Rett Syndrome Notes for MD and DM level

Rett Syndrome

Definition

Rett syndrome is a neurodevelopmental disorder that primarily affects girls, characterized by normal early development followed by regression of acquired skills, especially speech and purposeful hand movements, with onset typically between 6–18 months of age.

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Etiology

• Genetic cause: Mutation in MECP2 gene (methyl-CpG-binding protein 2) on the X chromosome (Xq28)

• Inheritance: Usually sporadic (de novo); rarely familial

• Pathophysiology: Dysfunction of MECP2 protein → abnormal brain maturation and synaptic development

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Epidemiology

• Affects 1 in 10,000–15,000 female births

• Lethal in males (most do not survive infancy unless mosaic or XXY)

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Clinical Features

Phases of Disease

1. Early Onset (6–18 months)

   • Normal development initially

   • Gradual loss of interest in surroundings

   • Loss of purposeful hand skills

   • Deceleration of head growth (acquired microcephaly)

2. Rapid Destructive Phase (1–4 years)

   • Loss of speech and purposeful hand use

   • Stereotyped hand movements: hand-wringing, washing, clapping, or mouthing

   • Gait ataxia, truncal apraxia

   • Autistic-like behavior

3. Plateau Phase (2–10 years)

   • Some improvement in social interaction and eye contact

   • Persistent motor problems and seizures

4. Late Motor Deterioration (>10 years)

   • Progressive scoliosis, muscle wasting, rigidity, dystonia

   • Loss of ambulation in many cases

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Other Features

• Breathing abnormalities: hyperventilation, apnea during wakefulness

• Seizures: common (up to 90%)

• Bruxism, cold/purple extremities (autonomic dysfunction)

• Sleep disturbances

• Growth retardation

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Investigations

• Genetic testing: MECP2 mutation analysis (diagnostic)

• EEG: slowing with epileptiform activity

• MRI brain: may show nonspecific atrophy

• Metabolic tests: normal (to rule out other causes)

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Diagnosis

• Clinical + confirmed MECP2 mutation

• Diagnostic criteria include:

  • Regression after normal early development

  • Loss of purposeful hand skills and spoken language

  • Gait abnormalities

  • Stereotypic hand movements

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Differential Diagnosis

• Autism spectrum disorder

• Angelman syndrome

• Cerebral palsy (especially ataxic type)

• Childhood disintegrative disorder

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Management

• No cure – supportive and multidisciplinary care

  • Physiotherapy & occupational therapy: maintain mobility

  • Speech therapy: communication support (eye-tracking devices)

  • Antiepileptics: for seizures

  • Nutritional support: adequate calories, manage feeding difficulties

  • Behavioral therapy: improve interaction

  • Orthopedic care: for scoliosis, contractures

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Prognosis

• Progressive but non-degenerative

• Life expectancy: many survive into adulthood (40–50 years)

• Main causes of death: sudden unexplained death, pneumonia, cardiac arrhythmias

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Mnemonic (Key features) — “RETT”

• R = Regression (speech, hand skills)

• E = Episodic breathing abnormalities

• T = Typical hand movements (wringing, washing)

• T = Tiny head (acquired microcephaly)