Authors :
Ilakkiah Chandran, PhD (c) – University of Toronto, University Health Network
Presenting Author: Quratulain Zulfiqar Ali, MD, MSc (c) – University of Toronto, University Health Network
Marlene Rong, MSc, MD (c) – University of Toronto, University Health Network
Katrien Deckers, Masters in Finance – SynGAP Research Fund EU
Marta Dahiya, MD – SynGAP Research Fund
Encarnacion Postigo Pinazo, PhD – University of Malaga
Silvia De Vincentils, MD – University of São Paulo (FMUSP
Giovanna Rulo, MD – University of São Paulo (FMUSP)
Merel Van T. Hoff, MSc – Zuidwester, Middelharnis
J Michael Graglia, BS – Syngap Research Fund
Aaron Harding, MSc, CLS, MLS(ASCP)SBB – SynGAP Research Fund
Lauren Perry, Rare Disease Advocate – SynGAP Research Fund
Corey Baysden, DMSC – SynGAP Research Fund
Carlos Caparros, MD – SynGAP Research Fund
Victoria Arteaga, MBA – SynGAP Research Fund
Andreas Jimenez-Gomez, MD – Baylor College of Medicine
Eduard Bercovici, MD – Southern Ontario Epilepsy Clinic
Paula Texeira Marques, MD – McMaster University
Kette Valente, MD – University of São Paulo (FMUSP)
Anja Katttentidt, MD – Zuidwester, Middelharnis
Rogier Kerseeboom, MD – Zuidwester, Middelharnis
Danielle Andrade, MD, MSc, FRCPC – Institute of Medical Science, University of Toronto
Rationale:
SYNGAP1-DEEs are associated with neurological, psychiatric and autonomic dysfunction. While pediatric cases are well described, adult outcomes remain poorly characterized. This study aims to investigate the adult SYNGAP1-DEE phenotype and evaluate how patients’ clinical manifestations evolve over time. Methods:
caregiver-reported outcomes assessing seizures, adaptive skills, sleep, pain responsiveness, communication, gastrointestinal symptoms, and caregiver burden.
Results:
70 individuals with pathogenic or likely pathogenic SYNGAP1 variants were recruited. Preliminary analysis of 30 participants (median age 21 years; range 16–68) revealed that 63% experienced at least one seizure type in the past year. Seizure types occurring weekly or more frequently included non-convulsive (37%), convulsive (10%), isolated epileptic spasms (7%), and epileptic spasms with jerks (10%).
Other findings included:
< ![if !supportLists] >· < ![endif] >Moderate to severe intellectual disability in 93%
< ![if !supportLists] >· < ![endif] >Moderate to severe reciprocal social behaviors that hindered daily social interactions in 70%
< ![if !supportLists] >· < ![endif] >Reduced responsiveness to pain in 83%
< ![if !supportLists] >· < ![endif] >77% of participants could walk independently or with minimal assistance
< ![if !supportLists] >· < ![endif] >67% of participants presented with ataxia.
< ![if !supportLists] >· < ![endif] >Regression of motor abilities was present in 23%.
< ![if !supportLists] >· < ![endif] >Although 60% reportedly sleep more than 8 hours nightly, 33% exhibit symptoms of sleep disorders.
< ![if !supportLists] >· < ![endif] >90% of participants consumed standard meals, however, 50% experienced moderate to severe constipation.
< ![if !supportLists] >· < ![endif] >53% were using a diaper or timed toileting.
Caregiver-reported patient quality of life exceeded 70 on a scale from 0 to 100 in 63% of cases. Caregivers themselves reported high fulfillment (93%), yet also, substantial burden, including relational difficulties (47%), mental health challenges (83%), physical health issues (60%), and financial strain (40%).
Conclusions:
Preliminary findings highlight the clinical phenotype and caregiving burden associated with SYNGAP1-DEEs in adulthood. Phenotype and genotype correlations will provide deeper insight into the genetic contributions to these outcomes, and further analyses of the full cohort are expected to clarify the long-term clinical course of SYNGAP1-DEE.
Funding: SynGAP Research Fund