New research has revealed another gene for Rett syndrome which could lead to new treatments for the disorder.
A research project by scientists from Australia and Israel has identified a genetic variation that influences the severity of symptoms in Rett syndrome.
The scientists have established a correlation between the severity of clinical symptoms and a common brain-derived neurotrophic factor (BDNF) polymorphism and they say patients with the normal BDNF genetic variant had less severe symptoms, with later onset and frequency of seizures.
Dr Helen Leonard from the Australian Rett Syndrome Study at the Telethon Institute for Child Health Research, says the finding was exciting in that it identifies a potential new target for treatment of the debilitating neurological disorder.
Dr Leonard says previously it was known that there is a wide range in the onset and severity of symptoms in patients with Rett syndrome but it was difficult to give families a firm idea of how the disorder would progress and the new information is potentially helpful in predicting the clinical progression, but importantly, offers 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.
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 carried out the genetic testing and say the new findings have established a correlation between the severity of clinical symptoms and BDNF polymorphism.
Dr Christodoulou says those patients with the normal BDNF genetic variant had less severe symptoms, with later onset and frequency of seizures.
He says they must now establish the nature of the interaction between MECP2 and BDNF and if it is possible to stimulate BDNF within patients with Rett syndrome, there is a chance that the onset of seizures can be delayed and some of the more debilitating aspects of the disorder reduced.
Rett syndrome is a childhood neurodevelopmental disorder which almost always only affects females.
Although Rett syndrome is a genetic disorder less than 1% of recorded cases are inherited or passed from one generation to the next - most cases are sporadic, which means the mutation occurs randomly and is not inherited.
Initially Children with Rett's develop and grow normally but gradually symptoms appear which include a loss of purposeful use of the hands, distinctive hand movements, slowed brain and head growth, gait abnormalities, seizures, and mental retardation.
The way Rett syndrome progresses, including the age it starts and the severity of symptoms, varies from child to child; mental and physical symptoms gradually appear such as a loss of muscle tone and as the syndrome progresses, the child loses purposeful use of their hands and the ability to speak - other early symptoms may include problems crawling or walking and diminished eye contact.
The loss of functional use of the hands is followed by compulsive hand movements such as wringing and washing and this period of regression is sometimes sudden.
Another symptom, apraxia - the inability to perform motor functions - is perhaps the most severely disabling feature of Rett syndrome, interfering with every body movement, including eye gaze and speech and children with Rett syndrome often exhibit autistic-like behaviours in the early stages.
Other symptoms may include toe walking, sleep problems, wide-based gait, teeth grinding and difficulty chewing, slowed growth, seizures, cognitive disabilities, and breathing difficulties while awake such as hyperventilation, apnoea (breath holding), and air swallowing.
Rett syndrome is caused by mutations in the MECP2 gene, which is found on the X chromosome and up to 80% of girls with Rett syndrome have the MECP2 genetic mutation.
The remaining 20 to 30% of cases are suspected to be caused by mutations in other parts of the gene or by genes yet to be identified.
Some children may require special equipment and aids such as braces to arrest scoliosis, splints to modify hand movements, and nutritional programs to help them maintain adequate weight; special academic, social, vocational, and support services may also be required in some cases.
Despite the difficulties with symptoms, most individuals with Rett syndrome continue to live well into middle age and beyond.
The finding is published in the international journal Neurology.