We report nine individuals from six unrelated families presenting with bi-allelic SNF8 (MIM: 610904) variants and a spectrum of neurodevelopmental/neurodegenerative phenotypes, including lethal developmental and epileptic encephalopathy with leukoencephalopathy, optic atrophy with intellectual disability (ID), and ataxia. This evidence concerns the gene SNF8 and Leber hereditary optic neuropathy.