Treatment management of mTORopathies: a case report

*Correspondence: [e-mail].

Abstract

Case Presentation: A 16-year-old girl, born to healthy and non-consanguineous parents at 34 weeks, from a twin pregnancy, presented with recurrent focal motor seizures since she was three years old. Her family history of epilepsy was negative. In the complementary investigation, brain MRI was normal, and the electroencephalogram (EEG) showed hyper motor seizures with right frontal or temporal onset. Exome sequencing identified a pathogenic NPRL3 heterozygous variant (NM_001077350.3: c.1032-1G>A). Epilepsy had been pharmacoresistant for many years, despite the use of different antiseizure medication (ASM) in mono or polytherapy. With the use of Vigabatrin, the patient became seizure free and she has been followed with annual electroretinogram.

Discussion: The mammalian target of rapamycin (mTOR) pathways is associated with cell growth and survival, protein synthesis and synaptic plasticity. Variants in genes that correlate with these pathways, such as mTOR, DEPDC5, NPRL3, NPRL2, can lead to intractable epilepsy and developmental delay due to hyperactivation of mTOR signaling. These genes are frequently associated with focal epilepies and eventually with focal cortical dysplasias. Vigabatrin is an ASM with a possible property to suppress the mTOR pathway. Its use to treat focal epilepsies is controvertial due to the high risk of gabaergic retinopathy.

Final Comments: The therapeutic management of mTORopathies must involve therapies that decrease or inhibit the activation of the mTOR pathway, such as the use of vigabatrin, and in cases that present malformations of cortical development, surgical treatment is well established. Despite the risk of side effects with the chronic use of vigabatrin, it should be better evaluated in the mTORopathies associated with pharmacoresistant seizures.

Publication History

Article published online:
12 May 2025