Genetic syndromes research at ShARL

For Rare Diseases Day 2021 we are publishing a series of blogs about the research on rare genetic syndromes that we do at ShARL. We started our research on rare genetic syndromes in 2014. At this time we realised that although there is a lot of medical and genetic research that improves understanding of rare genetic syndromes, there is far less that aims to improve knowledge and understanding of the impact of syndromes on cognition (how we think and learn) and behaviour. It is really important for families that this type of work is done so that when a diagnosis of a particular syndrome is received, they can be equiped with knowledge about what to expect in terms of development and learn about what educational and environmental support may help children to have optimal life chances and optimal outcomes.

At ShARL we are really passionate about doing work that will help families and we are always keen to hear from families about the types of research they would like to see done. We realise that families often have many unanswered questions and that it can be frustrating when even the specialists don't have clear answers for them, so this is something that we're trying to contribute to improving. To date, we have projects that focus on Sotos syndrome, Tatton-Brown Rahman syndrome, Weaver syndrome, Silver-Russell syndrome, 16p11.2 duplication syndrome, 16p11.2 deletion syndrome, 22q11 deletion syndrome. The projects that we're able to run depend on being able to acquire funding to do so but we're always looking for funding opportunities and organisations to work with to enable projects to run.

In this first blog in our series for Rare Diseases Day 2021 we don't have space to write about all of our work so, instead, I've decided to focus on the syndrome we've published most work on so far. Hopefully this brief overview provides some insight into the types of questions we can answer from our lab doing this type of research. In future we hope to both improve understanding further on the syndromes we have already been working on and to also do research on other syndromes for which there is little current knowledge.

Our research on Sotos syndrome

We began our rare genetic syndromes work on a condition called Sotos syndrome. Much of this work has been funded by the Child Growth Foundation and we
have also recieved support from the Baily Thomas Chaitable Fund. This work was led by Dr Chloe Lane. 

Sotos syndrome is an overgrowth disorder which is present from birth. Individuals with Sotos syndrome tend to have an enlarged head circumferance, characteristic facial features and some degree of intellectual disability. It is caused by haploinsufficiency of the NSD1 gene on chromosome 5. It affects males and females equally and in the majority of cases the NSD1 abnormalities that cause Sotos syndrome are "de novo" meaning that they occur spontaneously and the condition is not inherited.

One of our research projects on Sotos syndrome investigated whether there is a specific learning profile associated with the syndrome, i.e. whether there is a consistent profile of relative strengths and difficulties. We found that while those with Sotos syndrome tend to be of overall lower ability than children of the same age, they tend to have relative strengths with verbal skills (both speaking and understanding) but relative difficulty with non-verbal reasoning skills. They tend to have strengths in visuo-spatial memory, so things like remembering routes traveled and where to find things can be a strength. In a piece of research that specifically focused on the different aspects of language we found that while understanding of sentences and vocabulary tends to be quite good, sometimes this may not be apparent during conversations as the social aspects of language, such as turn-taking, using non-verbal cues such as eye-gaze direction or using language in appropriate contexts can be a challenge. Some of these difficulties are also experienced by individuals on the autistic spectrum. So, in another piece of research we investigated how common it is for individuals with Sotos syndrome to display autistic traits. We found that it is really common for those with Sotos syndrome to display autistic traits, with most expressing traits at the "clinically relevant" level. An area of life that individuals with Sotos syndrome find particularly challenging is managing finance and dealing with numbers in general. So, in another piece of research we decided to investigate whether there were any underlying reasons why this might be. We found that those with Sotos syndrome tend to have good estimation skills (termed the "approximate number system") but they have difficulties with impulse control and this may be impairing their maths skills development. In future, it will be important to investigate how this aspect of development can be best supported in order to help children with Sotos syndrome acquire these important numerical skills.

Although quite a brief whistle-stop tour, I hope this overview provides some insight into the sorts of projects we do at ShARL. We will share outcomes of our future projects as they progress and there will be more information about these projects as part of this blog series. If you would like access to any of the research written about in this blog, please email me (m.freeth@sheffield.ac.uk) and I'll be happy to share it directly. Further information on all of the work that we do at ShARL is available on our website.

Thank you for reading!

Dr Megan Freeth

Senior Lecturer in Psychology

Director of the Sheffield Autism Research Lab