Accumulation of complex I assembly intermediates in a novel presentation of RTN4IP1-related disorder with developmental delay, ataxia and dyskinesia.

BACKGROUND

Biallelic variants in RTN4IP1 (OPA10) are associated with a wide phenotypic spectrum including optic atrophy with or without ataxia, impaired intellectual development and seizures (OMIM 616732). Brain imaging ranges from normal to white matter changes and cerebral atrophy. Earlier literature has reported a combined complex I and IV deficiency in RTN4IP1 cases.

RESULTS

We report on three siblings, compound heterozygous for novel RTN4IP1 variants who presented with a movement disorder with pronounced dyskinesia along with developmental delay, optic atrophy and ataxia. Furthermore, atypical brain MRI findings with symmetrical bilateral substantia nigra abnormalities were observed in two of them. Blue native polyacrylamide gel electrophoresis performed on fibroblasts of two patients revealed a defect in the complex I assembly process.

CONCLUSION

Thus, we expand the clinical spectrum of RTN4IP1-associated disease with movement disorder, substantia nigra abnormalities and complex I assembly defects.