Presentation
MATERIALS AND METHODS: The proband, a 10-year-old boy, presented with progressive visual failure. [ncbi.nlm.nih.gov]
Individuals typically present with bilateral and slow vision loss starting in the first or second decade of life. [eyewiki.aao.org]
Musculoskeletal
- Myalgia
In a young patient, previous history of eye pain, paraesthesiae, ataxia or weakness suggest demyelination In an older patient, previous history of transient visual loss, diplopia, temporal pain, jaw claudication, fatigue, weight loss and myalgia suggests [patient.info]
Ears
- 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]
Neither the maternal grandparents nor the uncle of the proband had hearing impairment. All affected individuals had no symptoms additional to progressive sensorineural hearing impairment and optic atrophy. [molvis.org]
Showing of 28 | 80%-99% of people have these symptoms Impaired pain sensation Decreased pain sensation 0007328 Optic atrophy 0000648 Sensorineural hearing impairment 0000407 30%-79% of people have these symptoms Color vision defect Abnormal color vision [rarediseases.info.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]
Eyes
- Central Scotoma
Early loss of inferior temporal RNFL in ADOA is related to superotemporal central scotoma. [ncbi.nlm.nih.gov]
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]
Central-seco scotomas were evident in both eyes, with the loss extending into both foveas. [healio.com]
Humphrey visual field test shows cecocentral scotoma in right eye and central scotoma in left eye. [eyewiki.aao.org]
- 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]
acuity Decreased clarity of vision 0007663 Tritanomaly Blue yellow color blindness 0000552 Showing of 28 | Last updated: 6/1/2019 Autosomal dominant optic atrophy plus syndrome (ADOA plus) is caused by mutations (changes) in the OPA1 gene. [rarediseases.info.nih.gov]
Patient V.1, a female born in 1967, first had a decrease in visual acuity at the age of 12. At age 18, visual acuity was 4/10 in each eye. [jmg.bmj.com]
- Progressive Loss of Vision
Ophthalmological signs of this 38-year-old woman consisted of (1) bilateral optic atrophy and nystagmus since the first year of life, (2) progressive loss of vision, and (3) bilateral cerulean cataract at age 37. [karger.com]
Bilateral, slowly progressive loss of vision; OPA1 gene on chromosome 3q28 ( 2 ) Autosomal recessive optic atrophy: OPA6 gene, rare ( 2 ) Optic atrophies associated with complex genetic disorders: Disorders of amino acid metabolism Hyperhomocysteinemia [unboundmedicine.com]
This may progress later in life, resulting in more severe loss of visual acuity. TREATMENT There is currently no way to reverse the vision loss associated with dominant optic atrophy. [webeye.ophth.uiowa.edu]
There is incomplete penetrance and the classical clinical picture of DOA differs from LHON in that the former presents as a slowly progressive loss of vision with a smaller central or cecocentral scotoma ( 51 ). [doi.org]
Neurologic
- Cerebellar Ataxia
Clinical examination at the age of 38 showed cerebellar ataxia, lower limb areflexia, pinprick and light-touch hypoesthesia, and pes cavus. Ophthalmological examination showed a visual acuity of 1/10 in both eyes. [karger.com]
ataxia, spastic paraparesis and myopathy. [umdf.org]
(cerebellar syndrome with retinal degeneration), and ADCA III (pure cerebellar syndrome). [elsevier.es]
Furthermore, pathogenic variants causing OPA with cerebellar ataxia, high myopia, spastic paraplegia, or other extra-ocular findings have been reported 7. [centogene.com]
In complicated cases of autosomal dominant optic atrophy, in addition to bilateral optic neuropathy, several other neurological signs of neurological involvement can be observed: peripheral neuropathy, deafness, cerebellar ataxia, spastic paraparesis, [en.wikipedia.org]
- Chronic Progressive External Ophthalmoplegia
From the third decade onwards, other extra-ocular manifestations may appear, such as chronic progressive external ophthalmoplegia, proximal myopathy, ataxia and axonal sensory motor polyneuropathy. [orpha.net]
Dominant optic nerve atrophy with progressive hearing loss and chronic progressive external ophthalmoplegia (CPEO). [ncbi.nlm.nih.gov]
- Tingling
Other symptoms of ADOA plus may develop in adulthood and include muscle weakness ( myopathy ), weakness of the eye muscles ( ophthalmoplegia ), trouble coordinating movements ( ataxia ), and pain and tingling in the arms and legs ( peripheral neuropathy [rarediseases.info.nih.gov]
- Paresthesia
Additional symptoms consisted of intractable constipation alternating with severe diarrhea since childhood, together with gait unsteadiness, paresthesias in the four extremities, cramps, and burning pain in the lower limbs since the age of 35. [karger.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]
Visual Field Test
- Central Scotoma
Early loss of inferior temporal RNFL in ADOA is related to superotemporal central scotoma. [ncbi.nlm.nih.gov]
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]
Central-seco scotomas were evident in both eyes, with the loss extending into both foveas. [healio.com]
Humphrey visual field test shows cecocentral scotoma in right eye and central scotoma in left eye. [eyewiki.aao.org]
Treatment
It provides molecular insights for clinical genetic diagnosis and treatment of optic atrophy. Publication type, MeSH terms, Substances Publication type Research Support, Non-U.S. [ncbi.nlm.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]
Treatment options include visual and hearing aids. [rarediseases.info.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]
It addresses diagnosis, pathophysiology, management and prognosis and is written in a clear, concise style for quick, easy reference in the clinic. [books.google.de]
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]
Etiology
Etiology and Pathophysiology Genetic etiologies usually involve defects in mitochondrial function. Exposure of retinal nerve cells to light normally results in the generation of free radical species. [unboundmedicine.com]
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]
In addition, there was nothing in the history that suggested a toxic etiology. Genetic testing Molecular genetic testing can be helpful in diagnosing autosomal dominant optic atrophy. [healio.com]
Epidemiology
Further epidemiological studies are needed in order to determine the prevalence of ADOA in South-East Asia. [ncbi.nlm.nih.gov]
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]
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]
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]
It addresses diagnosis, pathophysiology, management and prognosis and is written in a clear, concise style for quick, easy reference in the clinic. [books.google.de]
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]
Prevention People noticing a decrease in vision (central and/or side vision) should ask their eye care practitioner for a check up. Patients should also go for regular vision exams. [medical-dictionary.thefreedictionary.com]
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]
Contact Us Venue Hire Job vacancies About Us Our vision is that everyone has access to and receives high quality eye care for the prevention and treatment of eye disease in order to optimise, preserve and restore vision. [rcophth.ac.uk]
A., PEARCE-KELLING S., LI Z., et al. (2009) - Steroids do not prevent photoreceptor degeneration in the light-exposed T4R rhodopsin mutant dog retina irrespective of AP-1 inhibition. Invest. Ophthalmol. Vis. Sci. 50, 3482–3494. IWABE S., YING G. [genodog.fr]