Early onset or syndromic epilepsy
Gene: EFHC1
This gene appears to be associated with various epilepsy phenotypes, and the evidence comes from various sources. Additionally, there are several cases of EFHC1 being associated with juvenile myoclonic epilepsy in PMID 28370826.Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.
Panel Version: 1.188
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
{Epilepsy, juvenile absence, susceptibility to, 1}, 607631 ; {Myoclonic epilepsy, juvenile, susceptibility to, 1}, 254770
Publications
As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that this gene should remain as Amber: EFHC1 may be a susceptibility locus. Currently insufficient evidence to support a monogenic association with epilepsy.Created: 13 Aug 2019, 4:15 p.m. | Last Modified: 15 Aug 2019, 8:05 a.m.
Panel Version: 1.222
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: Alison Callaway and John Taylor. Suggested gene rating: Green.Created: 6 Aug 2019, 8:38 p.m. | Last Modified: 6 Aug 2019, 8:38 p.m.
Panel Version: 1.189
PMID:29750216: Thounaojam et al., 2017 studied 63 Indian patients from 63 independent families with Juvenile myoclonic epilepsy (JME) and found 4 heterozygous coding variants (R221C, R260Q, R294H and R244STOP) and 1 homozygous and one heterozygous coding variant (R159W, which is considered a polymorphism). Lack of family samples meant the mode of inheritance couldn't be followed up.Created: 1 Jul 2019, 1:09 p.m. | Last Modified: 1 Jul 2019, 1:09 p.m.
Panel Version: 1.85
PMID:31056551: Heyne et al., 2019 performed a large-scale analysis of previously-sequenced variants in individuals with a 'neurodevelopmental disorder with epilepsy. They show that EFHC1 showed equal frequencies of ultra-rare variants in cases and controls supporting the existing evidence that EFHC1 may not be truly associated with epilepsy.Created: 1 Jul 2019, 1:09 p.m. | Last Modified: 1 Jul 2019, 1:09 p.m.
Panel Version: 1.85
PMID:28370826. Raju et al., 2017 examine 480 Juvenile myoclonic epilepsy patients from India, and identified 13 variants (11 of which were novel, 10 of which are predicted to be pathogenic) in 28 JME patients. They were absent or uncommon among controls. All variants were missense. Patients with family histories of progressive myoclonic epilepsy (PME) were not included in the study. The authors submitted their variants to LOVD, including 14 polymorphisms that were common in controls and databases (https://databases.lovd.nl/shared/variants/EFHC1/unique).Created: 1 Jul 2019, 1:08 p.m. | Last Modified: 1 Jul 2019, 1:08 p.m.
Panel Version: 1.85
Comment on list classification: As this gene is associated with susceptibility to juvenile absence epilepsy (MIM 607631) and juvenile myoclonic epilepsy 1 (MIM 254770), EFHC1 has been rated at amber in consultation with Arianna Tucci (GEL Clinical Fellow).Created: 14 Nov 2018, 9:06 p.m.
Comment on list classification: Associated with phenotype in OMIM and not in Gen2Phen. At least 7 variants identified in unrelated cases, due to issues of penetrance the pathogenicity classification of the variants is not well established. However, a null mouse model is supportive of the association of EFHC1 with epilepsy (PMID 19147686).Created: 21 Jun 2018, 8:41 a.m.
Gene: efhc1 has been classified as Amber List (Moderate Evidence).
Source Wessex and West Midlands GLH was added to EFHC1.
Source NHS GMS was added to EFHC1.
Publications for gene: EFHC1 were set to 17159113; 18505993; 15258581; 19147686; 28370826
Publications for gene: EFHC1 were set to 17159113; 18505993; 15258581; 19147686
Sarah Leigh: Comment on list classification
Gene: efhc1 has been classified as Amber List (Moderate Evidence).
Gene: efhc1 has been classified as Amber List (Moderate Evidence).
Gene: efhc1 has been classified as Green List (High Evidence).
NIHRBR-RD Consortium SPEED_v3.0_20170404 was added to EFHC1. Panel: Genetic Epilepsy Syndromes
Gene: efhc1 has been classified as Amber List (Moderate Evidence).
Expert list was added to EFHC1. Panel: Genetic Epilepsy Syndromes Phenotypes for gene EFHC1 were set to {Epilepsy, juvenile absence, susceptibility to, 1} 607631, {Myoclonic epilepsy, juvenile, susceptibility to, 1} 254770
Source Expert was removed from EFHC1. Panel: Genetic Epilepsy Syndromes Literature was added to EFHC1. Panel: Genetic Epilepsy Syndromes Phenotypes for gene EFHC1 were set to {Epilepsy, juvenile absence, susceptibility to, 1} 607631, {Myoclonic epilepsy, juvenile, susceptibility to, 1} 254770 Penetrance for gene EFHC1 was set to Incomplete
Phenotypes for gene: EFHC1 were set to {Epilepsy, juvenile absence, susceptibility to, 1} 607631; {Myoclonic epilepsy, juvenile, susceptibility to, 1} 254770
Publications for gene: EFHC1 were set to 17159113; 18505993; 15258581; 19147686
Mode of inheritance for gene: EFHC1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Gene: efhc1 has been classified as Amber List (Moderate Evidence).
EFHC1 was added to Genetic Epilepsy Syndromes panel. Sources: Expert,Expert Review Red
EFHC1 was created by Sarah Leigh