Combined oxidative phosphorylation deficiency type 7 (COXPD7) is a rare disorder 
of mitochondrial metabolism that results in optic atrophy and Leigh 
syndrome-like disease. We describe 2 siblings with compound heterozygous 
mutations in the recently identified C12orf65 gene who presented with optic 
atrophy and mild developmental delays and subsequently developed bilateral, 
symmetric lesions in the brainstem reminiscent of Leigh syndrome. Repeat 
neuroimaging demonstrated reversibility of the findings in 1 sibling and 
persistent metabolic stroke in the other. This article highlights the phenotypic 
manifestations from a novel mutation in the C12orf65 gene and reviews the 
clinical presentation of the 5 other individuals reported to date who carry 
mutations in this gene.