Early onset or syndromic epilepsy

Gene: SCO2

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, 9:08 p.m. | Last Modified: 25 Nov 2019, 9:08 p.m.

Panel Version: 1.456

PMID:18924171 (Verdijk et al, 2008) report compound het SOC2 variants (E140K and W36X) in 2 siblings with fatal infantile cardioencephalomyopathy. The index patient had convulsions age 1 day and died of heart failure age 25 days. The sibling fetus was terminated at 23 weeks following genetic testing.

Created: 21 Nov 2019, 4:42 p.m. | Last Modified: 21 Nov 2019, 4:42 p.m.

Panel Version: 1.423

PMID:10749987 (Jaksch et al., 2000) report 10 patients with fatal hypertrophic cardiomyopathy from 9 families. Mutations in SCO2 (E140K, R171W) were found in 3 patients (2 unrelated families) all of whom had seizures: Table 1.

Created: 21 Nov 2019, 4:36 p.m. | Last Modified: 21 Nov 2019, 4:36 p.m.

Panel Version: 1.423

PMID:10545952 (Papadopoulou et al 1999) identified variants in SCO2 in 3 unrelated infants with fatal cardioencephalomyopathy and COX deficiency. Patient 2 had focal epileptiform discharges on an EEG.

Created: 21 Nov 2019, 4:25 p.m. | Last Modified: 21 Nov 2019, 4:25 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

little evidence to support seizures, however, SCO2 have been reported in patients with mito cytochrome c Oxidase deficiency and neonatal progressive hypertrophic cardiomyopathy . AR fatal infantile cardioencephalomyopathy due to cytochrome C oxidase defic 1 - onset of cardiomyopathy either in utero or first few days of life. Verdijk et al, 2008 - 2 sibs - proband developed seizures after birth and died at age 25 days (sibling terminated during pregnanacy) - both compound het for missense and nonsense. Papadopoulou et al, 1999 - none of the 3 unaff individuals appear to have seizures/epilepsy. Jaksch et al, 2000 - Family B - index cases - both showed seizure like epsiodes. Table in this paper of 10 patients with this syndrome and 7/10 from 6 families had seizures.

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
Cardioencephalomyopathy fatal infantile due to cytochrome c oxidase deficiency, 604377; Myopia, 608908

Publications

• 15210538

Comment when marking as ready: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least four variants reported as compound heterozygotes in three unrelated cases of Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 1, 604377 in which seizures were a phenotypic feature. It appears from the literature that seizures are not commonly reported in this phenotype (PMIDs 14994243, 12020273).

Created: 6 Dec 2018, 11:26 a.m.

Green List (high evidence)

Seizures are part of the phenotype of this metabolic disorder.

Created: 21 Aug 2018, 8:31 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 1, MIM#604377

Publications

• 10545952
• 10749987

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