Early onset or syndromic epilepsy

Gene: GCH1

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, 8:51 p.m. | Last Modified: 25 Nov 2019, 8:51 p.m.

Panel Version: 1.441

Additional evidence for seizures being part of the metabolic disorder comes from PMID:31202265 (Dayasiri et al, 2019) who report a S. Asian child with AR GTPCH (GCH1) deficiency, diagnosed from metabolic testing and family consanguinity. Features included recurrent seizures since 3 months old.

Created: 21 Nov 2019, 12:12 p.m. | Last Modified: 21 Nov 2019, 12:12 p.m.

Panel Version: 1.409

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

Epilepsy is not one of the cardinal features. AR BH4-deficient hyperphenylalaninemia B - Horvath et al, 2008 - table 1 - seizures reported in GTPCH deficiency with HPA, classic phenotype: AR.

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
Dystonia, DOPA-responsive, with or without hyperphenylalaninemia 128230; Hyperphenylalaninemia, BH4-deficient, B 233910

Publications

• 7730309
• 29948246

Comment on list classification: Changed from Amber to Green. Appropriate phenotype, sufficient cases, and external review comment all support gene-disease association

Created: 20 Nov 2018, 4:54 p.m.

Comment on publications: Added publications to support upgrading of the gene to Green

Created: 20 Nov 2018, 4:52 p.m.

Comment on phenotypes: Added phenotypes suggested from expert review that indicate relevance to inclusion on the Genetic Epilepsy Syndromes panel

Created: 20 Nov 2018, 4:28 p.m.

Green List (high evidence)

Seizures are part of the phenotype of this metabolic disorder.

Created: 14 Aug 2018, 12:48 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Hyperphenylalaninemia, BH4-deficient, B, MIM#233910

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