Early onset or syndromic epilepsy

Gene: COQ5

I don't know

Comment on list classification: There are 2 unrelated families reported where 5 individuals with biallelic COQ5 variants presented with multifocal epileptiform discharges and seizures. Seizures may be a result of brain atrophy and strokes noted in these patients. Based on available evidence, this gene can only be rated Amber on Early onset or syndromic epilepsy.

Created: 1 Apr 2026, 2:51 p.m. | Last Modified: 1 Apr 2026, 2:51 p.m.

Panel Version: 8.172

PMID: 29044765 Malicdan et al., 2018
Report of 3 female siblings of Iraqi-Jewish descent, who had varying degrees of cerebellar ataxia, encephalopathy, generalized tonic-clonic seizures, and cognitive disability. WES/WGS identified biallelic duplications in the COQ5 gene [Chr12(GRCh37):120940098–120949687]. Sequencing of the cDNA from fibroblasts of patient III.4 shows an abnormal 3′UTR because of an abnormal splicing event, leading to LoF.
Study showed reduced levels of CoQ10 in peripheral white blood cells of all affected individuals and reduced CoQ10 levels in the only muscle tissue available from one affected proband. CoQ10 supplementation led to clinical improvement. Retinal examination not mentioned in report.

PMID: 36266294 Jurkute et al., 2022
2 families, 2 affected individuals with biallelic COQ5 variants and RP
Family 11: 56yo patient with isolated RP (onset at 49 years) - harboured COQ5 variants c.682-7 T > G and c.933delC, p.(Tyr311*).
Family 12: 38 yo patient with RP, nystagmus (onset at 14 yrs), Muscular weakness (hyposthenia) with onset at 5 yrs, as well as infantile appearance, hypertelorism, and undeveloped fertile function. Comp het for COQ5 c.367 C > T, p.(Arg123Trp) and c.682-7 T > G.
c.682-7 T > G variant was confirmed to cause mis-splicing, with exon 5 skipping (p.(Gln230*)), as well as exon 4-5 skipping in a small proportion of reads (p.(Leu193Phefs*27)). Muscle biopsy / fibroblast testing was not done.

PMID: 37599337 Dawidziuk et al., 2023
Report of a patient harbouring one novel c.681+1G>A and one recurrent p.Gly118Ser variant within COQ5. Symptoms included reduced COQ10 levels, intellectual disability, encephalopathy, cerebellar ataxia, cerebellar atrophy speech regression/dysarthria, short stature, and developmental delays, as well as rarer features of dysmorphia, microcephaly, and regressive social faculties. Low COQ10 level tests showing 0.6 mg/l (normal range >0.67 mg/l). Ophthalmologic investigation proved normal.

PMID: 41199775 Wongkittichote et al., 2025
Report of two siblings with profound developmental delay, epilepsy, hypotonia, and stroke‐like episodes - diagnosed with COQ5-related primary CoQ10 deficiency. Clinical exome sequencing revealed compound heterozygous variants in COQ5: c.177_178del (p.Ser60Glyfs13) and c.353G>A (p.Gly118Asp) - confirmed in trans. Brain MRI showed abnormal signal hyperintensity in basal ganglia and thalami, and signs of multiple strokes. Ophthalmologic examination of Patient 1 at the age of 4 years revealed ptosis, pale optic discs concerning for optic atrophy, and abnormal electroretinography consistent with retinopathy. Both patients showed multifocal epileptiform discharges and generalized seizures. COQ10 supplementation yielded subjective improvement in social interaction.

COQ5 is putatively linked to AR ?Coenzyme Q10 deficiency, primary, 9, OMIM:619028 (OMIM accessed 1st Apr 2026). The relationship between COQ5 and mitochondrial disease has been classified as Moderate in ClinGen by Cerebellar Ataxia GCEP in July 2024.
Sources: Literature

Created: 1 Apr 2026, 2:43 p.m. | Last Modified: 1 Apr 2026, 2:48 p.m.

Panel Version: 8.171

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
?Coenzyme Q10 deficiency, primary, 9, OMIM:619028; mitochondrial disease, MONDO:0044970

Publications

• 29044765
• 36266294
• 37599337
• 41199775