Research update – June 2017
The CGF is currently funding four research projects, two of which will finish this year and the principal investigators have all provided progress reports which appear elsewhere in this newsletter. With increasingly limited financial resources, we are considering all proposals very carefully and only fund projects that are of direct benefit to members. However, we do intend to maintain a robust research portfolio and anticipate that funding for this aspect of the charity’s work will increase again over the next few years.
The CGF funding for the project with Dr Kate Tatton-Brown at the Institute of Cancer Research (ICR) is due to finish shortly and this coincides with the publication of a very significant publication by Kate and her colleagues in the Journal of Human Genetics. The CGF started funding the group approximately twelve years ago to help launch the Child Overgrowth (COG) study and there has been a huge research effort over the intervening period, resulting in the identification of several new overgrowth syndromes.
The current funding from the CGF was specifically intended to help ensure that the results of the genetic studies can be transferred rapidly to clinical practice. Kate is ideally placed to do this as she divides her time between genetic research at the ICR and her role as Consultant Geneticist, specialising in growth disorders at St George’s Hospital in London. We have already invited Tatton-Brown-Rahman (TBR) and Weaver families to join the CGF and welcomed several TBR families at the convention last year. We hope that a group of families affected with Weaver Syndrome will join us at the convention this year. It is also the intention of the CGF to support other overgrowth syndromes but some are so rare that it may not be possible to run separate groups for all.
It is very difficult for most parents to understand the details of the genetics and simply knowing that your child has an anomaly with the NSD1 gene is of little practical use. Kate is therefore producing booklets for each syndrome, some of which are already available, that can be given to GPs, schools, health visitors etc to provide basic details of the condition.
There are still many people with unidentified overgrowth syndromes (my daughter Romana is one) and we hope to continue working with Kate over the coming years as more syndromes are identified.
Chloe Lane who is working on the cognitive profile of Sotos Syndrome at the Sheffield University Autism Research Laboratory (ShARL) is also due to finish her project later this year. Previous studies into the behaviour (Chris Oliver) and autistic traits (Joanna Saddington) associated with Sotos syndrome having been carried out but there has never been a large scale study of cognition. Chloe has established that most individuals affected by Sotos syndrome have very similar strengths and weaknesses and that a unique cognitive profile can be identified. This will enable her to produce booklets that can be given to teachers and employers to enable them to understand the difficulties or strengths that an individual is likely to have at school or in the work place.
Chloe has also conducted a study of the autistic traits of Sotos Syndrome and established that many individuals have behaviour that would typically be associated with moderate or severe autism. This work was based on a parental questionnaire and is therefore not a formal diagnosis. I would urge parents to consider seeking a clinical diagnosis if they feel that this would be of benefit to their child. Some clinicians seem to feel that a diagnosis of Sotos Syndrome is sufficient but a dual diagnosis of ASD (autistic spectrum disorder) will often enable teachers to provide more targeted help for the child.
Individuals with Sotos syndrome tend to struggle with certain aspects of maths and during the project, Chloe has undertaken a more specific study on a couple of mathematical aspects of cognition. This was carried out using a smaller group and gave some interesting results which she hopes to include in a publication later this year.
As is so often the case with research projects, Chloe’s work has revealed many areas that could be explored in more detail and she hopes to continue her work on overgrowth disorders after the CGF funding ceases. In particular, she may extend the work to include Weaver, TBRS and other recently identified syndromes.
During the project, Chloe also took the opportunity to investigate autistic traits associated with Russell Silver Syndrome using the same parental questionnaire that was used for Sotos Syndrome. The results were very interesting and showed that some (but by no means all) individuals with RSS have behaviours that would typically be associated with moderate or severe ASD. This clearly warrants further investigation and I am very pleased to say that the trustees recently agreed to award a small grant to ShARL to carry out some further work in this area.
The STAARS project which is led by Professor Karen Temple at Southampton was due to have finished this year but staffing issues have resulted in a slight delay. Dr Kemi Lokulo-Sodipe is planning to return to work within the next few weeks and will then analyse the data that have been collected during the clinical phase of the project. It is possible that the team may wish to include a few more participants so please do consider taking part if you have not already done so. As with all the conditions that we support, one of the first questions that parents with a newly diagnosed child will ask is “what is the prognosis for my child in the long term?” and this project will hopefully help to answer this fundamental question.
The next phase of the SOLID project led by Dr Renuka Dias at Birmingham University has now started and the team are actively recruiting participants. The project will focus on a behavioural assessment (led by Dr Shauna Kearney) but will also involve some MRI imaging to look for anomalies in the brain. The study will be limited to those with confirmed 11p15 hypermethylation, in the first instance, but will hopefully include UPD7 in due course. With limited financial resources, we are very keen to ensure that all research is of direct benefit to members and this is an example of a project that was instigated after discussions between parents and clinicians at CGF conventions.
None of these research projects would have been possible without participants and we are very grateful to all those who volunteered to take part. Please do consider participating in future projects as most research involves statistical analysis and it is much easier to draw robust conclusions with a larger sample size. Please do continue to let us know if you feel that there is a gap in our knowledge of any of the conditions that could be addressed by a research project.
Research Update – December 2017
With several programmes finishing during 2017 our research portfolio is much reduced, and we are now only funding three active projects. This is largely due to our current financial constraints and we hope to be in a position to award further grants in due course (see below).
The project entitled “Neurodevelopmental Outcomes in RSS”, which forms part of the larger SOLID programme, is progressing well and many of you will have heard Dr Renuka Dias talking about the research at the last convention. You will also see an update from Renuka elsewhere in this newsletter.
Dr Megan Freeth and Louisa Robinson at Sheffield University have just started their project entitled “Characteristics of Autistic Spectrum Disorder in RSS” and plan to start testing early in the new year. I appreciate that our RSS members, in particular, have been asked to take part in many research studies in recent years but participants in this study will receive individual feedback which will hopefully be an incentive to take part in this exciting new research.
In 2012, the CGF awarded a grant of £20k to support a project investigating different drug treatments for children affected by thyrotoxicosis. This drug trial, led by Dr Tim Cheetham at the Royal Victoria Infirmary in Newcastle, is still ongoing and we expect to hear the results in another year or two.
At the recent trustees’ meeting we agreed to consider a contribution of £15k to support a project at Manchester University which is investigating the long term medical issues experienced by SGA babies. The grant will enable Dr Reena Perchard to complete a PhD degree under the direction of Professor Peter Clayton and is conditional on the additional funding being obtained from other sources.
The trustees are keen to change the way in which grants are awarded and move to a system in which the CGF asks research groups to submit proposals to address specific issues that have been identified by our members. The exact details of the new scheme have yet to be confirmed but will hopefully have been agreed in time for the next newsletter. However, it is likely that we will announce research awards on an annual or biennial basis and that a budget will be allocated depending on the financial situation of the charity at that time. If the incredible fund-raising effort from CGF members over the last few years can be sustained, we will be able to maintain a valuable research portfolio.
As well as funding research programmes ourselves, we are often asked to make members aware of other relevant projects that have attracted funding from elsewhere. Two current projects in which you may wish to consider participating are an investigation of the cognitive profile, behaviour and autistic traits in Tatton-Brown Rahman and Weaver Syndromes being carried out by Dr Chloe Lane and Dr Megan Freeth at Sheffield University and an investigation of the behavioural aspects and mental health of those with Sotos Syndrome being led by Dr Alice Welham at Birmingham University.
The CGF aims to promote and fund research into the causes and cure of growth and endocrine disorders. The charity may also consider requests for the purchase of equipment or for financial support to deliver conferences or training programmes.
The management committee will nominate one trustee to oversee research funding. Requests for funding will be sent to the nominated trustee who will circulate them to the other members of the management committee unless they clearly do not meet the funding policy.
The nominated trustee will prepare a report on research funding for each management committee meeting. The report will be published in the next issue of the newsletter.
The CGF staff will take responsibility for the administration of the projects and arrange payment of invoices.
The CGF is pleased to consider requests for funding from appropriately qualified medical professionals or university research groups. The CGF may also issue invitations for research proposals on topics that have been identified by trustees or members of the charity.
When unsolicited requests are received, the proposals will be circulated to trustees and a funding decision will be taken on the basis of a simple majority. Discussion of any proposal will normally take place at management meetings but urgent decisions may be taken using email. Where appropriate, the trustees may seek professional advice regarding the merits of research proposals.
When a research topic is identified by the CGF, a statement of requirements will be prepared. The management committee may engage the help of BSPED or other professional organisations to prepare the invitation to bid and to evaluate proposals. The invitation to bid may be announced in the open literature or targeted to a selected group of potential applicants.
Principal investigators will be required to sign research agreements that include the following details
- Starting date and duration of project
- Payment terms
- Reporting procedures (e.g. quarterly progress reports, six monthly meetings, final report)
- Confirmation of ethics approval, if necessary
- Ownership of intellectual property, if appropriate
- Acknowledgement of CGF financial support in all external publications
Research projects will usually be funded from unrestricted funds. However, the CGF will also consider offers of restricted funding from pharmaceutical companies or other organisations to support specific projects. The honorary treasurer must authorise all research funding.
The monitoring procedure will depend on the duration of the project and the financial commitment involved and will be specified in each agreement. As a minimum, principal investigators will be required to submit a short progress report at six monthly intervals but for larger projects, trustees and / or staff may hold review meetings with the principal investigator.
If, as a result of these monitoring procedures, a project is deemed to be making unsatisfactory progress, the principal investigator will be informed in writing. Subsequent invoices will not be paid until agreed research objectives have been met or a satisfactory explanation for the lack of progress has been provided.
As well as submitting regular progress reports as detailed in the research agreement, the principal investigator will also be expected to
- Publish as widely as possible in the open literature (financial support from CGF should be acknowledged in each case)
- Produce an article for the newsletter
- Give a presentation at the convention (if invited)
On completion of research programmes, the outcomes will be evaluated, with the help of professionals if necessary. The projects will be assessed on the basis of the following criteria
- The number of publications in peer reviewed journals, arising directly from the funded project
- Whether the agreed timescales were met and if not, why not
- Whether the research objectives were met in full
- What outcomes were of direct benefit to CGF members
This information will be recorded in a single proforma and retained for at least five years. The proforma will be presented at the next meeting of the Management Committee and a decision will be taken as to whether future proposals would be considered from the same research group.