Phenotypic Exploration in Patients with Heterozygous Variant in <scp> <i>AFG3L2</i> </scp> Gene: A Case‐Series and Literature Review

BACKGROUND: Variants in AFG3-Like Matrix AAA Peptidase, Subunit 2 (AFG3L2) gene are associated with diverse clinical phenotypes. Here, we describe phenotypic findings of two unrelated children with de novo heterozygous variant and one family with inherited heterozygous variant in AFG3L2 gene. CASES: A 3-year-old girl presented with global developmental delay, vision disturbances and frequent falls. She developed choreoathetosis, feeding difficulty and sleep disturbances from 3.5 years of age. Developmental regression, and optic atrophy were identified. An 11-year-old girl presented with left foot dystonia and tremulousness at 2 years of age which later progressed to developmental regression and generalized dystonia. Bilateral optic disc pallor was observed. In contrast, spinocerebellar ataxia 28 phenotype with variable expressivity was observed in adult patients with inherited heterozygous variant in AFG3L2 gene. Treatment with levodopa offered variable clinical benefits. CONCLUSION: Our report emphasizes phenotypic heterogeneity in children and adults with heterozygous variant in AFG3L2 gene.