Optic Atrophy and Generalized Chorea in a Patient Harboring an OPA10/RTN4IP1 Pathogenic Variant

Abstract

Abstract RTN4IP1 pathogenic variants (OPA10 syndrome) have been described in patients with early-onset recessive optic neuropathy and recently associated with a broader clinical spectrum, from isolated optic neuropathy to severe encephalopathies with epilepsy. Here we present a case of a patient with a complex clinical picture characterized by bilateral optic nerve atrophy, horizontal nystagmus, myopia, mild intellectual disability, generalized chorea, isolated small subependymal heterotopia, and asynchronous self-resolving midbrain MRI (magnetic resonance imaging) lesions. By using massive gene sequencing, we identified in this patient the c.308G > A (p.Arg103His) homozygous pathogenic variant in the RTN4IP1 gene. Complex movement disorders and relapsing-remitting neuroradiological lesions have not been previously reported in this condition. Our case expands the clinical spectrum of OPA10 syndrome and opens new opportunities for the molecular diagnosis.