Table 1

Clinical diagnostic criteria for Rett syndrome (adapted from Neul and colleagues1)

Main criteriaSupportive criteriaExclusion criteriaRequired for classic RTTRequired for variant RTT
Partial/complete loss of acquired purposeful hand skillsBreathing disturbances (awake)Brain injury secondary to trauma (perinatal or postnatal)A period of regression followed by recovery or stabilisationA period of regression followed by recovery or stabilisation*
Partial/complete loss of acquired spoken languageBruxism (awake)Neurometabolic diseaseAll main criteria and none exclusion criteriaAt least 2 of the 4 main criteria
Gait abnormalities: Impaired (dyspraxic) or absentImpaired sleep patternSevere infection that causes neurological problemsSupportive criteria are not required, although often present in typical RTTAt least 5 out of 11 supportive criteria
Stereotypical hand movements (wringing/squeezing, clapping/tapping, mouthing, washing/rubbing automatisms)Abnormal muscle toneGrossly abnormal psychomotor development in the first 6 months of life
Peripheral vasomotor disturbances
Growth retardation
Small cold hands and feet
Inappropriate laughing/screaming spells
Diminished response to pain
Intense eye communication—‘eye pointing’
  • *Because MECP2 mutations are now identified in some individuals prior to any clear evidence of regression, the diagnosis of ‘possible’ RTT should be given to children under 3 years old who have not lost any skills but otherwise have clinical features suggestive of RTT. These individuals should be reassessed every 6–12 months for evidence of regression. If regression manifests, the diagnosis should then be changed to definite RTT. However, if the child does not show any evidence of regression by 5 years, the diagnosis of RTT should be questioned.