Diagnosis & Testing

Rett syndrome is a clinical diagnosis involving the evaluation of specific clinical symptoms, such as developmental delays and specific behavioral signs. Genetic testing can then confirm variants in the MECP2 gene and support the diagnosis.

Rett Syndrome Diagnosis

Diagnosing Rett syndrome (RTT) is based on clinical observation of symptoms. This includes a period of developmental regression typically emerging between 6 to 18 months of age which guides clinicians toward further evaluation. Due to the complexity of the disorder, a thorough assessment of developmental history, physical signs, and behavioral symptoms is essential.

Unfortunately, individuals often receive incorrect or delayed diagnoses because in its early stages, RTT shares many clinical symptoms with other, more common neurological and developmental disorders like autism, cerebral palsy, and epilepsy. Genetic testing plays a crucial role in supporting the RTT diagnosis by identifying mutations in the MECP2 gene.

What are the criteria for a Rett diagnosis?

Diagnosing Rett syndrome, also known as Typical or Classic RTT, involves assessing a combination of core symptoms, such as slowed growth, loss of motor skills, and impaired communication, which typically appear between six and 18 months of age.

Required for Typical or Classic RTT

Main Criteria

Partial or complete loss of acquired purposeful hand skills.
Partial or complete loss of acquired spoken language
Gait abnormalities: Impaired (dyspraxic) or absence of ability.
Stereotypic hand movements such as hand wringing/squeezing, clapping/tapping, mouthing and washing/rubbing automatisms

Exclusion Criteria

Supportive Criteria

Breathing disturbances when awake
Bruxism when awake
Impaired sleep pattern
Abnormal muscle tone
Peripheral vasomotor disturbances
Scoliosis/kyphosis
Growth retardation
Small cold hands and feet
Inappropriate laughing/screaming spells
Diminished response to pain
Intense eye communication - “eye pointing”

Atypical or Variant RTT

Atypical Rett syndrome shares the progressive nature of classic Rett but can vary widely based on the genetic mutation and severity of symptoms. While both classic and atypical Rett syndromes share similar symptoms, including developmental regression, loss of motor skills, and impaired communication, atypical Rett syndrome is often milder and has a later onset, less severe symptoms, or a different progression.

Why genetics testing?

Genetic testing plays a critical role in supporting a clinical diagnosis of Rett syndrome by identifying the specific mutation present in the MECP2 gene. This testing not only provides diagnostic certainty but also helps families understand the specific mutation affecting their child, enabling access to targeted resources and care options.

Confirm clinical diagnosis

Provide information about the specific mutation

Impact eligibility for clinic trials and natural history studies

Contribute to growing knowledge of MECP2

In very rare circumstances, inform recurrence risk in future pregnancies

Newborn Screening

The availability and development of powerful new technologies of genetic testing have led to increased interest in their use to screen newborns for genetic disorders, like RTT, before symptoms appear. It’s important to understand that while current genetic tests can identify variants in the MECP2 gene, having a variant does not always mean a child will develop Rett syndrome.

At this time, as there are no approved treatments for asymptomatic infants, newborn screening for Rett syndrome is of limited, if any, direct benefit, and may cause unnecessary stress for parents. For families with concerns, it’s best to consult with a knowledgeable healthcare provider who can explain the benefits and limitations of testing, address your questions, and provide tailored advice.