In this study, regarding a homozygous truncating <i>RNF43</i> variant (NM_001305545.1:c.1906C>T; p.Gln636Ter) in a patient segregating with a severe neurodevelopmental phenotype characterized by developmental delay, neonatal hypotonia, recurrent seizures, progressive microcephaly, and bilateral optic atrophy, the loss of polarity defective 1 (<i>plr-1</i>), an ortholog of <i>RNF43</i>, was modeled in <i>Caenorhabditis elegans</i> and the phenotype was primarily characterized. The gene discussed is RNF43; the disease is hereditary optic atrophy.