SYNGAP1 and Its Related Epileptic Syndromes

Maria Teresa Garozzo; Daniela Caruso; Flavia Maria Consuelo La Mendola; Alessandra Di Nora; Katia Romano; Roberta Leonardi; Raffaele Falsaperla; Antonio Zanghì; Andrea D. Praticò

doi:10.1055/s-0041-1727144

Journal of Pediatric Neurology, Inhaltsverzeichnis

Journal of Pediatric Neurology 2023; 21(06): 411-416
DOI: 10.1055/s-0041-1727144

Review Article

SYNGAP1 and Its Related Epileptic Syndromes

Maria Teresa Garozzo

¹Unit of Pediatric and Pediatric Emergency, Hospital “Cannizzaro,” Catania, Italy

,

Daniela Caruso

²Pediatrics Postgraduate Residency Program, Department of Clinical and Experimental Medicine, Section of Pediatrics and Child Neuropsychiatry, University of Catania, Catania, Italy

,

Flavia Maria Consuelo La Mendola

³Unit of Pediatrics, Caltanissetta Hospital, Caltanissetta, Italy

,

Alessandra Di Nora

²Pediatrics Postgraduate Residency Program, Department of Clinical and Experimental Medicine, Section of Pediatrics and Child Neuropsychiatry, University of Catania, Catania, Italy

,

Katia Romano

⁴Italian Blind Union, Catania Section, Italy

,

Roberta Leonardi

⁵Unit of Rare Diseases of the Nervous System in Childhood, Department of Clinical and Experimental Medicine, Section of Pediatrics and Child Neuropsychiatry, University of Catania, Catania, Italy

,

Raffaele Falsaperla

⁶Unit of Pediatrics and Pediatric Emergency, University Hospital “Policlinico Rodolico-San Marco,” Catania, Italy

⁷Unit of Neonatal Intensive Care and Neonatology, University Hospital “Policlinico Rodolico-San Marco,” Catania, Italy

,

Antonio Zanghì

⁸Department of Medical and Surgical Sciences and Advanced Technology “G.F. Ingrassia,” University of Catania, Catania, Italy

,

Andrea D. Praticò

⁵Unit of Rare Diseases of the Nervous System in Childhood, Department of Clinical and Experimental Medicine, Section of Pediatrics and Child Neuropsychiatry, University of Catania, Catania, Italy

› Institutsangaben

Abstract

Synaptic Ras GTPase-activating protein 1 (SYNGAP1) is abundantly expressed in the postsynaptic space in brain tissue and has a crucial role in the regulation of the excitatory/inhibitory balance and in brain development. It is estimated that SYNGAP1 loss of function variants have an incidence of 1 to 4/10,000 individuals, mostly occurring de novo, even if few cases of vertical transmission of mosaic mutations have been reported. Loss-of-function mutations within this gene have been related with an epileptic encephalopathy characterized by eyelid myoclonia with absences (EMA) and myoclonic-atonic seizures (MAE) with early onset, commonly resistant to antiepileptic drugs (AED). Epilepsy is often associated with other clinical features, including truncal and/or facial hypotonia and/or ataxia with a wide-based and unsteady gate. Other clinical signs are intellectual disability, developmental delay, and behavioral and speech impairment, in a context of a normal neuroimaging study. In selected cases, dysmorphic features, skeletal abnormalities, and eye involvement are also described. The diagnosis of the disorder is usually established by multigene panel and, in unsolved cases, by exome sequencing. Management of the affected individuals involves different specialists and is mainly symptomatic. No clinical trials about the efficacy of AED in SYNGAP1 encephalopathy have been performed yet and Lamotrigine and valproate are commonly prescribed. In more than half of cases, however, epilepsy is refractory to AED.

Keywords

SYNGAP1 - myoclonia - absences - neurodevelopmental delay - intellectual disability - behavior disorders

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Referenzen

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