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Case Reports
. 2024 Sep 6;25(17):9676.
doi: 10.3390/ijms25179676.

A New De Novo Missense Variant of the TET3 Gene in a Patient with Epilepsy and Macrocephaly

Miryam Rosa Stella Foti  1 , Maria Giovanna Tedesco  2   3 , Davide Colavito  4 , Daniela Rogaia  3 , Amedea Mencarelli  3 , Monica Schippa  3 , Cristina Gradassi  3 , Rita Romani  3   5 , Carmela Ardisia  3 , Paolo Prontera  3
Affiliations
Case Reports

A New De Novo Missense Variant of the TET3 Gene in a Patient with Epilepsy and Macrocephaly

Miryam Rosa Stella Foti et al. Int J Mol Sci. .

Abstract

The etiology of neurodevelopmental disorders and epilepsy is very heterogeneous and partly still unknown, and the research of causative genes related to these diseases is still in progress. In 2020, pathogenic variants of the TET3 gene were associated with Beck-Fahrner syndrome, which is characterized by neurodevelopmental delay, intellectual and learning disabilities of variable degree, growth abnormalities, hypotonia and seizures. Variants of TET3 have been described having both an autosomal dominant with a milder phenotype and an autosomal recessive pattern. To date, in the literature, only 28 patients are reported with pathogenic variants of the TET3 gene, and only 9 of them have epilepsy. We describe a 31-year-old woman with macrocephaly, mild neurodevelopmental delay and a long history of epilepsy. Trio-based exome sequencing identified a de novo heterozygous TET3 variant, c.2867G>A p.(Arg956Gln), never described before, absent in the general population and predicted to be potentially pathogenetic by bioinformatics tools. This report aims to describe the clinical history of our patient, the pharmacological treatment and clinical response, as well as the biological characteristics of this new variant.

Keywords: TET3; dysarthria; epilepsy; macrocephaly.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Brain MRI of the proband performed at 18 years of age, with (a) no significant malformation in the sagittal plane, white arrow indicates the small expansion of the periencephalic liquor spaces (b) asymmetry of the occipital lobes in the coronal plane (c) white arrow indicates the asymmetry of the occipital lobes in the axial plane.
Figure 2
Figure 2
A routine surface EEG of the patient at 14 years old, using the 10/20 international system, in bipolar montage shows electrical status epilepticus during slow-wave sleep (ESES).
Figure 3
Figure 3
Schematic presentation of TET3 protein structure and pathogenic variants previously described; in orange, variants in patients with an epilepsy phenotype, in red the novel variant. Adapted from Sager et al. [2].
Figure 4
Figure 4
Facial appearance of the patient at the age of 32 years: tall and broad forehead, long face, epicanthal folds, arched eyebrows, simplified ears, broad nose with smooth philtrum.
See this image and copyright information in PMC

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