Early onset or syndromic epilepsy
Gene: IDH2
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Refers to glioma patients- not a seizure disorder. Demoted from Green to RED.Created: 25 Nov 2019, 8:54 p.m. | Last Modified: 26 Nov 2019, 4:10 p.m.
Panel Version: 1.475
A number of papers note that IDH1 and IDH2 variants have an established association with preoperative seizures in patients with grade II-IV diffuse gliomas (PMID:29172136, 29288860, 22217666).Created: 21 Nov 2019, 2:44 p.m. | Last Modified: 21 Nov 2019, 2:44 p.m.
Panel Version: 1.417
PMID:24049096 (Nota et al., 2013) report 3 cases, with seizures reported in 2/3. Case 2 was a 9 year old Caucasian girl with tonic-clonic seizures and mosaic IDH2 variants. Case 3 was a Caucasian girl with seizures age 3 months- her seizures responded well to anticonvulsants. The patient died from sudden cardiac arrest age 8, and was found to have a heterozygous IDH2 c.419G>A variant. Germline mosaicism in the mother was suggested to explain the inheritance pattern in this family.Created: 21 Nov 2019, 2:41 p.m. | Last Modified: 21 Nov 2019, 2:41 p.m.
Panel Version: 1.416
Comment on mode of inheritance: Kept Mode of Inheritance as MONOALLELIC based on post-Webex review from Helen Lord. Note that the rating of IDH2 was not discussed on the group Webex (2019_08_08 for Clinical Indication R59 Early onset or syndromic epilepsy) because IDH2 has a Green rating on the 'Inborn errors of metabolism' panel, and therefore will be Green on the Epilepsy super panel for R59.Created: 7 Sep 2019, 10:56 a.m. | Last Modified: 7 Sep 2019, 10:56 a.m.
Panel Version: 1.278
Mode of inheritance 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 where the mode of inheritance was re-reviewed following the group Webex call on 2019_08_08 for Clinical Indication R59 Early onset or syndromic epilepsy. No rating was included in the review, so I have uploaded an Amber rating to match the original West Midlands, Oxford and Wessex GLH rating.Created: 5 Sep 2019, 2:26 p.m. | Last Modified: 5 Sep 2019, 2:26 p.m.
Panel Version: 1.262
Comment on mode of inheritance: The mode of inheritance for IDH2 is currently MONOALLELIC on the 'Intellectual disability' panel, and the 'Inborn errors of metabolism' panel.Created: 13 Aug 2019, 12:59 p.m. | Last Modified: 13 Aug 2019, 12:59 p.m.
Panel Version: 1.206
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
Cancer association. ?Consent. AD D-2-hydroxyglutaric acidurea 2 (D2HGA2) - Kranendijk et al, 2010 - phenotypically characterised 17 unrelated patients with D-2-hydroxyglutaric acidurea (phentype ranged from asymp to dev delay, epilepsy, hypotonia, cardiomyopathy and dysmoprhic features) who didn't have a mutation in the D2HGDH gene - 15/17 had mutations in the IH2 gene - 14 R140Q and 1 R140G, and arose de novo in 8/9 cases. In 1 family mother had 3 aff pregnancies and was shown to be a somatic mosaic. Functional studies have been done (2011).Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.
Panel Version: 1.188
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Comment on mode of inheritance: Changed from 'other' to monoallelic, due to reports of heterozygous variants to enable variants in this gene to be tiered.Created: 5 May 2017, 7:41 a.m.
Comment on mode of inheritance: >3 cases including PMID:20847235 who detected heterozygous germline variants in IDH2 that alter Arg140 in 15 unrelated patients with MIM:613657; in 14 cases the variant was de novo. The mother of 1 patient demonstrated germline mosaicism. PMID:24049096 also report a heterozygous IDH2 and the unaffected mother was a mosaic carrier. Somatic variants also reported.Created: 20 Mar 2017, 12:19 p.m.
Inclusion of this as a green gene on this panel is appropriate, based on the review in the Undiagnosed metabolic disorders panel and the views of clinical expert, Dr Arianna Tucci, UCL.Created: 20 Mar 2017, 12:18 p.m.
Mode of inheritance
Other
Phenotypes
D-2-hydroxyglutaric aciduria 2 613657
Publications
Gene: idh2 has been classified as Red List (Low Evidence).
Publications for gene: IDH2 were set to 20847235
Gene: idh2 has been classified as Green List (High Evidence).
Mode of inheritance for gene: IDH2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mode of inheritance for gene: IDH2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: IDH2 were changed from D-2-hydroxyglutaric aciduria 2 to D-2-hydroxyglutaric aciduria 2, 613657
Publications for gene: IDH2 were set to
Source Wessex and West Midlands GLH was added to IDH2.
Source NHS GMS was added to IDH2.
Sarah Leigh: Inclusion of this as a green g
IDH2 was added to Genetic Epilepsy Syndromes panel. Sources: Expert Review Green,Expert Review
IDH2 was created by Sarah Leigh