Journal of Pediatric Neurology
DOI: 10.1055/s-0041-1727139
Review Article

The Spectrum of DEPDC5-Related Epilepsy

Giulia Salomone
1  Pediatrics Postgraduate Residency Program, Section of Pediatrics and Child Neuropsychiatry, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
,
Mattia Comella
1  Pediatrics Postgraduate Residency Program, Section of Pediatrics and Child Neuropsychiatry, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
,
Anna Portale
2  Unit of Pediatrics, Avola Hospital, Siracusa, Italy
,
Giulia Pecora
1  Pediatrics Postgraduate Residency Program, Section of Pediatrics and Child Neuropsychiatry, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
,
Giuseppe Costanza
1  Pediatrics Postgraduate Residency Program, Section of Pediatrics and Child Neuropsychiatry, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
,
Manuela Lo Bianco
1  Pediatrics Postgraduate Residency Program, Section of Pediatrics and Child Neuropsychiatry, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
,
Sarah Sciuto
1  Pediatrics Postgraduate Residency Program, Section of Pediatrics and Child Neuropsychiatry, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
,
Elena R. Praticò
3  Unit of Pediatrics, Carpi Hospital, Carpi, Italy
,
Raffaele Falsaperla
4  Unit of Pediatrics and Pediatric Emergency, University Hospital “Policlinico Rodolico-San Marco,” Catania, Italy
5  Units of Neonatal Intensive Care and Neonatology, University Hospital “Policlinico Rodolico-San Marco,” Catania, Italy
› Author Affiliations

Abstract

Disheveled EGL-10 and pleckstrin domain-containing protein 5 (DEPDC5) is a key member of the GAP activity toward rags complex 1 complex, which inhibits the mammalian target of rapamycin complex 1 (mTORC1) pathway. DEPDC5 loss-of-function mutations lead to an aberrant activation of the mTOR signaling. At neuronal level, the increased mTOR cascade causes the generation of epileptogenic dysplastic neuronal circuits and it is often associated with malformation of cortical development. The DEPDC5 phenotypic spectrum ranges from sporadic early-onset epilepsies with poor neurodevelopmental outcomes to familial focal epilepsies and sudden unexpected death in epilepsy; a high rate of inter- and intrafamilial variability has been reported. To date, clear genotype–phenotype correlations have not been proven. More studies are required to elucidate the significance of likely pathogenic/variants of uncertain significance. The pursuit of a molecular targeted antiepileptic therapy is a future challenge.



Publication History

Received: 01 September 2020

Accepted: 24 February 2021

Publication Date:
13 April 2021 (online)

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