Early onset or syndromic epilepsy

Gene: KARS

Added new-gene-name tag, new approved HGNC gene symbol for KARS is KARS1

Created: 6 Sep 2019, 12:07 p.m. | Last Modified: 6 Sep 2019, 12:07 p.m.

Panel Version: 1.263

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

Green List (high evidence)

AR deafness and AR intermed ? CMT disease B. No merntion of seizures as a feature on OMIM with either of these diseases. Refs from panel app: Ardisonne et al, 2018 - 11 families/sporadic patients reported to date and this equates to 16 diff mutations. In this paper they describe 3 unrelated patients and put clinical info of all reported patients together. 27 patients in total: 8 are said to have seizures. Murray et al, 2017 - patient 23 reported in the Ardisonne et al paper - seizures mentioned in this paper, in this paper they say seizures have been a feature in 25% (8 cases). Ruzzenente et al, 2018 - Girl of French origin non-consng parents - compound het for a missense and a fs variant. No mention of seizures/epilepsy. %age of cases with epilepsy 29%.

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
?Charcot-Marie-Tooth disease, recessive intermediate, 613641; Deafness, 613916

Publications

• 29615062

Comment when marking as ready: Although seizures are not present in all cases of ?Charcot-Marie-Tooth disease, recessive intermediate, B 613641 or Deafness, autosomal recessive 89 613916, seizures have been reported in at least 5 cases carrying a total of 10 KARS variants AS compound heterozygotes.

Created: 7 Nov 2018, 1:55 p.m.

Green List (high evidence)

Several individuals with biallelic pathogenic variants in KARS have been reported (summarized in PMIDs : 29615062, 30252186, 28496994).

Developmental delay and/or intellectual disability are among the (most) frequent features, although not universal.

Seizures are part of the phenotype (15-30% of the individuals) according to the tables provided in these 3 publications.

As a result it can be considered for inclusion in the epilepsy panel as green (or amber).
Sources: Literature, Expert Review

Created: 17 Oct 2018, 12:17 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Global developmental delay; Intellectual disability; Seizures; Charcot-Marie-Tooth disease, recessive intermediate, B - 613641; Deafness, autosomal recessive 89 - 613916

Publications

• 29615062
• 30252186
• 28496994