Early onset or syndromic epilepsy

Gene: AMACR

Green List (high evidence)

Comment on list classification: More than 50% of patients with biallelic AMACR variants present with seizures / have an epilepsy diagnosis. Based on available evidence, AMACR is tagged for promotion to Green on Early onset or syndromic epilepsy at the next update. As the seizures may be caused by pathological brain lesions, the gene is also tagged for expert review, to ascertain whether this gene is in scope of testing.

Created: 17 Mar 2026, 4:46 p.m. | Last Modified: 17 Mar 2026, 4:46 p.m.

Panel Version: 8.152

PMID: 37452652 Palacio-Montoya et al., 2023
3 sibs with recurrent episodes of encephalopathy, seizures, and behavioural disturbances. In all 3, brain MRI showed lesions in the thalami, cerebral peduncles, and mesencephalic tegmentum, as well as brain volume loss. Homozygous AMACR c826 G>C p.Ala276Pro variant detected in affected individuals.

In a literature review in the same paper, 9/16 previously reported patients with AMACR deficency had seizures / epilepsy, which correlated with abnormal brain MRI findings. The most common variant was c.154T>C, p.Ser52Pro (7/16 patients).
Sources: Literature

Created: 17 Mar 2026, 4:40 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Alpha-methylacyl-CoA racemase deficiency, OMIM:614307

Publications

• 37452652