Insight into Genetic Mutations of SZT2: Is It a Syndrome?

Area of Science:

• Genetics
• Neuroscience
• Molecular Biology

Background:

• The seizure threshold 2 (SZT2) gene encodes a protein involved in the KICSTOR complex, regulating mTORC1 signaling.
• Pathogenic variants in SZT2 can lead to hyperactive mTORC1 signaling, associated with various neurological disorders.

Purpose of the Study:

• To review existing literature on SZT2 mutations and present two new cases.
• To expand the understanding of SZT2-related neurological conditions.

Main Methods:

• Whole exome sequencing (WES) was employed to identify novel cases.
• Literature review and comparative analysis of clinical, genetic, neuroimaging, and electrophysiological data.

Main Results:

• The study analyzed 29 patients (16 female, 13 male) with SZT2 mutations, including two novel male cases.
• Predominant findings included facial dysmorphism (n=22), seizures (n=26), developmental delay (n=27), and hypotonia (n=15).
• EEG revealed multifocal epileptiform discharges, and MRI showed a short, thick corpus callosum in most patients.

Conclusions:

• Facial dysmorphism and developmental delay are emerging as potential hallmarks for SZT2 mutations.
• High variability exists among patients with SZT2 mutations, necessitating careful clinical evaluation.
• Identifying these features can aid in earlier diagnosis and improved management of SZT2-related disorders.