# The Neuro-Ophthalmologic Manifestations of SPG7-Associated Disease

## TL;DR

This review explores the eye-related neurological symptoms caused by SPG7 gene mutations and highlights the importance of recognizing these signs in clinical practice.

## Contribution

The paper provides a detailed overview of the diverse neuro-ophthalmologic features associated with SPG7 mutations.

## Key findings

- SPG7 mutations are linked to optic atrophy, nystagmus, and progressive external ophthalmoplegia.
- Mitochondrial dysfunction plays a central role in the pathophysiology of SPG7-associated neuro-ophthalmologic features.
- SPG7 should be considered in the differential diagnosis of optic atrophy and cerebellar eye signs.

## Abstract

The gene SPG7 codes for the protein paraplegin, a subunit of the m-AAA protease in the inner mitochondrial membrane involved in protein quality control. SPG7 was initially identified as causing autosomal recessive hereditary spastic paraplegia (HSP), with a pure (insidiously progressive bilateral leg weakness and spasticity) and complex (with additional neurologic features including cerebellar signs and optic atrophy) forms. Now identified as one of the most common causes of HSP, SPG7-associated disease has been linked to additional neuro-ophthalmologic features, including isolated dominant optic atrophy, cerebellar eye signs (various forms of nystagmus, dysmetric saccades), progressive external ophthalmoplegia (PEO), and supranuclear vertical palsy. This review describes in detail the various neuro-ophthalmologic presentations of SPG7-associated disease, illustrating the role of mitochondrial dysfunction in the pathophysiology of these different entities. Knowledge of the different manifestations of SPG7-associated disease is crucial for both neurologists and ophthalmologists, and SPG7 should be considered in the work-up of patients presenting with entities such as optic atrophy, PEO, and cerebellar eye signs.