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Journal of Pediatric Neurology 2023; 21(04): 235-247
DOI: 10.1055/s-0041-1727142
Review Article

TSC1 and TSC2: Tuberous Sclerosis Complex and Its Related Epilepsy Phenotype

Claudia Di Napoli‡   *
1   Postgraduate Training Program in Genetics, Department of Biomedical and Biotechnological Sciences, Section of Genetics, University of Catania, Catania, Italy
,
Alessia Gennaro‡   *
1   Postgraduate Training Program in Genetics, Department of Biomedical and Biotechnological Sciences, Section of Genetics, University of Catania, Catania, Italy
,
Carmelania Lupica‡   *
1   Postgraduate Training Program in Genetics, Department of Biomedical and Biotechnological Sciences, Section of Genetics, 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 Intenstive Care and Neonatology, University Hospital “Policlinico Rodolico-San Marco,” Catania, Italy
,
Roberta Leonardi
4   Department of Clinical and Experimental Medicine, Section of Pediatrics and Child Neuropsychiatry, Unit of Rare Diseases of the Nervous System in Childhood, University of Catania, Catania, Italy
,
Maria Teresa Garozzo
5   Unit of Pediatrics and Pediatric Emergency, Hospital “Cannizzaro,” Catania, Italy
,
Agata Polizzi
6   Chair of Pediatrics, Department of Educational Sciences, University of Catania, Catania, Italy
,
Andrea D. Praticò 
4   Department of Clinical and Experimental Medicine, Section of Pediatrics and Child Neuropsychiatry, Unit of Rare Diseases of the Nervous System in Childhood, University of Catania, Catania, Italy
,
Antonio Zanghì
7   Department of General Surgery and Medical-Surgical Specialty, University of Catania, Catania, Italy
,
Martino Ruggieri
6   Chair of Pediatrics, Department of Educational Sciences, University of Catania, Catania, Italy
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Abstract

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by a multisystemic involvement. In TSC, reduced function of TSC1 and TSC2 genes products (hamartin and tuberin, respectively) leads to an hyperactivation of the mechanistic target of rapamycin (mTOR) pathway and to a consequent cell growth dysregulation. In TSC patients, neurological and neuropsychiatric manifestations, especially epilepsy and neuropsychiatric comorbidities such as autism or intellectual disability, represent the most disabling features. In particular, epilepsy occurrs up to 80% of patients, is often drug resistant and is frequently associated with neurological impairment. Due to the burden of this morbidity, different treatment strategies have been proposed with the purpose to make patients epilepsy free, such as the use of different antiepileptic drugs like vigabatrin, carbamazepine, valproic acid, and levetiracetam. More recently, a mTOR inhibitor (i.e. everolimus) has showed promising results in terms of seizures reduction.

Keywords

TSC1 - TSC2 - tuberous sclerosis complex - epilepsy - vigabatrin - everolimus

* The authors have equally contributed to this article.




Publication History

Received: 20 February 2021

Accepted: 21 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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