Early onset or syndromic epilepsy
Gene: EMX2
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
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
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
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.
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
Gene: emx2 has been classified as Amber List (Moderate Evidence).
Gene: emx2 has been classified as Green List (High Evidence).
Source Wessex and West Midlands GLH was added to EMX2.
Source NHS GMS was added to EMX2.
Zornitza Stark: Seizures are a feature of this
Gene: emx2 has been classified as Green List (High Evidence).
Gene: emx2 has been classified as Green List (High Evidence).
Mode of inheritance for gene: EMX2 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: EMX2 were set to
Phenotypes for gene: EMX2 were changed from to Schizencephaly, 269160
Expert Review Amber was added to EMX2. Panel: Genetic Epilepsy Syndromes
EMX2 was added to Genetic Epilepsy Syndromes panel. Sources: Victorian Clinical Genetics Services
EMX2 was created by Sarah Leigh