How do healthcare providers diagnose Rett syndrome?

Blood Test

Genetic evaluation of a blood sample can identify whether a child has one of the known mutations that cause Rett syndrome.¹ Even if a child has a mutation of the Methylcytosine-binding protein 2 (MECP2) gene (which also occurs in other conditions), the symptoms of Rett syndrome may not always be present, so healthcare providers also need to evaluate the child's symptoms to confirm a diagnosis.¹

Clinical Symptoms

A child must meet the following five necessary criteria to be diagnosed with classic Rett syndrome:^2,3

Main Diagnostic Criteria

• A pattern of development, regression, then recovery or stabilization
• Partial or complete loss of purposeful hand skills such as grasping with fingers, reaching for things, or touching things on purpose
• Partial or complete loss of spoken language
• Repetitive hand movements, such as wringing the hands, washing, squeezing, clapping, or rubbing
• Gait abnormalities, including walking on toes or with an unsteady, wide-based, stiff-legged gait

A slowing of head growth between 3 months and 4 years of age, leading to acquired microcephaly, is also characteristic of Rett syndrome and calls for a diagnosis to be considered.^3,4

For additional information and a listing of the supportive criteria, visit the International Rett Syndrome Foundation webpage .

Healthcare providers will also consider whether any of the following conditions are present. The presence of any of the symptoms below would rule out a Rett syndrome diagnosis.

Atypical Rett Syndrome

Genetic mutations causing some atypical variants of Rett syndrome have been identified. After a blood test to confirm a child's genetic makeup, a healthcare provider may diagnose the child with atypical Rett syndrome if the child demonstrates development, followed by regression and then recovery or stabilization. In addition, the healthcare provider will confirm at least two of the other four main criteria, and five of the 11 supportive criteria before making a diagnosis.²

Other Possible Diagnoses

Sometimes Rett syndrome is misdiagnosed as regressive autism, cerebral palsy, or nonspecific developmental delays.¹

For some males, the features of Rett syndrome occur with another genetic condition called Klinefelter syndrome, in which a boy has two X chromosomes and one Y chromosome. This means that the boy may have one mutated MECP2 gene and one normal MECP2 gene, reducing the effects of the mutated gene.