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Journal of Pediatric Neurology 2023; 21(04): 273-282
DOI: 10.1055/s-0041-1727258
Review Article

DNM1 Gene and Its Related Epileptic Phenotypes

Milena Motta
1   Pediatrics Postgraduate Residency Program, Section of Pediatrics and Child Neuropsychiatry, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
,
Maria Chiara Consentino
1   Pediatrics Postgraduate Residency Program, Section of Pediatrics and Child Neuropsychiatry, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
,
Alessandra Fontana
1   Pediatrics Postgraduate Residency Program, Section of Pediatrics and Child Neuropsychiatry, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
,
Laura Sciuto
1   Pediatrics Postgraduate Residency Program, Section of Pediatrics and Child Neuropsychiatry, Department of Clinical and Experimental Medicine, University of Catania, 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
,
Elena R. Praticò
4   Carpi Hospital, Carpi, Italy
,
Stefania Salafia
5   Lentini Hospital, Lentini, Italy
,
Antonio Zanghì
6   Department of Medical and Surgical Sciences and Advanced Technology “G.F. Ingrassia,” University of Catania, Catania, Italy
,
Andrea D. Praticò 
7   Department of Clinical and Experimental Medicine, Unit of Rare Diseases of the Nervous System in Childhood, Section of Pediatrics and Child Neuropsychiatry, University of Catania, Catania, Italy
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Abstract

The phenotypic variety associated to mutations in dynamin 1 (DNM1), codifying the presynaptic protein DNM1 has been increasingly reported, mainly related to encephalopathy with intractable epilepsy; currently, it is known the phenotype related to DNM1 gene mutations is relatively homogeneous with developmental delay, hypotonia, and epilepsy characterized by infantile spasms and possible progression to Lennox-Gastaut syndrome. By examining all the papers published until 2020 (18 articles), we compared data from 30 patients (extrapolated from 5 papers) with DNM1 mutations, identifying 26 patients with de novo mutations in DNM1. Nine patients (33.3%) reported the recurrent mutation p.Arg237Trp. A usual phenotype observed comprises severe to deep developmental delay and muscular hypotonia in all patients with epilepsy beginning with infantile spasms, which often evolved into Lennox-Gastaut syndrome. Data about GTPase or central domains mutations, and existing structural modeling and functional suggest a dominant negative effect on DMN1 function. Generally genetic epilepsies consist of a wide spectrum of clinical features, unlike that, DNM1-related CNS impairment phenotype is quite uniform. In up to one third of patients it has been found variant p.Arg237Trp, which is one of the most frequent variant detected in epileptic encephalopathies. The understanding of DNM1 function opens up the chance that this gene would become a new therapeutic target for epilepsies.

Keywords

dynamin 1 - synaptic - vesicle - epilepsy - intellectual disability


Publication History

Received: 23 February 2021

Accepted: 25 February 2021

Article published online:
21 May 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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