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Testing & Diagnosis of Rett Syndrome

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Testing & Diagnosis of Rett Syndrome

All material Copyright© 2008-2010 International Rett Syndrome Foundation
Reprinted with the express permission of International Rett Syndrome Foundation (IRSF) as originally published on their Website.

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.

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, neurologist, or geneticist. For more information visit http://www.cdkl5.com/

Testing Centers

DNA Diagnostic Testing Laboratory
Baylor College of Medicine
Houston, TX
Tel: 713-798-6555 or 1-800-411-4363 (GENE)

Dr. Mike Friez
Greenwood Genetic Center
Greenwood, SC
Tel: 864-941-8130 or 1-888-442-4363 (GGC-GENE)

Iris L. Gonzalez, Ph.D.
Molecular Diagnostics Laboratory
Wilmington, DE
Tel: 302-651-6779/6777

Center for Human Genetics
Boston University School of Medicine
Boston, MA
Tel: 617-638-7083

University of Chicago
Genetic Services Laboratories
Chicago, IL
Tel: 888-824-3637 or 1-888-824-3637 (UC-GENES)

Children’s Hospital Boston
DNA Diagnostic Laboratory
Boston, MA
617-355-7582

GeneDX
207 Gaithersburg, MD 20877
http://www.genedx.com
301-519-2100


Necessary criteria (must be present for the diagnosis)

  1. apparently normal prenatal and perinatal history
  2. psychomotor development largely normal through the first six months or may be delayed from birth
  3. normal head circumference at birth
  4. postnatal deceleration of head growth in the majority of patients
  5. loss of achieved purposeful hand skill between ages six months and 2.5 years
  6. stereotypic hand movements such as hand wringing/squeezing, clapping/tapping, mouthing and washing/rubbing automatisms
  7. emerging social withdrawal, communication dysfunction, loss of learned words, and cognitive impairment
  8. impaired (dyspraxic) or failing locomotion


Supportive criteria (not necessary for the diagnosis, but may also be seen)

  1. awake disturbances of breathing (hyperventilation, breath-holding, forced expulsion of air or saliva, air swallowing)
  2. teeth grinding (bruxism)
  3. impaired sleep pattern from early infancy
  4. abnormal muscle tone successively associated with muscle wasting and dystonia
  5. peripheral vasomotor disturbances (cold, blue hands and feet)
  6. scoliosis/kyphosis progressing through childhood
  7. growth retardation
  8. hypotrophic (small) feet; small, thin hands


Exclusion criteria (rule out the diagnosis)

  1. enlarged organs or other signs of storage disease
  2. retinopathy, optic atrophy, or cataract
  3. evidence of brain damage before or after birth
  4. existence of identifiable metabolic or other progressive neurological disorder
  5. acquired neurological disorder resulting from severe infection or head trauma


Diagnostic Criteria for Atypical RTT

Inclusion Criteria

  1. meet at least three of six main criteria
  2. meet at least five of eleven supportive criteria


Six main criteria (must meet three):

  1. absence or reduction of hand skills
  2. reduction or loss of babble speech
  3. monotonous pattern to hand stereotypies
  4. reduction or loss of communication skills
  5. deceleraton of head growth from first years of life
  6. RTT disease profile: a regression stage followed by a recovery of interaction contrasting with slow neuromotor regression


Eleven supportive criteria (must meet at least five):

  1. breathing irregularities
  2. bloating/air swallowing
  3. teeth grinding, harsh sounding type
  4. abnormal locomotion
  5. scoliosis/kyphosis
  6. lower limb muscle atrophy
  7. cold, purplish feet, usually growth impaired
  8. sleep disturbances including night screaming outbursts
  9. laughing/screaming spells
  10. diminished response to pain
  11. intense eye contact/eye pointing


Types of atypical RTT include:

  1. Congenital Onset RTT: developmental delay is noticed shortly after birth with no early normal development; or severe seizures in early infancy impairing early development.
  2. Late Onset RTT: signs are delayed beyond the typical 18 month onset, in some cases to age 10 years or more.
  3. Preserved Speech RTT: milder features are seen
  4. Male RTT: May be seen in males with Klinefelter (XXY) or somatic mosaicism


Featured Organization: International Rett Syndrome Foundation (IRSF)

The core mission of the International Rett Syndrome Foundation is to fund research for treatments and a cure for Rett syndrome while enhancing the overall quality of life for those living with Rett syndrome by providing information, programs, and services.

Please support our contributing organizations and visit International Rett Syndrome Foundation

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