Early onset or syndromic epilepsy

Gene: SLC6A19

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. Epilepsy is not a key feature. Demoted from Green to Red.

Created: 25 Nov 2019, 9:09 p.m. | Last Modified: 25 Nov 2019, 9:09 p.m.

Panel Version: 1.460

PMID:20399395 (Cheon et al 2010) report a Korean boy age 8 years and 5 months with Hartnup disorder. He had seizures, ADHD and mental retardation. Genetic analysis revealed novel compound het variants in SLC6A19: p.Thr596fsX73 and p.Ser303Leu.

Created: 21 Nov 2019, 4:52 p.m. | Last Modified: 21 Nov 2019, 4:52 p.m.

Panel Version: 1.423

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: 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 Hartnup disorder, AD hyperglycinuria and AR & DR digenic Iminoglycinuria. Hartnup disorder - seizures are mentioned as a feature in OMIM but can only see one listed case where the patient had epilepsy. Google search state variable features but not found any specific mentions of epilepsy/seizures. Has a variable phenotype as symptoms triggered by sunlight, fever, drugs or emotional/physical stress - symptoms occur sporadic and are due to a deficiency of the niacin derived enzyme co-factors. Dietary factors also influence presentation as a high protein diet is good (often asymptomatic). Can be diagnosed by a urine/blood tests. Don't add to 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
Hartnup disorder,234500; Hyperglycinuria,138500; Iminoglycinuria, digenic,242600

Publications

• 24596948
• 15592994

Green List (high evidence)

Seizures listed as a clinical feature of Hartnup disorder 234500, considered to be appropriate by Dr Arianna Tucci (Neurology, UCL). Associated with phenotypes in OMIM, not in G2P / DD. At least 6 variants reported in 8 cases of Hartnup disorder 234500

Created: 6 Feb 2017, 10:44 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Hartnup disorder 234500

Publications

• 27604308
• 20399395
• 19335424