Testing and Diagnosis

Rett syndrome is most often misdiagnosed as autism, cerebral palsy, or non-specific developmental delay. In the past, making the correct diagnosis called not only for a long list of diagnostic tests and procedures to rule out other disorders, but it also took from months to years waiting to confirm the diagnosis as new symptoms appeared over time. Today, we have a simple blood test to confirm the diagnosis. However, since we know that the MECP2 mutation is also seen in other disorders, the presence of the MECP2 mutation in itself is not enough for the diagnosis of Rett syndrome. Diagnosis requires either the presence of the mutation (a molecular diagnosis) or fulfillment of the diagnostic criteria (a clinical diagnosis, based on signs and symptoms that you can observe) or both. Below is a list of labs to share with your ordering physician that can do the MECP2 sequencing + deletion analysis, and the list of diagnostic criteria.

Consider diagnosis when postnatal deceleration of head growth observed.
Required for typical or classic RTT Required for atypical or variant RTT
  • A period of regression followed by recovery or stabilization
  • All main criteria and all exclusion criteria
  • Supportive criteria are not required, although often present in typical RTT
  • A period of regression followed by recovery or stabilization
  • At least 2 of the 4 main criteria
  • 5 out of 11 supportive criteria
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 automisms
Exclusion criteria for typical RTT
  • Brain injury secondary to trauma (peri– or postnatally), neurometabolic disease, or severe infection that causes neurological problems
  • Grossly abnormal psychomotor development in first 6 months of life
Supportive criteria for atypical RTT
  • 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


Genetic Testing 

Top 5 Reasons for Genetic Testing  

Mutations in another gene on the X-chromosome known as CDKL5 (cyclin-dependent kinase-like 5) can cause an atypical form of Rett Syndrome called the early-onset seizure variant. These individuals have generally tested negative for a MECP2 mutation. Not everyone with a CDKL5 mutation appears as atypical RTT. Other CDKL5 disorders include Infantile Spasms, West Syndrome, Early Onset Seizures, and Autism. CDKL5 mutation testing is not routinely available through most diagnostic labs. If you think your child should have this testing, you should discuss it further with your pediatrician, neurulogist, or geneticist. For more information visit http://www.cdkl5.com/ 

Testing Centers

  • DNA Diagnostic Testing Laboratory
    Baylor of Medicine
    Houston, TX
    P: (713)  798-6555 or (800) 411-4363 (GENE)
  • Dr. Mike Friez
    Greenwood Genetic Center
    Greenwood, SC
    P: (864) 941-8130 or (888) 442-4363 (GGC-GENE)
  • Iris L. Gonzalez, Ph.D.
    Mulecular Diagnostics Laboratory
    Wilmington, DE
    P: (302) 651-6779/6777
  • Center for Human Genetics
    Boston University School of Medicine
    Boston, MA
    P: (617) 638-7083
  • University of Chicago
    Genetic Services Laboratories
    Chicago, IL
    P: (888) 824-3637 or (888) 824-3637 (UC-GENES)
  • Children’s Hospital Boston
    DNA Diagnostic Laboratory
    Boston, MA
    P: (617) 355-7582
  • GeneDX
    207 Gaithersburg, MD 20877
    P: (301) 519-2100