Another gene found for Rett syndrome

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Another gene found for Rett syndrome

Published: Wednesday, 22-Apr-2009

Medical Condition News

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 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.