New genotype-phenotype correlations in recessive Leber hereditary optic neuropathy

Abstract

Purpose : To assess the clinical and structural optical coherence tomography (OCT) findings in patients with Leber hereditary optic neuropathy (LHON) due to recessive mutations as compared with mitochondrial DNA (mtDNA)-LHON.

Methods : Three patients with DNAJC30 recessive mutation, 2 patients with MECR recessive mutation, and 1 patient with NDUFAF4 recessive mutation were assessed clinically and analysed by OCT, compared with the natural history of classical mtDNA-LHON disease.

Results : The patients with MECR and NDUFAF4 mutations showed an insidious onset of visual loss in childhood followed later by subacute visual loss in adult age. Reduced thickness of temporal retinal nerve fibre layer (RNFL) and ganglion cell layer (GCL) were evident since childhood in one case, preceding the adult onset decline of visual function. The DNAJC30 patients presented childhood onset in one case and adult onset in 2 cases, the latter with typical LHON fundus appearance characterized by RNFL swelling and microangiopathy at the optic nerve head.

Conclusions : The recessive LHON with MECR and NDUFAF4 mutations showed a clinical picture distinct from the classic mtDNA-LHON, whereas recessive LHON with DNAJC30 mutation had a clinical presentation undistinguishable from classic mtDNA-LHON. We propose to define LHON-like the recessive forms of inherited recessive optic neuropathy, as a distinct clinical picture may occur, whereas DNAJC30-LHON- is confirmed to closely resemble the classic mtDNA-LHON.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.