About the Diagnosis

Rett syndrome (RTT) is most often misdiagnosed as autism, cerebral palsy, or non-specific developmental delay.  There is a simple blood test to confirm the presence of the MECP2 mutation; 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 observed signs and symptoms) 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.

Requirements for Rett syndrome diagnosis

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

Criteria for Rett syndrome diagnosis

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 [Document]

Mutations in another gene on the X-chromosome known as CDKL5 (cyclin-dependent kinase-like 5) can cause an atypical form of Rett syndrome and generally test negative for a MECP2 mutation.  Not everyone with a CDKL5 mutation appears as atypical Rett syndrome.

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

 

Mutations on chromosome 14 on the gene FOXG1 can also be responsible for a congenital variant of Rett syndrome and generally test negative for a MECP2 mutation.  Not everyone with a FOXG1 mutation appears as atypical Rett syndrome.  For more information, visit http://foxg1.com/.

Mutations in another gene on the X-chromosome known as WDR45, which is known to be associated with BPAN syndrome, has recently been found in a few girls who have a clinical diagnosis of Rett syndrome and no positive MECP2 mutation.  For more information about this gene screening, please download this flyer.

 

Testing Centers

DNA Diagnostic Testing Laboratory

Baylor College of Medicine
Houston, TX
P: (713)  798-6555 or (800) 411-4363 (GENE)
Dr. Mike Friez

Greenwood Genetic Center

Greenwood, SC
P: (864) 941-8100 or (888) 442-4363 (GGC-GENE)
Fran Annese, LMSW, CCRC

 

Molecular 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
www.genedx.com
P: (301) 519-2100

Ambry Genetics

15 Argonaut
Aliso Viejo, CA 92656
www.ambrygen.com
P: (866) 262-7943