Supplementary Material for: Expanding phenotype of SYT-1 related neurodevelopmental disorder: case report and literature review

Introduction: Synaptotagmin-1 (SYT1), the predominant SYT isoform in the central nervous system, likely acts by promoting vesicle docking, deforming the plasma membrane via Ca2+-dependent membrane penetration. Case presentation: Here we describe a 21-year-old woman harbouring a novel variant in the SYT1 gene, who presents with a complex phenotype featuring severe intellectual disability, absent speech, behavioral abnormalities, motor stereotypies, dystonic posturing of her hands, a hyperkinetic movement disorder in her childhood, infantile hypotonia, sialorrhea, mild dysmorphic features, epilepsy, peculiar EEG findings, and severe scoliosis. Discussion: Based on our cases and literature review on the 22 previously described patients, we can confirm a complex neurodevelopmental disorder in which, unlike other synaptopathies, epilepsy is present in a subset of cases (including our patient: 5/23, 22%), although characteristic EEG changes are far more common (10/23, 43.5%). Our patient's age allows us to provide long-term follow-up data and thus to better delineate the SYT1-related clinical phenotype.