variant Rett syndrome based upon meeting the specific diagnostic criteria above and testing for other genetic changes may be recommended in some. Variant forms of Rett often have more preserved speech and/or motor abilities. There are also variant forms with congenital onset, infantile seizures and with late onset of regression at preschool or school age.


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International Rett Syndrome Foundation