Syntaxin Binding Protein 1 Related Epilepsies

Alessandra Fontana; Maria Chiara Consentino; Milena Motta; Giuseppe Costanza; Manuela Lo Bianco; Simona Marino; Raffaele Falsaperla; Andrea D. Praticò

doi:10.1055/s-0041-1727259

Journal of Pediatric Neurology, Inhaltsverzeichnis

Journal of Pediatric Neurology 2023; 21(04): 256-263
DOI: 10.1055/s-0041-1727259

Review Article

Syntaxin Binding Protein 1 Related Epilepsies

Alessandra Fontana‡^*

¹Pediatrics Postgraduate Residency Program, Department of Clinical and Experimental Medicine, Section of Pediatrics and Child Neuropsychiatry, University of Catania, Catania, Italy

,

Maria Chiara Consentino‡^*

¹Pediatrics Postgraduate Residency Program, Department of Clinical and Experimental Medicine, Section of Pediatrics and Child Neuropsychiatry, University of Catania, Catania, Italy

,

Milena Motta

¹Pediatrics Postgraduate Residency Program, Department of Clinical and Experimental Medicine, Section of Pediatrics and Child Neuropsychiatry, University of Catania, Catania, Italy

,

Giuseppe Costanza

¹Pediatrics Postgraduate Residency Program, Department of Clinical and Experimental Medicine, Section of Pediatrics and Child Neuropsychiatry, University of Catania, Catania, Italy

,

Manuela Lo Bianco

¹Pediatrics Postgraduate Residency Program, Department of Clinical and Experimental Medicine, Section of Pediatrics and Child Neuropsychiatry, University of Catania, Catania, Italy

,

Simona Marino

²Unit of Pediatrics and Pediatric Emergency, University Hospital “Policlinico Rodolico-San Marco,” Catania, Italy

,

Raffaele Falsaperla

²Unit of Pediatrics and Pediatric Emergency, University Hospital “Policlinico Rodolico-San Marco,” Catania, Italy

³Unit of Neonatal Intensive Care and Neonatology, University Hospital “Policlinico Rodolico-San Marco,” Catania, Italy

,

Andrea D. Praticò

⁴Unit 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

Syntaxin binding protein 1 (STXBP1), commonly known as MUNC18–1, is a member of SEC1 family membrane trafficking proteins; their function consists in controlling the soluble N-ethylmaleimide-sensitive factor attachment protein receptors complex assembly, making them essentials regulators of vesicle fusion. The precise function and molecular mechanism through which Munc18–1 contributes to neurotransmitter releasing is not entirely understood, but several evidences suggest its probable role in exocytosis. In 2008, heterozygous de novo mutations in neuronal protein Munc18–1 were first referred as a cause of Ohtahara syndrome development. Currently, a wide examination of the published data proved that 3.1% of patients with severe epilepsy carry a pathogenic de novo mutation including STXBP1 and approximately 10.2% of early onset epileptic encephalopathy is due to an aberrant STXBP1 form codified by the mutated gene. STXBP1 mutations can be associated to a wide clinical heterogeneity. All affected individuals show developmental delay and approximately the 95% of cases have seizures and early onset epileptic encephalopathy, characterized by infantile spasms as the main consistent feature. Burst suppression pattern and hypsarrhythmia are the most frequent EEG anomalies. Other neuronal disorders include Rett syndrome and behavioral and movement disorders. Mild dysmorphic features have been detected in a small number of cases. No genotype–phenotype correlation has been reported. Management of STXBP1 encephalopathy requires a multidisciplinary approach, including epilepsy control and neurological rehabilitation. About 25% of patients are refractory to standard therapy. A single or combined antiepileptic drugs may be required. Several studies described vigabatrin, valproic acid, levetiracetam, topiramate, clobazam, and oxcarbazepine as effective in seizure control. Lamotrigine, zonisamide, and phenobarbital are also commonly used. To date, it remains unclear which therapy is the most effective. Severe morbidity and high mortality are inevitable consequences in some of these patients.

Keywords

STXBP1 - syntaxin - genetics - encephalopathy - epilepsy

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Referenzen

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