Rett Syndrome

Gene: MECP2

Protein: methyl-CpG-binding protein 2

Clinical Characteristics

Classic Rett Syndrome

  • Typically affects females (males with mosaicism or 47,XXY have been reported)
  • Normal prenatal and newborn history
  • Apparently normal psychomotor development for first 6 to 18 months of life
  • Short developmental plateau followed by regression in language and motor skills
  • Cognitive impairment/mental retardation without further regression
  • Repetitive, stereotypic hand movements with loss of purposeful hand movements
  • Autistic features
  • Acquired microcephaly
  • Seizures
  • Bruxism (teeth grinding)
  • Impaired sleeping pattern
  • Breathing disturbances

Atypical Rett Syndrome

  • Typically affects females
  • Loss or reduction of hand skills, speech, and other communication skills
  • Acquired microcephaly
  • Regression followed by recovery of interaction
  • May or may not have other features of classic Rett syndrome
  • Other presentations with variable courses and different ages of onset

Severe Neonatal Encephalopathy

  • Affects males; rare in females
  • Severe neonatal-onset encephalopathy with microcephaly
  • Abnormal tone and involuntary movements
  • Severe seizures
  • Breathing abnormalities
  • Often die before second year of life

PPM-X Syndrome

  • Females, mild nonprogressive mental retardation
  • Males, severe mental retardation associated with:
    • “PPM” (Psychosis, Pyramidal signs, Macro-orchidism)
    • Parkinsonian features - resting tremor, slowness of movements, and ataxia

MECP2 Duplication Syndrome

  • Affects males; can affect females with an associated translocation or insertion
  • Infantile hypotonia
  • Severe mental retardation
  • Poor speech development
  • Progressive spasticity
  • Recurrent respiratory infections
  • Seizures

Inheritance pattern: X-linked

What Can Be Learned From This Test

Tier 1 testing is performed by sequencing the entire coding region of MECP2. This will detect point mutations, small deletions and small insertions. Reflexive testing for a partial or whole gene deletion by fragment analysis can be carried out; please note on submission form if this tiered approach is being requested.

A negative test result does not rule out a diagnosis of Rett syndrome. Sequencing alone will detect mutations in about 80% of individuals with classic Rett syndrome and in about 40% of individuals with atypical Rett syndrome. Deletion/duplication testing increases the detection rates to about 88% and 43%, respectively.

Sample Requirements

Draw 2ml–4ml of blood in EDTA/purple-top tube (minimum of 1ml–2ml for infants).

Turnaround time: 10-14 business days per tier

CPT Codes and Cost

Tier 1: Full Gene Sequencing 

  • Code: 81302
  • Cost: $685

Tier 2: Dosage

  • Code: 81304
  • Cost: $300

Known Variant Testing

  • Code: 81303
  • Cost: $225

Additional Information