Rett syndrome (RS)

Last reviewed 01/2018

Rett syndrome is a sporadic pervasive developmental disorder which is observed almost exclusively in females (see notes at end of page)

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

Rett syndrome (RS) is a neurodevelopmental syndrome affecting almost exclusively female children of 17-18 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
  • features associated with RS include:
    • short stature
    • cachexia
    • head circumference is normal at birth but thereis 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%
    • behavioral/psychiatric manifestations include
      • autistic behaviors
      • hand stereotypies - often clasped together, with wringing movements and clapping
      • sleep disturbance
      • bruxism
      • breath holding


* there have been rare reports of Rett syndrome in males

  • four male patients in the same family have Rett syndrome with severe mental retardation (3)
  • two males in a second family had progressive spasticity (4)


  1. Ausio J et al. Syndromes of Chromatin remodeling. Clinical Genetics 2003; 64(2):83-95
  2. Percy A et al "Rett syndrome and the autistic disorders". Neurol. Clin. 1990, 8(3), p.659-76
  3. Orrico A, Lam C, Galli L et al. MECP2 mutation in male patients with non-specific X-linked mental retardation . FEBS Lett 2000: 481 (3): 285 288.
  4. Meloni I, Bruttini M, Longo I et al. A mutation in the Rett syndrome gene, MECP2, causes X-linked mental retardation and progressive spasticity in males . Am J Hum Genet 2000: 67: 982 985.