Journal of Pediatric Neurology
DOI: 10.1055/s-0041-1727259
Review Article

Syntaxin Binding Protein 1 Related Epilepsies

Alessandra Fontana*
1  Pediatrics Postgraduate Residency Program, Department of Clinical and Experimental Medicine, Section of Pediatrics and Child Neuropsychiatry, University of Catania, Catania, Italy
,
Maria Chiara Consentino*
1  Pediatrics Postgraduate Residency Program, Department of Clinical and Experimental Medicine, Section of Pediatrics and Child Neuropsychiatry, University of Catania, Catania, Italy
,
Milena Motta
1  Pediatrics Postgraduate Residency Program, Department of Clinical and Experimental Medicine, Section of Pediatrics and Child Neuropsychiatry, University of Catania, Catania, Italy
,
Giuseppe Costanza
1  Pediatrics Postgraduate Residency Program, Department of Clinical and Experimental Medicine, Section of Pediatrics and Child Neuropsychiatry, University of Catania, Catania, Italy
,
Manuela Lo Bianco
1  Pediatrics Postgraduate Residency Program, Department of Clinical and Experimental Medicine, Section of Pediatrics and Child Neuropsychiatry, University of Catania, Catania, Italy
,
Simona Marino
2  Unit of Pediatrics and Pediatric Emergency, University Hospital “Policlinico Rodolico-San Marco,” Catania, Italy
,
Raffaele Falsaperla
2  Unit of Pediatrics and Pediatric Emergency, University Hospital “Policlinico Rodolico-San Marco,” Catania, Italy
3  Unit of Neonatal Intensive Care and Neonatology, University Hospital “Policlinico Rodolico-San Marco,” Catania, Italy
,
4  Unit 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
› Author Affiliations
Funding None.

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.

* The authors have equally contributed to this article.




Publication History

Received: 24 February 2021

Accepted: 25 February 2021

Publication Date:
13 April 2021 (online)

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