Homozygous FDXR variant in twin sisters with spastic paraparesis followed by acute progressive flaccid quadriparesis.

backgroundFDXR-related disorders (FRDs) are rare mitochondrial conditions typically presenting with progressive optic atrophy and neuropathy. We report identical twins presenting with acute-onset flaccid quadriparesis following a respiratory infection, expanding the known phenotypic spectrum of FDXR variants. CASE PRESENTATION: 22-year-old monozygotic twins from a consanguineous Iranian family developed progressive weakness after an upper respiratory infection, initially diagnosed as Guillain-Barré syndrome. Despite IVIG and plasmapheresis, both progressed to flaccid quadriplegia. Twin A. had additional manifestations including blindness, dysarthria, and incontinence, that were not present in Twin B. Extensive workup excluded inflammatory, infectious, and some metabolic etiologies. Whole exome sequencing (WES) revealed a homozygous FDXR missense variant (c.463C>T, p.Arg155Trp) in Twin A.

conclusionsThis represents the first report of the mentioned FDXR variant in monozygotic twins. The twins' phenotypic discordance despite genetic identity suggests environmental or epigenetic modifiers. Our findings underscore: 1. FDXR variants should be considered in acute neuropathies unresponsive to immunotherapy. 2. The c.463C>T variant may cause both acute and chronic presentations.