OPA1 gene

• Overview
• Dominant optic atrophy
• References

Overview

Gene (OMIM No.)	OPA1 (#605290)
Function of gene/protein	Protein: mitochondrial dynamin like GTPase Inner mitochondrial membrane protein regulating mitochondrial stability and energy output Pathogenic mutations result in mitochondrial dysfunction and preferential degeneration of retinal ganglion cells (RGCs)
Clinical phenotype (OMIM phenotype no.)	Optic atrophy 1 (#165500) Optic atrophy plus syndrome (#125250) Behr syndrome (#210000)
Inheritance	Autosomal dominant (majority) and autosomal recessive Heterozygous OPA1 mutations are associated with isolated dominant optic atrophy (~75% of cases) or syndromic optic atrophy (dominant optic atrophy plus syndrome) Compound heterozygous OPA1 mutations are associated with Behr syndrome
Ocular features	Variable phenotypic severity (even within families); usually more severe visual impairment in syndromic forms Symptom onset usually in the first two decades of life Bilateral progressive, painless visual loss without spontaneous recovery and central/centrocaecal scotoma Dyschromatopsia Temporal optic nerve head pallor (preferential degeneration of RGCs of the papillomacular bundle) Chronic progressive external ophthalmoplegia has been reported in syndromic forms
Systemic features	Sensorineural hearing loss (most common) Proximal myopathy Peripheral neuropathy Ataxia Spasticity Multiple sclerosis-like illness Behr syndrome (ataxia, spasticity and peripheral neuropathy in addition to early onset progressive optic neuropathy)
Key investigations	Orthoptic assessment and refraction Colour vision testing Perimetry: central/centrocaecal scotoma Optic nerve head photograph OCT of the optic disc: Global thinning of the peripapillary retinal nerve fibre layer (nasal aspect is often relatively spared) Electrophysiology MRI brain Audiology Systemic assessment with a pediatricians, neurologists and other relevant specialists to exclude other causes of optic neuropathies
Molecular diagnosis	Next generation sequencing Targeted gene panels (optic atrophy) Whole exome sequencing Whole genome sequencing
Management	Ocular Supportive management Smoking cessation Avoid excessive alcohol consumption Systemic Multidisciplinary approach coordinated by paediatrician and/or neurologist Hearing aids/cochlear implants helpful in those with sensorineural hearing loss Involvement of physiotherapists and occupational therapists to address motor disability Early involvement of practitioners familiar with developmental surveillance and intervention for children with visual impairment
Therapies under research	Idebenone treatment associated with visual stabilisation and recovery in a retrospective cohort study
Further information	Medline Plus

Jump to top

---

References

Jump to top