The Spectrum of DEPDC5-Related Epilepsy

Giulia Salomone; Mattia Comella; Anna Portale; Giulia Pecora; Giuseppe Costanza; Manuela Lo Bianco; Sarah Sciuto; Elena R. Praticò; Raffaele Falsaperla

doi:10.1055/s-0041-1727139

Journal of Pediatric Neurology, Table of Contents

Journal of Pediatric Neurology 2023; 21(04): 248-255
DOI: 10.1055/s-0041-1727139

Review Article

The Spectrum of DEPDC5-Related Epilepsy

Giulia Salomone

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

,

Mattia Comella

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

,

Anna Portale

²Unit of Pediatrics, Avola Hospital, Siracusa, Italy

,

Giulia Pecora

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

,

Giuseppe Costanza

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

,

Manuela Lo Bianco

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

,

Sarah Sciuto

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

,

Elena R. Praticò

³Unit of Pediatrics, Carpi Hospital, Carpi, Italy

,

Raffaele Falsaperla

⁴Unit of Pediatrics and Pediatric Emergency, University Hospital “Policlinico Rodolico-San Marco,” Catania, Italy

⁵Units 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.

Keywords

DEPDC5 - GATOR1 - mTORC1 pathway - mTORopathies - focal epilepsy - focal cortical dysplasia - mTORC1 inhibitors - agonists of GATOR1 - epilepsy surgery

Full Text

References

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