The Rett Syndrome Gene
Rett syndrome is a genetic disorder with a sex-linked, dominant expression pattern. Over 90% of classic RTT cases are shown to have a mutation in the MeCP2 gene. This gene encodes the methyl CpG binding domain protein.
RTT is only seen in girls, since males carrying the mutated MeCP2 gene do not survive.
Rett Syndrome Diagnosis
Different types of RTT exist, but an essential diagnostic feature of the condition is normal prenatal and post natal development up to 6-18 months of age, followed by a regressive period. During the regressive phase there is severe loss of social skills, manual dexterity and cranial growth. Further progression of the disease includes the development of hyperventilation and seizures.
Genetic analysis of the MeCP2 gene can provide molecular confirmation of the clinical diagnosis.
Rett Syndrome Research – Prospects of Future Therapies for Rett Syndrome
After the discovery of the molecular basis of RTT in the late 1990s, strains of laboratory mice showing a similar disease have been created. These mouse models of RTT are considered a good experimental tool for RTT research. The hope is that this will improve the understanding of the disease and allow advances in Rett syndrome treatment.
Some of the new therapies that researchers are examining include:
Genetic modification – these studies are addressing whether restoring normal MeCP2 function has therapeutic benefits. Some studies using RTT mice have indicated there is potential here, but at present these results are not considered to be achievable in a clinical setting.
Pharmacological treatments - amongst the most debilitating symptoms of RTT are respiratory defects. One of the drug treatments for this aspect of RTT that is being developed is desipramine. This has been shown to increase respiratory function and lengthen life span in MeCP2 mutant mice. As a result of these encouraging findings, clinical trials have been initiated.
Diet – clinical trials have reported that some RTT girls given folate and betaine showed mild improvements in alertness and social interaction.
Alternative therapies – the provision of stimulating yet calming environments are believed to be beneficial to Rett sufferers. In addition, complimentary therapies ranging from pet therapy to acupuncture have been used with RTT patients and can provide some comfort.
The aim of finding a cure for Rett syndrome is an ambitious one. However, our understanding of this devastating disease is expanding rapidly. Many working in the field believe that due to recent breakthroughs in RTT research, we now have the potential to develop improved future therapies for Rett syndrome.
Mouse models of Rett syndrome: from behavioural phenotyping to preclinical evaluation of new therapeutic approaches. L.Ricceri, B.De Filippis, G.Laviola. Behavioural Pharmacology, 2008, Vol 19, P501-517.
Epigenetic mechanisms in neurological diseases: genes, syndromes and therapies. R.Urdinguio, J.Sanchez-Mut, M.Estella. Lancet Neurology, 2009, Vol 8, P1056-72.