Early onset or syndromic epilepsy

Gene: HLCS

I don't know

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. Better tested through the metabolic panel. Demoted from Green to Amber.

Created: 25 Nov 2019, 8:53 p.m. | Last Modified: 25 Nov 2019, 8:53 p.m.

Panel Version: 1.445

PMID:27114915 (Donti et al., 2016) describe a cohort of 5 patients. Case 5 had focal seizures age 5 months which have continued since. He has compound het variants in HLCS (N570K and c.1519+5G>A). The authors note that the phenotypic spectrum of HCLS is broad, from intractable seizures and ID to normal growth and development.

Created: 21 Nov 2019, 2:21 p.m. | Last Modified: 21 Nov 2019, 2:21 p.m.

Panel Version: 1.416

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. 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

I don't know

AR Holocarboxylase synthetase deficiency - charecterised by metabolic acidosis, lethargy, hypotonia, convusions and dermatisis. Most patients present in newborn or early infantile period. Suzuki et al, 2005 - review - 30 mutations reported to date - no detailed clinical info provided. On OMIM no mention of seizures in any of the clinical features described. In Donti et al, 2016 - 5 unrealted patients - 1/5 has seizures. It's possible that early diagnosis and treatment have stopped the development of seizures. Would these all be picked up on newborn biochemical screening ? whether should be in panel.

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
Holocarboxylase synthetase deficiency, 253270

Publications

• 22027809
• 27114915

Comment on list classification: changed rating from Red to Green as suggested by external reviewer. . Publications support gene-disease association and rating of this gene to Green.

Created: 1 Oct 2018, 4:36 p.m.

Green List (high evidence)

Seizures are part of the phenotype in this metabolic disorder.

Created: 15 Aug 2018, 1:24 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Holocarboxylase synthetase deficiency, MIM#253270

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

Red List (low evidence)

Red List (low evidence)

Red List (low evidence)

Red List (low evidence)