Early onset or syndromic epilepsy

Gene: FARS2

Green List (high evidence)

AR combined oxidative phosphorylation defic 14 - neonatal onset of dev delay, refractory seizures and lactic acidosis. Shamseldin et al, 2012 - consang S. Arabian family - all 3 sibs had seizures and all died in forst couple of years of life - hom missense variant. Elo et al, 2012 - Finish family - 2 sisters - proband developed treatment-resistant myoclonic seizures on day 2 of life - older sister had a sim phenotype - compound het for two missense variants. Almaki et al 2014 - 2.5 year old boy born of unrelated British Caucasian parents with onset of severe seizures - compound het for missense and an 88kb interstitial del, in vitro studies done. Waker et al, 2016 - girl with severe juvenille-onset epileptic encehalopathy - compound het missense variants and in vitro studies done.

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 14, 614946; Spastic paraplegia 77, 617046

Publications

• 24161539
• 29126765

I don't know

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 by Zornitza- seizures are a common phentoype of MIM:614946. Plenty of unrelated (>3) cases of seizures in FARS2 patients from the literature (PMIDs 24161539, 22833457, 22499341, 28043061) as summarised in PMID:29126765.

Created: 29 Nov 2018, 1:59 p.m.

PMID:22499341 (Shamseldin et al 2012) report an index patient and her two siblings with a homozygous FARS2 variant c.431A>G (p.Y144C). The patients had uncontrolled seizures starting in infancy.

Created: 29 Nov 2018, 1:54 p.m.

Cho et al, 2017 (PMID:28043061) report a novel homozgyous c.925G>A (G309S) missense variant in FARS2 in 4 patients from 2 nonconsanguineous Korean families. All 4 patients had intractable seizures.

Created: 29 Nov 2018, 1:54 p.m.

PMID:22833457 (Elo et al 2012) discovered compound het FARS2 variants in two siblings with fatal epileptic mitochondrial encephalopathy (p.I329T and p.D391V).

Created: 29 Nov 2018, 1:53 p.m.

Almalki et al. (2014, PMID: 24161539) report a young boy born to unrelated British Caucasian parents. He demonstrated refractory seizures, developing into focal seizures and had a heterozygous c.973G-T, NM_006567.3 (D325Y) maternally-inherited variant in FARS2 plus a paternally-inherited 88kb deletion of chromosome 6p25.1 including the promotor and UTR of FARS2, and the 3' exons of LYRM4 gene.

Created: 29 Nov 2018, 1:53 p.m.

Green List (high evidence)

Seizures are a prominent feature of the phenotype.

Created: 13 Aug 2018, 12:25 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Combined oxidative phosphorylation deficiency 14, MIM#614946

Publications

• 24161539, 22833457, 22499341, 29126765

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