Early onset or syndromic epilepsy

Gene: COQ4

I don't know

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: Green.

Created: 6 Aug 2019, 8:38 p.m. | Last Modified: 6 Aug 2019, 8:38 p.m.

Panel Version: 1.189

Green List (high evidence)

AR primary coenzyme Q10 defic 7 - Resulting from mitochondrial dysfunction - most patients have onset of severe cardaic or neurologic symptoms soon after birth resulting in death. Brea-Calvo et al, 2015 - 6 patients from 4 unrelated families - severe mito disorder assoc with decreased CoQ10 levels. 2 sibs born of unrelated parents presented with hypotonia, bradycardia and resp insuffic. an unrelated patient died of HCM on first day of life. 2 sibs from a 3rd family had neonatal resp distress, cerebellar hypoplasia, fatal epileptic encephalopathy. Final patient - 18 years old - early norm dev but progressive motor deterioration at 10 months age, seizures at 12 years.Identified 6 diff hom or compound het variants.segregated with the disorder and in vitro func studies done. Chung et al, 2015 - 6 girls from 4 unrelated families - all death between 36 hours-19 months. Common features included encephalopathy with EEG abnormalities, neonatal seizures, cerebellar atrophy and HCM. Identified biallelic missense mutations - segregated with the disorder in families. 2 unrelated patients both of AJ descent had the same R240C variant - consistent with founder effect.

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
Coenzyme Q10 deficiency primary, 616276

Publications

• 25658047

Comment when marking as ready: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least 6 variants reported in unrelated cases in which seizures are a phenotypic feature.

Created: 13 Nov 2018, 1:16 p.m.

Green List (high evidence)

This disorder can present with epileptic encephalopathy.

Created: 12 Aug 2018, 1:57 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Coenzyme Q10 deficiency, primary, 7, MIM#616276

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