Early onset or syndromic epilepsy
Gene: EARS2
AR Combined oxidative phosphorylation defic 12 - mitochondrial neurologic disorder characterised by onset in infancy of hypotonia and delayed psychomotor development or early developmental regression. Steenweg et al, 2012 - 6 year old Italian boy - seizures developed at 6 months of age. Identified an additional 11 patients with similar pheno, incl 2 aff brothers. 4 patients - severe - all had epilespy, 8 patients - mild - some had epilepsy (2/6). All patients found to have compound het variants. Taim et al, 2013 - male infant born to consang parents - no seizures but died at 3 months of age - hom variant detected.Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.
Panel Version: 1.188
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Combined oxidative phosphorylation deficiency, 614924
Publications
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: Green.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 from Zornitza plus sufficient cases (>3) of seizures and/or epilepsy in patients from the literature (PMIDs:22492562, 26619324, 27117034, 27206875) for inclusion on panel.Created: 26 Nov 2018, 11:22 a.m.
Oliveira et al (PMID:27571996, 2017) review cases of patients with EARS2 variants (Supplementary material). Seizures and/or Epilepsy are recorded in Patients 1 and 9 from Steenwag et al., 2012 (PMID:22492562), Kevelam et al 2016 (PMID:26619324), Gungor et al, 2016 (PMID:27117034) and Sahin et al., 2016 (PMID:27206875). Note that Sahin et al., 2016 (PMID:27206875) report clinical findings for two siblings with pathogenic variants in EARS2; only the younger brother had seizures amongst his symptoms.Created: 26 Nov 2018, 11:16 a.m.
Seizures are a common feature of this metabolic disorder.Created: 13 Aug 2018, 11:23 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Combined oxidative phosphorylation deficiency 12, MIM#614924
Publications
Variants in this GENE are reported as part of current diagnostic practice
Source Wessex and West Midlands GLH was added to EARS2.
Source NHS GMS was added to EARS2.
Zornitza Stark: Seizures are a common feature
Gene: ears2 has been classified as Green List (High Evidence).
Gene: ears2 has been classified as Green List (High Evidence).
Publications for gene: EARS2 were set to
Phenotypes for gene: EARS2 were changed from Combined oxidative phosphorylation deficiency 12, 614924; Leukoencephalopathy with thalamus and brainstem involvement and high lactate (LTBL) to Combined oxidative phosphorylation deficiency 12, 614924; Leukoencephalopathy with thalamus and brainstem involvement and high lactate (LTBL); Drug-refractory seizures; Epilepsy
Phenotypes for gene: EARS2 were changed from Combined oxidative phosphorylation deficiency 12, 614924 to Combined oxidative phosphorylation deficiency 12, 614924; Leukoencephalopathy with thalamus and brainstem involvement and high lactate (LTBL)
Mode of inheritance for gene: EARS2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: EARS2 were changed from to Combined oxidative phosphorylation deficiency 12, 614924
Expert Review Amber was added to EARS2. Panel: Genetic Epilepsy Syndromes
EARS2 was added to Genetic Epilepsy Syndromes panel. Sources: Victorian Clinical Genetics Services
EARS2 was created by Sarah Leigh