Genetics
- De novo mutations in the MECP2 (methyl-CpG-binding protein 2) gene on the X chromosome
- Exclusively found in women (gene mutation is on the X chromosome)
- Affected males die in utero or shortly after birth
- Incidence of 1 ~ 10,000 live female births
- Accounts for 10% of the cases of genetically-caused severe intellectual disability in women
Key clinical manifestations
- Summary: Regression of purposeful hand use and spoken language, with the development of gait abnormalities and hand stereotypies. After the period of regression, a stage of stabilization and potentially even improvement ensues, with some individuals partially regaining skills
Normal development until 6 to 18 months of age and then there is:
- Arrest of brain development
- Deceleration of head growth (deceleration of weight and height follows), resulting in microcephaly
- Developmental regression with a loss of spoken language
- Stereotypic hand movements
- For instance: hand wringing and clapping and finger kneading and rubbing
- Extrapyramidal motor dysfunction
- Gait ataxia and truncal apraxia/ataxia
- Spasticity
Importantly, after the period of regression in hand movements, spoken language, and gait abnormalities, there is a stage of stabilization (and possible improvement) with the potential for regaining certain skills.
- Abnormal behaviors
- Inappropriate laughing or screaming
- "Eye pointing", which is described as "intense eye communication"
- Reduced response to pain
- Epilepsy
- Almost 90% of patients with Rett syndrome will manifest with seizures by adulthood (prevalence increases with age).
- Specific EEG Changes: Generalized slowing, Central, short-duration spikes, Increased epileptic changes during sleep
- Autonomic dysfunction
- Sudden, unexpected death (0.3 percent of patients) is attributed to autonomic dysfunction
- Respiratory dysfunction
- Scoliosis
Diagnostic Criteria for Rett Sydnrome
For complete clinical criteria, see Neul et al., “Rett Syndrome.”
Summary of criteria is:
- Regression of acquired purposeful hand skills and acquired spoken language followed by recovery or stabilization
- Gait abnormalities: ataxia and apraxia.
- Stereotypic hand movements
- "Hand wringing/squeezing, clapping/tapping, mouthing and washing/rubbing automatisms"
Symptoms CANNOT be secondary to another known inherited or acquired cause and grossly abnormal psychomotor development in first 6 months of life is an Exclusion Criteria for Rett Syndrome
Clinical Trials
- See ClinicalTrials.gov for a review of the 25+ clinical trials that have been performed in an attempt to treat Rett Syndrome
References
- Armstrong, D. D. “Review of Rett Syndrome.” Journal of Neuropathology and Experimental Neurology 56, no. 8 (August 1997): 843–49.
- Ehinger, Yann, Valerie Matagne, Laurent Villard, and Jean-Christophe Roux. “Rett Syndrome from Bench to Bedside: Recent Advances.” F1000Research 7 (March 26, 2018): 398. https://doi.org/10.12688/f1000research.14056.1.
- Garofalo, E. A., I. Drury, and G. W. Goldstein. “EEG Abnormalities Aid Diagnosis of Rett Syndrome.” Pediatric Neurology 4, no. 6 (December 1988): 350–53.
- Neul, Jeffrey L., Walter E. Kaufmann, Daniel G. Glaze, John Christodoulou, Angus J. Clarke, Nadia Bahi-Buisson, Helen Leonard, et al. “Rett Syndrome: Revised Diagnostic Criteria and Nomenclature.” Annals of Neurology 68, no. 6 (December 2010): 944–50. https://doi.org/10.1002/ana.22124.