Rett Syndrome

Author: Fracchia Federico
Date: 13/09/2010


di Fracchia Federico

DEFINITION (Wikipedia)

Rett syndrome is a severe and progressive neurodevelopmental disorder
The disease is congenital, although not immediately apparent, and occurs during the second year of life and within the first four years.Rett syndrome causes severe disability at many levels.

The Diseases DatabaseURL
OMIM single geneURL

The syndrome is named after Andreas Rett, a professor of Austrian origin, who first described it in 1966.

It affects predominantly female subjects.
The incidence of the syndrome has classically been estimated to be 1 / 15000 (U.S.A Epidemiology, 1993). There is also existence of clinical variants that has been demonstrated abnormality of MeCP2, it increases the incidence 1.09/10000. Studies on the prevalence (new cases per year on a given population) reported data ranging between 0.41/10000 2.23/10000 in Switzerland and Sweden (Laurvick CL, 2006).

PubMed: French Epidemiology
PubMed; Australian Epidemiology

After a period of normal development, there is:
1) to stop development and then to a regression or loss of skills acquired.
2) There is a slow development of the skull (of normal size at birth) than the rest of the body between the first 5 and 48 months of life;
3) normal psychomotor development during the first 5 months of life, with subsequent loss of manual skills previously developed and appearance of stereotyped hand movements (twist, hit, bite, squeeze).
4) There is also a progressive loss of interest in the social environment, but sometimes reappears in adolescence.

4 phases of development of Rett syndrome

the main cause of the disease is due to gene MECP2, situated on cromosoma X . It encodes a protein known as MeCP2 or "methyl-CpG binding protein 2". The protein is generally described as transcriptional repressor or as a protein that prevents some specific genes to be expressed. MeCP2 has a portion (domain) capable of binding DNA and another that can turn off the activity of target genes (target genes)


MeCP2 has a region known as MBD or methyl-binding domain capable of binding those DNA sequences after methylation and a region that is responsible instead of silencing genes target, (TRD).MeCP2 has in its final portion of a domain (the C-terminal domain) whose functions are not yet well understood


There are eight points in MECP2 gene sequence (the so-called hot spots) that change with a frequency much higher in other regions of the gene which, when mutated, producing a protein lacking MeCP2 function that can not 'perform its normal functions.


These mutations cause about 63% of alterations of MeCP2.

with the genetic test research of MECP2 gene mutation, the diagnosis can be confirmed more easily.
Molecular diagnosis to determine the RTT is based on DNA sequencing of MECP2, and is made from a simple venipuncture.
To date, however, tested positive 85% of patients diagnosed with Rett syndrome

There is no cure for Rett syndrome. However most of the authors believes that the course of the disease can be modified by a variety of therapies aimed at delaying the progression of motor disability and improve communication skills. For this reason the medication is designed mainly to counter the motor disorder. Were used L dopa and dopamine agonists. These include bromocriptine and lisuride have yielded some positive results.

Improvements in respiratory symptoms and behavioral seizures and were found with the administration of naltrexone, which blocks the production of beta-endorphin inhibition of opioid receptors. To counteract seizures have also successfully used the traditional AEDs (carbamazepine and sodium valproate) or more recent (lamotrigine and gabapentin).

Reversal of Neurological Defects in a Mouse Model of Rett Syndrome

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