The SynGAP Research Fund 501(c) today announced a grant to Dr. Danielle Andrade, Dr. Miles Thompson, Dr. Ryan Yuen, Dr. Rogier Kerssebook, and Dr. Anatoljevna Anna Kattentidt to support research on SynGAP-Related Disorder (SRD) in adults. SRD is a rare neurodevelopmental disorder that causes severe intractable epilepsy, and intellectual disability, and is one of the leading genetic causes of autism.
Dr. Andrade's team recently published the only research on SRD in adults in Neurology Genetics, Rong 2023 which SRF was instrumental in encouraging and supporting via recruitment. See Dr. Andrade's readout on this work at the 2022 SRF SYNGAP1 Conference here. The grant SRF is announcing today will build on that groundbreaking work.
Dr. Andrade, MD, the principal investigator for this work says "This research holds deep significance not just for the adults in this study but also for children affected by SYNGAP1. As children become adults, investigating the outcomes of SYNGAP1 is pivotal in empowering families and clinicians alike, equipping them to screen for, diagnose, and manage manifestations seen in adults. Also, findings of this study will be important to guide precision therapies as well as evaluate their efficacy."
Michael Graglia, Managing Director of SRF, and father to a child with SRD says "Dr. Andrade is the world's leading expert in adults with DEEs, the SYNGAP1 community is very fortunate to have her attention focused on our disease. She and her colleagues are world-class."
Dr. Marta Dahiya, MD, SRF's Head of Clinical and mother to an adult with SRD says, "While many patients today are not yet adults, they will all become adults and this research will inform and support their care and created the opportunity for adult patients to be included in therapeutic studies. Every family should be thrilled about this work."
It is exciting to see this transatlantic cooperation where the large number of adults with SYNGAP1 Related Disorders in the Netherlands are able to be studied and included in this essential work."
Katrien Deckers, head of SRF-Europe
How to sign up
Families with a loved one with SYNGAP1 Related Disorder age 16 or older can join the accessible online study by emailing [email protected], more information is available in the study flyer.
About the project
The primary goal is to comprehensively understand the adult phenotypes and natural history of SRD patients, as well as the differences between those with and without epilepsy, in order to promote optimal care among adult patients.
They will investigate the presence of seizures and their severity, movement abnormalities, adaptive skills, behavior, gastrointestinal symptoms, sleep difficulties, and comorbidities among patients at our Adult Genetic Epilepsy (AGE) clinic in Canada, at the adult SYNGAP1 clinic in the Netherlands and externally through patient organizations such as the SynGAP Research Fund.
They will also determine the genotype/phenotype correlations between SYNGAP1 patients with and without epilepsy. This will be achieved via WGS sequencing to search for rare variants with large effect size that influences the phenotype, and the contribution of common variants to individual features of the phenotype, through calculating the polygenic risk score (PRS) for different comorbidities. This research will provide valuable insight into the unique experiences and clinical outcomes of adult patients with SRF while promoting dialogue on the importance of precise and timely diagnosis and treatment of adult patients.
About the team
Dr. Danielle Andrade, MD, MSc, FRCPC, is the Medical Director of the Epilepsy Program at University Health Network and founder and Director of Krembil Neuroscience Institute Adult Genetic Epilepsy (AGE) Program. Dr. Miles Thompson, Ph.D., GCGCVI Scientific Associate, is with Krembil Research Institute, Toronto Western Hospital, and University Health Network. Dr. Ryan Yuen, Ph.D. is the Senior Scientist, Genetics & Genome Biology Program, at The Hospital for Sick Children - Toronto, Canada. Dr. Rogier Kerssebook, MD, Ph.D. is a Consultant in Clinical Genetics, at Erasmus Medical Centre, Rotterdam, The Netherlands. Dr. Anatoljevna Anna Kattentidt, MD, is a Clinical Geneticist and Physician, at Erasmus Medical Center, Rotterdam, The Netherlands.
University Health Network, Toronto, Canada - https://www.uhn.ca
The Hospital for Sick Children, Toronto, Canada - https://www.sickkids.ca
Erasmus Medical Centre, Rotterdam, the Netherlands - https://www.erasmusmc.nl/nl-nl/
About SYNGAP1-related intellectual disability (SRD)
SYNGAP1-related intellectual disability (US ICD-10 F78.A1 / Global ICD-11 LD90.Y) is a rare genetic disorder caused by variants on the SYNGAP1 gene that reduce SynGAP protein levels. This protein acts as a regulator in the synapses (where neurons communicate with each other). When SynGAP protein levels are too low, we see an increase in excitability in the synapses making it difficult for neurons to communicate effectively. This leads to many neurological issues seen in SynGAP patients.
Symptoms of SYNGAP1 include intellectual disability; epilepsy; hypotonia (low muscle tone); gross and fine motor skill delays; autism spectrum disorder; gastro-intestinal issues; sleep and behavior disorders and visual abnormalities.
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