Early onset or syndromic epilepsy

Gene: ACOX1

The mode of inheritance of this gene has been updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.

Created: 1 Feb 2023, 9:39 a.m. | Last Modified: 1 Feb 2023, 9:39 a.m.

Panel Version: 3.29

PMID: 32169171. 3 unrelated patients with the same de novo variant (N237S) with a progressive disease. Age of onset is between 3-12 years old (cf to AR patients 0-3 years old), disease course is progressive (AR patients, early onset and severe) white matter demyelination is progressive, sensorineural hearing loss and ataxia. Authors found that the variant increased levels of ACOX1 protein and function which increased levels of ROS in glia of Drosphila and mouse Schwann cells leading to glial degeneration. The authors suggested that the variant caused a GOF effect. AD causes Mitchell syndrome (OMIM:618960) and AR causes Peroxisomal acyl-CoA oxidase deficiency (OMIM:264470).

Therefore, MOI should be changed from Biallelic to Both monoallelic and biallelic (but biallelic mutations cuase a more severe disease form).

Created: 5 Jul 2021, 9:01 a.m. | Last Modified: 5 Jul 2021, 9:01 a.m.

Panel Version: 2.384

Mode of inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal

Phenotypes
Mitchell syndrome, OMIM:618960

Publications

• 32169171

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 Peroxisomyl acyl-CoA oxidase deficiency.Newborns withperoxisomal acyl-CoA oxidase deficiencyhave weak muscle tone (hypotonia) and seizures. They may have unusual facial features, including widely spaced eyes (hypertelorism), a low nasal bridge, and low-set ears. Extra fingers or toes (polydactyly) or an enlarged liver (hepatomegaly) also occur in some affected individuals.Fournier et al, 1994 - large del in the ACOX1 gene in 2 sibs. Suzuki et al, 2002 - hom mutation identified in 2 Japanese sibs, and a diff hom variant identified in anothe aff Japanese child. Ferdinandusse et al, 2007- 20 diff mutations in ACOX1 in 22 aff patients 92 were sibs), 91% presented with seizures in the 11 patients who provided this information.

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
Peroxisomal acyl-CoA oxidase deficiency, 264470

Publications

• 18536048

Green List (high evidence)

seizures are part of the phenotype. enough evidence to mark as green

Created: 29 Jun 2018, 1:49 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Peroxisomal acyl-CoA oxidase deficiency, 264470