Early onset or syndromic epilepsy

Gene: EMX2

There are doubts about the validity of the association of this gene with schizencephaly - see the review on the Intellectual disability panel https://panelapp.genomicsengland.co.uk/panels/285/gene/EMX2/#!review and therefore it should remain amber on the Epilepsy panel.

Created: 30 Sep 2025, 2:19 p.m. | Last Modified: 30 Sep 2025, 2:19 p.m.

Panel Version: 8.37

I don't know

EMX2 is green on the malformations of cortical development panel and since schizencephaly is a developmental birth defect characterised by abnormal slits and clefts in the cerebral hemispheres of the brain - I think it would be more appropriate to be on this panel than on the epilepsy panel and no new evidence from previous review so sticking with amber rating.

Created: 5 Sep 2019, 2:22 p.m. | Last Modified: 5 Sep 2019, 2:22 p.m.

Panel Version: 1.261

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Green List (high evidence)

There is an association between schizencephaly and epilepsy/seizures; did not find further recent literature in addition to what has already been included in reviews below, which appear to meet the PanelApp criteria for a green gene.

Created: 23 Aug 2019, 10:10 a.m. | Last Modified: 23 Aug 2019, 10:10 a.m.

Panel Version: 1.256

I don't know

Schizencephaly - seizures more common with type II. Brunelli et al, 1996 - 3/8 patients with severe schizencephaly were het for diff mutations in EMX2 (type II) - no clinical info provided. Faiella et al, 1997 - 10 additional patients including 2 brothers - 6 het for de novo EMX2 variants - 3 of these (unrelated) had epilepsy. Of note on OMIM they go on to say that other studies with large cohorts of patients with schizencephaly - Tietjen et al, 2007, Merello et al, 2008, Hehr et al, 2010 - no variants identified in this gene and Brunelli and Faiella are part of the same group - ? the functional significance of EMX2 variants and schizencephaly.

Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.

Panel Version: 1.188

Mode of inheritance
Unknown

Phenotypes
Schizencephaly, 269160

I don't know

Comment on list classification: Demoted EMX2 from Green to Amber based on the Webex call on 2019_08_08 for Clinical Indication R59 Early onset or syndromic epilepsy, and the post-Webex review by Helen Lord. The Schizencephaly phenotype is more appropriate for the ID/Cortical malformations panel, and EMX2 has now been added as a Green gene to 'Malformations of cortical development' (#96) panel.

Created: 24 Oct 2019, 12:38 p.m. | Last Modified: 24 Oct 2019, 12:38 p.m.

Panel Version: 1.382

Review and rating collated by Helen Lord (Oxford University Hospitals NHS Foundation Trust, 2019_08_30) on behalf of West Midlands, Oxford and Wessex GLH for GMS Neurology specialist test group. This gene is part of a subset that were re-reviewed following the group Webex call on 2019_08_08 for Clinical Indication R59 Early onset or syndromic epilepsy.

Created: 5 Sep 2019, 2:26 p.m. | Last Modified: 5 Sep 2019, 2:26 p.m.

Panel Version: 1.262

Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Amber.

Created: 6 Aug 2019, 8:38 p.m. | Last Modified: 6 Aug 2019, 8:38 p.m.

Panel Version: 1.189

Comment on list classification: Updated rating from Amber to Green: Green review by Zornitza and 3 cases of Schizencephaly patients with EMX2 variants and partial epilepsy in PMID:9359037. PMID:15921232 (2005) report that half of Schizencephaly patients show epilepsy. Therefore sufficient evidence for inclusion on panel.

Created: 29 Nov 2018, 11:05 a.m.

Faiella et al., 1997 (PMID:9359037) summarise 10 patients with Schizencephaly. 6 patients were heterozygous for de novo variants in EMX2 (including 2 brothers). 3 of these unrelated patients have partial epilepsy (patients VF, MB and PB).

Created: 29 Nov 2018, 11:03 a.m. | Last Modified: 22 Jul 2019, 12:16 p.m.

Panel Version: 1.173

Comment on mode of inheritance: Monoallelic MOI supported by Gene2Phenotype, which provide a 'possible' rating for Familial Schizencephaly.

Created: 29 Nov 2018, 11 a.m.

Green List (high evidence)

Seizures are a feature of this brain development disorder.

Created: 13 Aug 2018, 11:45 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Schizencephaly, MIM#269160

Variants in this GENE are reported as part of current diagnostic practice