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. 2023 Dec;14(6):493-497.
doi: 10.1159/000530586. Epub 2023 May 12.

Expanding Phenotype of SYT1-Related Neurodevelopmental Disorder: Case Report and Literature Review

Carlo Alberto Cesaroni  1   2 , Carlotta Spagnoli  1 , Margherita Baga  1 , Susanna Rizzi  1 , Daniele Frattini  1 , Stefano Giuseppe Caraffi  3 , Marzia Pollazzon  3 , Livia Garavelli  3 , Carlo Fusco  1
Affiliations

Expanding Phenotype of SYT1-Related Neurodevelopmental Disorder: Case Report and Literature Review

Carlo Alberto Cesaroni et al. Mol Syndromol. 2023 Dec.

Abstract

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 harboring 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 case 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 better delineate the SYT1-related clinical phenotype.

Keywords: Dystonic posture; Epilepsy; Risperidone; SYT1; Valproic acid.

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Conflict of interest statement

The authors have no conflicts of interest to declare.

Figures

Fig. 1.
Fig. 1.
Our patient’s EEG at 21 years of age (20 s/pg, 14 µ/mm, 15 Hz, notch 50 Hz).
Fig. 2.
Fig. 2.
Surgically corrected bilateral calcaneovalgus and metatarsus adductus on the right side (a); dystonic posturing of her hands (b, c).
See this image and copyright information in PMC

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