Early onset or syndromic epilepsy

Gene: SCO1

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, 9:07 p.m. | Last Modified: 25 Nov 2019, 9:07 p.m.

Panel Version: 1.455

PMID:22231385 (Honzik et al., 2012) summarise 461 patients with mitochondrial disorders. One patient had a variant in SCO1: seizures were not a feature (Table 2, Stiburek et al., 2009).

Created: 21 Nov 2019, 4:20 p.m. | Last Modified: 21 Nov 2019, 4:20 p.m.

Panel Version: 1.423

PMID:15023375 (Kurian et al., 2004) report an 8-week old infant who presented with neonatal seizures and limb malformations. There were multiple seizure types, including multifocal myoclonus, complex partial events and generalised tonic–clonic episodes. Treatment of seizures was of limited success. The specific defect seen in the patient was a complex IV deficiency. Although no known variants were identified, the clinical picture overlaps with the SCO1 presentation.

Created: 21 Nov 2019, 4:16 p.m. | Last Modified: 21 Nov 2019, 4:20 p.m.

Panel Version: 1.423

PMID:23878101 (Leary et al., 2013) report compound het variants in SCO1 in a patient with fatal encephalopathy. The patient developed seizures age 4 months which were difficult to control. He died age 5 months (seizure information and extended clinical phenotype is the supporting information).

Created: 21 Nov 2019, 4:09 p.m. | Last Modified: 21 Nov 2019, 4:16 p.m.

Panel Version: 1.422

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

little evidence to support seizures, however, SCO1 have been reported in patients with mito cytochrome c Oxidase deficiency.AR mitochondrial complex IV defic - 3 reported cases - Valnot et al, 2000, Stiburek et al, 2009 & Leary et al, 2003 - none of these papers mention seizures/epilepsy as part of the phenotype.

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
Mitochondrial complex IV deficiency, 220110

Publications

• 19268667
• 11013136

Green List (high evidence)

Seizures are part of the phenotype of this mitochondrial disorder.

Created: 21 Aug 2018, 8:29 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Mitochondrial complex IV deficiency, MIM#220110

Publications

• 23878101
• 11013136
• 19295170

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