Compound heterozygous SZT2 mutations in two siblings with early-onset epilepsy, intellectual disability and macrocephaly

Francisco S Domingues (Corresponding author), Eva König, Christine Schwienbacher, Claudia B Volpato, Anne Picard, Chiara Cantaloni, Deborah Mascalzoni, Peter Lackner, André Heimbach, Per Hoffmann, Franco Stanzial, Andrew A Hicks, Lucio Parmeggiani, Francesco Benedicenti, Serena Pellegrin, Gianluca Casara, Peter P Pramstaller

Research output: Contribution to journalArticle


PURPOSE: Mutations in SZT2 have been previously reported in several cases of early onset epilepsy and intellectual disability. In this study we investigate potential causal mutations in two male siblings affected by early onset epilepsy, intellectual disability and macrocephaly.

METHODS: We use family-based whole-exome sequencing to identify candidate variants.

RESULTS: We report the identification of two potential causal SZT2 mutations in compound heterozygous state. We observe considerable differences in the clinical phenotype severity of the two affected individuals. The cerebral MRI revealed no abnormalities in the older affected brother, while in the youngest one it revealed a right frontal polymicrogiria. Moreover, while good seizure control was achieved in the older affected individual the younger brother is affected by pharmacoresistant epilepsy, progressive spastic paraplegia, cortical myoclonus and a more severe intellectual disability. We also analyzed the relative location of the reported pathogenic mutations in the SZT2 protein.

CONCLUSION: Variable phenotypic expressivity is observed for this condition, while the location and type of mutations in SZT2 also has a potential impact on epilepsy severity. These findings extend our knowledge of epileptogenic conditions related to SZT2 and mTOR signaling.

Original languageEnglish
Pages (from-to)81-85
Number of pages5
JournalSeizure : the journal of the British Epilepsy Association
Publication statusPublished - Mar 2019

Bibliographical note

Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.

Fields of Science and Technology Classification 2012

  • 106 Biology
  • 302 Clinical Medicine
  • 102 Computer Sciences


  • Adult
  • DNA Mutational Analysis
  • Epilepsy/complications
  • Family Health
  • Humans
  • Intellectual Disability/complications
  • Longitudinal Studies
  • Magnetic Resonance Imaging
  • Male
  • Megalencephaly/complications
  • Mutation/genetics
  • Nerve Tissue Proteins/genetics
  • Whole Exome Sequencing
  • Young Adult

Cite this

Domingues, F. S., König, E., Schwienbacher, C., Volpato, C. B., Picard, A., Cantaloni, C., Mascalzoni, D., Lackner, P., Heimbach, A., Hoffmann, P., Stanzial, F., Hicks, A. A., Parmeggiani, L., Benedicenti, F., Pellegrin, S., Casara, G., & Pramstaller, P. P. (2019). Compound heterozygous SZT2 mutations in two siblings with early-onset epilepsy, intellectual disability and macrocephaly. Seizure : the journal of the British Epilepsy Association, 66, 81-85.