Makindo Medical Notes

Rett Syndrome 👧🧠: A rare neurodevelopmental disorder caused by mutations in the MECP2 gene on the X chromosome. Development is normal for the first 6–18 months, followed by regression in motor, speech, and cognitive skills, alongside stereotypic hand movements and seizures.

About ℹ️

• Genetics: Sporadic disorder due to a de novo mutation in the MECP2 gene (X chromosome).
• Incidence: ~1 in 8,500 females. Embryonically lethal in most males, but rare male cases occur.
• Primarily affects grey matter development and function in the brain.

Aetiology 🧬

• MECP2 gene mutation: Regulates transcription of multiple genes essential for neuronal growth and synaptic plasticity.

Clinical Features 👩‍⚕️

• Normal early milestones → regression at 6–18 months.
• Motor regression: Loss of purposeful hand skills, ataxia, hypotonia, choreiform movements.
• Cognitive/Language regression: Severe loss of verbal communication, learning disability.
• Behavioural: Autistic-like features, irritability, episodes of screaming.
• Characteristic hand-wringing 👐: Stereotypic midline movements.
• Systemic features: Seizures, arrhythmias (palpitations/syncope), GORD, scoliosis, osteoporosis.

Stages of Rett Syndrome 📊

• Early onset (≤18 months): Hypotonia, feeding difficulties, delayed sitting/crawling, loss of interest in toys.
• Regression (1–4 yrs): Severe language & motor loss, autistic-like withdrawal, stereotypic hand movements, breathing irregularities, irritability.
• Plateau (preschool to school age): Seizures, abnormal breathing (apnoea/hyperventilation), arrhythmias, bruxism, sleep problems. Social interaction may stabilise.
• Late deterioration (childhood → adulthood): Loss of ambulation, scoliosis, spasticity, profound motor decline. Seizures may reduce with age.

Investigations 🔍

• Genetic testing: Confirms MECP2 mutation.
• Neuroimaging (CT/MRI): May show cortical and subcortical changes but mainly used to exclude other causes.

Management 💊🤝

• Supportive therapy: No cure; focus on maximising quality of life.
• Anticonvulsants: Seizure control (e.g., valproate, levetiracetam).
• Multidisciplinary input:
  • Physiotherapy (mobility, scoliosis prevention).
  • Speech therapy (communication aids).
  • Dietetic support for feeding/swallowing difficulties.
• Monitoring: Regular checks for scoliosis, arrhythmias (ECG), bone health, nutritional status.
• Psychosocial support: Family counselling and long-term care planning.

References 📚

• Rett Syndrome – NHS

💡 Exam Pearl

Key clue: A previously healthy girl (6–18 months) who regresses, loses language, and develops stereotypic hand-wringing = think Rett Syndrome. Differentiates from autism (which lacks progressive neurological decline).