Rett syndrome (RS)

Rett syndrome is a sporadic pervasive developmental disorder which is observed almost exclusively in females. (1,2)

The prognosis is poor, with symptomatic relief being the only treatment option.

Rett syndrome (RS) is a neurodevelopmental syndrome affecting almost exclusively female children and first appearing at 7–18 months

• prior to the onset of symptoms, development appears normal
• after symptomatic onset patient development deteriorates rapidly and severe dementia, autism and other features develop
• the locus for inheritance of this condition is Xq28
  • RS results from mutations in the in the methyl-CpG-binding protein-2 gene (MECP2)
  • inherited as an X-linked dominant
  • most cases are sporadic; de novo mutations occur almost exclusively on the paternally derived X chromosome
  • prevalence 1 in 10,000 to 1 in 15,000 female births
• is not a neurodegenerative condition, rather it is a progressive disorder involving multisystem symptom evolution over time
• 70% of patients with RS live to at least 50 years of age
  
  
• features associated with RS include:
  • short stature
  • cachexia
  • head circumference is normal at birth but there is deceleration of head growth
    • growth of the head decelerates between six months and four years and consequent microcephaly
  • bruxism of the teeth
  • cardiological features include prolonged QTc interval and T-wave abnormalities
  • respiratory features include
    • periodic apnoea whilst awake
    • breath holding
    • intermittent hyperventilation
  • abdominal features include
    • constipation
    • gastroesophageal reflux
  • skeletal abnormalities include scoliosis; kyphosis
  • patients have small and cold feet
  • neurological features
    • development is normal until until 6-18 months
    • subsequent development of mental retardation, spasticity
    • seizures develop in up to 75%
  • behavioural/psychiatric manifestations include
    • autistic behaviours
    • hand stereotypies - often clasped together, with wringing movements and clapping
    • sleep disturbance
    • bruxism
    • breath holding

Notes:

* there have been rare reports of Rett syndrome in males

Reference

1. Asuncion R et al. Rett Syndrome. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Mar.
2. Fu C et al. Consensus guidelines on managing Rett syndrome across the lifespan. BMJ Paediatr Open. 2020 Sep 13;4(1):e000717.