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Autosomal Dominant Optic Atrophy

DOA


Presentation

  • MATERIALS AND METHODS: The proband, a 10-year-old boy, presented with progressive visual failure.[ncbi.nlm.nih.gov]
  • A large four-generation Chinese family with autosomal dominant optic atrophy (ADOA) was investigated in the present study. Eight of the family members were affected in this pedigree.[ncbi.nlm.nih.gov]
  • Other signs were present in some patients such as decreased color discrimination and a gray crescent within the neuroretinal rim.[ncbi.nlm.nih.gov]
  • The recurrent c.2708_2711delTTAG mutation was found in 2 patients with a severe congenital presentation of the disease.[ncbi.nlm.nih.gov]
  • CONCLUSION: The present study demonstrates that a mutation in the OPA1 gene can cause optic atrophy in Chinese patients, and supports the notion that OPA1 mutation may lead to OPA1 combined with hearing loss.[ncbi.nlm.nih.gov]
Hearing Impairment
  • We identified one novel WFS1 missense mutation E864K, c.2590G-- A in exon 8 that co-segregates with ADOA combined with hearing impairment and impaired glucose regulation.[ncbi.nlm.nih.gov]
  • The hearing impairment phenotype is a progressive auditory neuropathy, while the neurologic, visual, and neuropsychiatric signs vary in degree of severity and rate of progression. Females may have mild hearing impairment and focal dystonia.[ncbi.nlm.nih.gov]
  • In about 10–20% of ADOA cases a more severe ADOA “plus” phenotype (DOA ; OMIM: # 125250) with extra-ophthalmic manifestation e.g. sensorineural hearing impairment and neuromuscular symptoms has been reported [ 6 – 8 ].[journals.plos.org]
  • Identification of p.A684V missense mutation in the WFS1 gene as a frequent cause of autosomal dominant optic atrophy and hearing impairment.[ncbi.nlm.nih.gov]
Progressive Hearing Loss
  • PURPOSE: To describe the clinical features, mode of inheritance, and linkage analysis of ten affected members of a three-generation family with progressive optic atrophy and progressive hearing loss.[ncbi.nlm.nih.gov]
  • Dominant optic nerve atrophy with progressive hearing loss and chronic progressive external ophthalmoplegia (CPEO).[ncbi.nlm.nih.gov]
Central Scotoma
  • Early loss of inferior temporal RNFL in ADOA is related to superotemporal central scotoma.[ncbi.nlm.nih.gov]
  • Humphrey visual field test shows cecocentral scotoma in right eye and central scotoma in left eye.[eyewiki.org]
  • Goldmann visual field examination revealed bilateral central scotoma, and slit-lamp examination showed bilateral cerulean cataract. Electroretinography was normal and visual-evoked potentials showed bilateral optic nerve dysfunction.[karger.com]
  • Leber's hereditary optic neuropathy Dominant optic atrophy Optic neuropathy Color vision defect Tritan color vision defect Blue-yellow color vision defect Central scotoma Maternal inheritance Mitochondrial inheritance Mutation DNA Mitochondria.[journals.lww.com]
Visual Acuity Decreased
  • Visual acuity decreased with decreasing GC-IPL thickness (p 0.0006 in c.983A G and p 0.0084 in c.2708_2711delTTAG).[ncbi.nlm.nih.gov]
  • It is a childhood onset disorder typically characterized by a progressive loss in central vision, color vision deficits (dyschromatopsia), decreased visual acuity, decreased sensitivity of the central retinal field (paracentral scotomas), and asymmetric[egl-eurofins.com]

Workup

  • Clinical Presentation of LHON/DOA and Clinical Workup Leber’s hereditary optic neuropathy typically affects young adult males presenting with unilateral or bilateral subacute/acute painless loss of central vision.[doi.org]
Central Scotoma
  • Early loss of inferior temporal RNFL in ADOA is related to superotemporal central scotoma.[ncbi.nlm.nih.gov]
  • Humphrey visual field test shows cecocentral scotoma in right eye and central scotoma in left eye.[eyewiki.org]
  • Goldmann visual field examination revealed bilateral central scotoma, and slit-lamp examination showed bilateral cerulean cataract. Electroretinography was normal and visual-evoked potentials showed bilateral optic nerve dysfunction.[karger.com]
  • Leber's hereditary optic neuropathy Dominant optic atrophy Optic neuropathy Color vision defect Tritan color vision defect Blue-yellow color vision defect Central scotoma Maternal inheritance Mitochondrial inheritance Mutation DNA Mitochondria.[journals.lww.com]

Treatment

  • We showed an increased percentage of apoptotic cells in ADOA patients compared to controls, both in basal culture conditions and after 2-deoxy-D-ribose treatment.[ncbi.nlm.nih.gov]
  • You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.[rarediseases.info.nih.gov]
  • Treatment of acute hyperkalaemia in adults [PDF] This guideline has been developed to improve the treatment of acute hyperkalaemia and reduce the risk of complications associated with hyperkalaemia and its treatment. This guideline is a...[evidence.nhs.uk]
  • Currently, there is no effective treatment for this group of diseases. However, stem cell therapy holds great potential for replacing lost RGCs of patients.[ncbi.nlm.nih.gov]
  • Coverage includes major updates on genetics of diseases, new diagnostic techniques, and the newest treatment options.[books.google.de]

Prognosis

  • Visual prognosis is relatively good in Kjer's dominant optic atrophy with stable or slow progression of visual loss.[ncbi.nlm.nih.gov]
  • This genotype-phenotype heterogeneity may explain why some patients have progressive visual loss while others have a relatively stable prognosis. 2015 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.[ncbi.nlm.nih.gov]
  • Prognosis Vision seems to be more severely affected in patients with ADOA plus than in patients with no extra ocular involvement. If associated, hearing loss can further impair social communication.[orpha.net]
  • Optic atrophy secondary to vascular, traumatic, degenerative, and some toxic causes has a negative prognosis.[tsbvi.edu]
  • Prognosis Visual impairment in ADOA is classically irreversible, and spontaneous recovery has been only exceptionally reported. Visual loss is usually mild, but can at times worsen later during lifetime.[orpha.net]

Etiology

  • They are organised into groups, and further divided into clinical, etiological or histopathological sub-types.[orpha.net]
  • Etiology ADOA plus is caused by mutations in the OPA1 gene (3q29), encoding a dynamin-like GTPase involved in the fusion of the inner mitochondrial membrane.[orpha.net]
  • Etiology A majority, but not all ADOA patients harbor mutations in the gene OPA1 (3q29) which codes for an inner mitochondrial membrane protein intricately involved in mitochondrial biogenesis, mitochondrial DNA replication and network stability.[orpha.net]

Epidemiology

  • Further epidemiological studies are needed in order to determine the prevalence of ADOA in South-East Asia.[ncbi.nlm.nih.gov]
  • Clinical and epidemiological aspects. Acta Ophthalmol Scand. 1996;74(1):3-7. Votruba M, Fitzke FW, Holder CE, Carter A, Bhattacharya SS, Moore AT. Clinical features in affected individuals from 21 pedigrees with dominant optic atrophy.[eyewiki.aao.org]
  • Clinical and epidemiological aspects. Acta Ophthalmol Scand. 1996;74(1):3-7. 2. Votruba M, Fitzke FW, Holder CE, Carter A, Bhattacharya SS, Moore AT. Clinical features in affected individuals from 21 pedigrees with dominant optic atrophy.[eyewiki.org]
  • Further epidemiological studies are needed in order to determine the prevalence of ADOA in Singapore.[iovs.arvojournals.org]
  • Summary Epidemiology Autosomal dominant optic atrophy plus syndrome (ADOA plus) accounts for approximately 20% of all ADOA cases.[orpha.net]
Sex distribution
Age distribution

Pathophysiology

  • CONCLUSION: We conclude that the pathophysiology of ADOA likely stems from the role of OPA1 in mitochondrial structure or fusion and not from OPA1 support of oxidative phosphorylation.[ncbi.nlm.nih.gov]
  • Further genome-wide linkage analysis and identification of the disease-associated gene will help define the pathophysiology of this syndrome.[ncbi.nlm.nih.gov]
  • Evaluation of the mutation spectrum indicates more than one pathophysiological mechanism for adOA. Preliminary data suggests that phenotype-genotype correlation is complex, implying a role for other genetic modifying or environmental factors.[ncbi.nlm.nih.gov]
  • Concluding, we could confirm that oxidative stress-induced apoptosis may play a key role in the pathophysiological process bringing to retinal ganglion cells degeneration in ADOA. Copyright 2015. Published by Elsevier B.V.[ncbi.nlm.nih.gov]
  • Hereditary optic neuropathies and a proposed common pathophysiology through mitochondrial dysfunction.[eyewiki.org]

Prevention

  • Identification of genetic variants that enable this response may provide novel therapeutic insights into OXPHOS compensation for preventing vision loss in optic neuropathies.[ncbi.nlm.nih.gov]
  • The expertise and facilities of the combined site of IoO and Moorfields Eye Hospital (MEH) offers a unique environment in which to pursue eye research and to make advances in the prevention and treatment of disease.[findaphd.com]
  • There is currently no way to prevent or cure DOA, but affected people may benefit from low vision aids. [2] Last updated: 12/27/2015 Dominant optic atrophy (DOA) is inherited in an autosomal dominant manner.[rarediseases.info.nih.gov]
  • Optimized allotopic expression of the human mitochondrial ND4 prevents blindness in a rat model of mitochondrial dysfunction.[ncbi.nlm.nih.gov]
  • Downregulation of apoptosis-inducing factor in Harlequin mice induces progressive and severe optic atrophy which is durably prevented by AAV2-AIF1 gene therapy.[doi.org]

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