Novel insight gained into the rare disorder of Rett syndrome

A genetic variation has been discovered, which may determine the intensity of the symptoms associated with the disorder called Rett syndrome. Rett syndrome is said to be a neurodevelopmental disorder, which usually affects girls. This disorder may be characterized by certain clinical features like deceleration of the rate of head growth, small hands and feet, repetitive hand movements, etc. Symptoms associated with this syndrome may include cognitive impairment and social problems among others.

The detection of this disorder in early childhood may not be as simple, because its symptoms may usually be confused with other disorders like cerebral palsy, autism etc. Seemingly, at present there may be no cure for this rarely affecting disorder.

For the purpose of the study, the investigators analyzed the DNA samples and medical data of more than 100 patients. This data was said to have been withdrawn from the Australian Rett Syndrome Database and an Israeli cohort.

The investigators have further stated that, though it was previously known that mutations in the MECP2 gene causes Rett syndrome, the newly uncovered information has provided an in-depth understanding. The recently unveiled data has ascertained an association between a brain-derived neurotrophic factor polymorphism (BDNF) and the intensity of the experienced symptoms.

Study investigator, Professor John Christodoulou, from the NSW Centre for Rett Syndrome Research, Children’s Hospital, Westmead, Sydney, noted that, “Those patients with the normal BDNF genetic variant had less severe symptoms, with later onset and frequency of seizures. We know that BDNF plays a major role in the development, survival and function of brain cells.

Dr Helen Leonard, who heads the Australian Rett Syndrome Study at the Telethon Institute for Child Health Research, said the finding was exciting in that it identifies a potential new target for treatment of the debilitating neurological disorder.

"We know that there is a wide range in the onset and severity of symptoms in patients with Rett syndrome but it has been difficult to give families a firm idea of how the disorder would progress," Dr Leonard said.

"This information is potentially helpful in predicting the clinical progression, but importantly, gives us another area to explore for potential therapies."

In the study, clinical information and DNA samples were gathered from 125 patients from the Australian Rett Syndrome Database and an Israeli cohort coordinated by Dr Bruria Ben Zeev at the Safra Pediatric Hospital, Sheba Medical Centre, Sackler School of Medicine, Tel Aviv. The genetic testing was undertaken by Professor John Christodoulou, from the NSW Centre for Rett Syndrome Research at the Children's Hospital at Westmead in Sydney and Dr Eva Gak from the Sagol Neuroscience Center at the Sheba Medical Centre.

Professor Christodoulou said while it has been established that Rett syndrome is caused by mutations in the MECP2 gene, these new findings have established a correlation between the severity of clinical symptoms and a common brain-derived neurotrophic factor (BDNF) polymorphism.

"Those patients with the normal BDNF genetic variant had less severe symptoms, with later onset and frequency of seizures," Dr Christodoulou said.

"We know that BDNF plays a major role in the development, survival and function of brain cells. What we now have to establish is the nature of the interaction between MECP2 and BDNF."

"It may be that if we can stimulate BDNF within patients with Rett syndrome, there is a chance that we can delay the onset of seizures and reduce some of the more debilitating aspects of the disorder."

The finding is published in the latest edition of the international journal Neurology.

The research was supported by funding from the National Institutes of Health (USA), the National Health and Medical Research Council (Australia), the International Rett Syndrome Foundation and the Rett Syndrome Australian Research Fund.