Trinity School of Medicine researchers create an education storybook for families with a rare genetic condition associated with autism
On World Autism Awareness Day Dr Ciara Molloy, a Research Fellow in the Autism and Rare Neurodevelopmental Research Group in Trinity College Dublin, spoke to us about the storybook they developed for families of children with NRXN1 deletions. The storybook was developed to educate children and their families following a diagnosis. NRXN1 deletion is a rare synaptic gene condition and is associated with the development of autism spectrum disorder, along with other conditions such as intellectual disability and speech and language delay.
NRXN1 is important in the brain as it is involved in the communication between brain cells called neurons. As the building blocks of the brain, neurons communicate with each other through their points of contact, known as synapses. Rare variation in synaptic genes can affect the development of neurons and how they communicate with each other, which may have broad effects on how someone thinks or behaves.
Autism spectrum disorder is a neurodevelopmental condition in which both clinical and biological heterogeneity is observed. About 0.5-2% of autistic people also have a synaptic gene condition. The research group, led by Professor Louise Gallagher, study a rare synaptic gene condition associated with the development of autism, known as NRXN1 deletions. Dr Molloy explains the group’s broader research focus:
“Our research group is studying people with NRXN1 deletions to better understand the links between genetics, brain development and clinical outcomes. We hope our research will help to better understand the clinical relevance of having a rare genetic condition such as a NRXN1 deletion. We also hope to develop measures that can help understand which treatments, therapies or supports may be most beneficial for individuals with a synaptic gene condition and/or autism that may be in need of them. This research will be useful for families, clinicians and genetic counsellors.”
Collaboration with King’s College London
This research is being conducted in collaboration with a group at King’s College London. The London group study a different synaptic condition, known as SHANK3 deletion (Phelan McDermid syndrome). Both Both NRXN1 and SHANK3 function at different parts of the synapse and play a role in signal transmission within the brain. The Synaptic Gene Study is focused on understanding similarities and differences between people with these two synaptic gene conditions as well as autistic people that do not have a synaptic gene condition. The researchers use an in-depth multi-modal approach to help comprehensively characterise these two rare genetic conditions. This includes interviews, observational assessments, and questionnaires for clinical characterisation, eye-tracking to measure neurocognition, EEG and MRI to measure different aspects of brain function and structure, and biological samples for genetic testing.
This type of research is unique in its approach, and can help to understand how genetics and the underlying molecular and biological mechanisms in the brain, might relate to neurodevelopmental conditions such as autism. Dr Molloy explained:
“By studying rare synaptic gene conditions, we have pre-defined subgroups to assess genetic and biological links to clinical outcomes, which we hope will help to better understand the heterogeneity within autism. We aim to identify brain and neurocognitive markers of NRXN1 and SHANK3 deletions, which may be useful for assessing what therapies or treatments those with synaptic gene conditions and autism or other neurodevelopmental conditions may benefit from. This study is one of many studies being conducted as part of AIMS-2-TRIALS, which is an EU consortium focused on understanding the biology of autism, and the development of biomarkers and new therapies.”
The creation of an educational storybook
The idea for the storybook arose from the lack of information available to parents and children, as well as the feeling of loneliness or isolation that may happen after a diagnosis of a rare condition. Dr Molloy stressed the importance of education:
“It is extremely important that our research findings and clinically relevant information is communicated to families impacted by rare genetic conditions.”
Having received funding from the Trinity College Dublin Equality Fund, Dr Molloy, Professor Gallagher and Isabel Hernandez, a psychology student, created the educational storybook called ‘Ned and Nelly’s NRXN1 Deletion’. Dr Molloy praised Isabel’s involvement in the project, and described how their research informed the project:
“We created two young characters, Ned and Nelly, and Isabel designed some beautiful illustrations to help make learning about NRXN1 deletions fun and easy for families. We used our knowledge from NRXN1 deletion research and the current information to describe strengths and challenges of the two characters who have NRXN1 deletions to help understand what it means to have a NRXN1 deletion, and learn about neurodiversity through a rare genetic condition. Neurodiversity is a term that is used explain differences in the human brain, and how these differences can relate to things like social skills, learning, attention, mood as well as other brain functions. It is important to understand that we all have different strengths and challenges in life, and people are there to help us if we need help. The storybook is designed with questions to help whoever is reading it to reflect on what their own strengths and challenges are, and who can help with their challenges."
The researchers held an online event to show a draft of the work to the families and to receive feedback. Discussions from this event has led to plans for another storybook about the two characters when they grow up. The group are hopeful that this project may encourage the production of storybooks for other rare genetic conditions.
Impact on science and clinical care
The group’s research has clear impact on both scientific knowledge and patient care, as it sheds light on the relationship between genetic variability and clinical/ behavioural characteristics of rare genetic conditions. Dr Molloy explained:
“We know that individuals with NRXN1 deletions can develop conditions such as autism, intellectual disability and speech and language delay, while others do not. Understanding the potential impact of having a genetic condition is important as it can then be provided to families, as well as genetic counsellors and clinicians.
Rare genetic conditions are a useful way to link underlying biological mechanisms, such as synaptic function within the brain, to associated clinical characteristics of neurodevelopmental conditions such as autism. We hope this may help to develop and test how effective different treatments or therapeutic interventions are for specific subgroups within autism spectrum disorder, with the goal of providing better individualised supports and treatment plans for autistic people and/or people with rare genetic conditions that may need them.”
Dr Molloy highlighted the generosity of the families that participate in their research, investing time and effort to complete the study protocols. Dr Molloy stressed that without them, they could not undertake the research. Therefore, it is vital that families are provided with feedback and are updated regularly regarding research findings so that they can see the results of their contributions to research. Speaking about the patients and their families, Dr Molloy said:
“I hope the creation of our storybook will help families and the public to understand the relevance of our research and promote participation and engagement in the future.”
The Synaptic Gene Study is funded by Innovation Medicines Initiative, while the Storybook ‘‘Ned and Nelly’s NRXN1 Deletion’ is funded by the Trinity Equality Fund.