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