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Children with severe learning disabilities often remain dependent on others for round-the-clock care throughout their lives. It’s not always possible to diagnose the exact cause of a child’s disability, meaning important questions remain unanswered: Why is the child affected? What sort of treatments would suit them best? Are their parents at risk of having more children with the same disability? Researchers are developing new genetic tests, to improve diagnosis and help provide answers.
What's the problem and who does it affect?
Difficulties with diagnosis
Some children have very severe learning disabilities, which mean they will be dependent on others for round-the-clock care for the whole of their lives. They may be unable to speak, for example, or deal with everyday tasks such as getting dressed or feeding themselves.
Sadly, children with severe learning disabilities often suffer from other problems too. Some have seizures, they can have problems coordinating their movements and they sometimes repeat certain movements compulsively, endlessly wringing their hands, for example. The children can also have behavioural problems, such as autism.
The more everyone knows about the exact nature of a child’s learning disability, about what is causing their problems, the easier it is to give them the specialist care they need – the right sort of medication, physiotherapy or help to develop ways in which they can communicate and gain a degree of independence in their daily living.
However, diagnosis is often extremely difficult. A range of genetic tests are available, but choosing the correct one is hard. Testing is complex, time consuming, expensive and burdensome – many children have to have repeated blood tests, along with other investigations, such as MRI scans and lumbar punctures. Even then, results can be unsatisfactory and too many children are going undiagnosed.
What is the project trying to achieve?
What causes severe learning disabilities?
The researchers have been caring for children with severe learning disabilities for over 20 years. Both existing and new patients are taking part in this study, all of whom have an undiagnosed disability.
The researchers are looking for genetic changes that cause the children’s learning disabilities. They are also investigating whether or not the children inherited these changes from their parents (Some genetic changes are inherited, whereas others arise spontaneously). The researchers are using two state-of-the-art techniques, called genome-wide microarray analysis and Next-Generation sequencing.
In most cases, the researchers are using samples of DNA that have already been collected and stored. When these are not available, they are taking blood samples from patients and their parents.
The researchers are using what they learn to write guidelines for doctors on how best to diagnose severe learning disabilities in children. The guidelines will give advice on which genetic test to choose, depending on a child’s individual symptoms, and how to tell families about their child’s diagnosis..
What are the researchers' credentials?
The project leader, Professor Jill Clayton-Smith is a hospital consultant specialising in genetics. She has over 20 years’ experience of caring for people with severe learning disabilities and is recognised as a leader in this area of medicine. Together with other international experts, Professor Clayton-Smith and Dr Simon Ramsden have written guidelines on the diagnosis of Angelman syndrome, a severe type of learning disability.
Dr Simon Ramsden set up a specialised diagnostic service for children with Angelman syndrome in the UK. He has also been central to the development of national, and international, quality assurance systems for laboratories that specialise in diagnostic testing. The project team also includes Dr Jill Urquhart who has developed the microarray analysis facility within the Manchester Biomedical Research Centre.
Over the years, the researchers have already gathered detailed information on a large group of patients who have severe learning disabilities. This is a key resource. They also have access to the costly equipment that is needed for the state-of-the-art genetic tests that are being used in this project.
Who stands to benefit from this research and how?
Improving the diagnosis
The researchers hope to improve the lives of children who have a severe learning disability along with seizures, movement difficulties or behavioural problems. That includes children with certain rare syndromes, such as Angelman, Rett, Pitt-Hopkins and Mowat-Wilson syndromes.
The researchers are aiming to develop new genetic tests, along with guidelines on how to incorporate them into the diagnostic process. They hope their work will mean that more children receive an accurate diagnosis, with a clearer explanation of what is causing their disability.
Surveys have shown that having a diagnosis is very important to families. It improves the quality of genetic counselling that families receive - helping answer parents’ questions about why their child has got a learning disability and whether any children they, or their relatives, might have in the future are at risk. It can also relieve parents’ feelings of guilt.
An accurate diagnosis also makes it easier to ensure that a child receives the best possible care for them. It guides doctors and therapists in their choice of treatments and provides information that empowers patients and carers when they are trying to access support.
Further down the line, the researchers hope their work will help in the development of better treatments.
|Project Leader||Professor J Clayton-Smith MBChB MD FRCP|
|Project Team||Dr Jill Urquhart PhDDr Simon C Ramsden PhD FRCPath|
|Project Location||Department of Genetic Medicine, St Mary's Hospital, Manchester and the University of Manchester|
|Project duration||2.5 years|
|Project start date||01-Jan-11|
|Project end date||31-Mar-14|
|Grant code||SP4555, GN1778|