Edit concept Question Editor Create issue ticket

Autosomal Dominant Classic Optic Atrophy

Kjer Optic Atrophy


Presentation

  • Clinical presentation can be highly variable. The visual impairment is usually moderate, but ranges from severe (legal blindness with acuity OPA1, which encodes a mitochondrial inner membrane protein. Optic atrophy can also be syndromic.[blueprintgenetics.com]
  • Individuals typically present with bilateral and slow vision loss starting in the first or second decade of life.[eyewiki.aao.org]
  • BACKGROUND OF THE PRESENT INVENTION Optic neuropathy or, often called, optic atrophy describes the loss of some or most of the fibers of the optic nerve.[google.sr]
  • However, pendular and triangular waveforms may also be present. The nystagmus may rarely be vertical.[diseaseinfosearch.org]
  • The work presented in this thesis provides further insight into the molecular and genetic basis of two classical forms of inherited optic neuropathy, namely autosomal dominant optic atrophy (DOA) and Wolfram syndrome.[ethos.bl.uk]
Rigor
  • Incorporation of rigorous quality control steps throughout the workflow of the pipeline ensures the consistency, validity and accuracy of results. Our pipeline is streamlined to maximize sensitivity without sacrificing specificity.[blueprintgenetics.com]
  • Rigorous clinical evaluation should precede diagnostic molecular testing.[aetna.com]
Movement Disorder
  • Neurologic abnormalities such as postural tremor, peripheral neuropathy, nonspecific myopathy, and movement disorders have been reported to be more common in individuals with LHON than in controls.[ncbi.nlm.nih.gov]
  • Hyperkinetic movement disorders in children. In: UpToDate Online Journal [serial online]. Waltham, MA: UpToDate; updated April 2007. Weber S, Tonshoff B.[aetna.com]
Macula
  • Histopathology shows a normal outer retina and loss of retinal ganglion cells, primarily in the macula and in the papillo-macular bundle of the optic nerve.[ncbi.nlm.nih.gov]
  • G25.0 Essential tremor [benign] G25.3 Myoclonus [dystonia] G30.0 - G30.9 Alzheimer's disease G43.401 - G43.419 Hemiplegic migraine G47.411 - G47.429 Narcolepsy and cataplexy H35.051 - H35.059 Retinal neovascularization H35.30 - H35.33 Degeneration of macula[aetna.com]
Central Scotoma
  • METHOD: Three patients with bilateral optic atrophy and central scotomas of their visual fields were clinically diagnosed with ADOA.[ncbi.nlm.nih.gov]
  • scotoma Temporal pallor and atrophy Anomalous configuration DOA110 16 0.3/0.3 -1.75/-1.25 Dyschromatopsia, no specific axis Outer borders normal, mild relative central scotoma Temporal pallor Delayed implicit times Figure 2 Pedigrees of three ADOA families[bmcmedgenet.biomedcentral.com]
  • Humphrey visual field test shows cecocentral scotoma in right eye and central scotoma in left eye.[eyewiki.aao.org]
  • Visual field testing reveals a central scotoma, a cecocentral scotoma or an enlarged blind spot. There may be extension of the scotoma to the superior temporal field in late stages. OCT shows thinning of the nerve fiber layer.[healio.com]
Impulsivity
  • Optic atrophy is a condition that affects the optic nerve, which carries impulses from the eye to the brain. Optic atrophy type 1 (OA1) is clinically characterized by progressive decrease in visual acuity from early childhood onwards.[blueprintgenetics.com]
Psychiatric Symptoms
  • Psychiatric symptoms such as personality change and paranoia may appear in childhood and progress.[ncbi.nlm.nih.gov]
Chronic Progressive External Ophthalmoplegia
  • external ophthalmoplegia and mitochondrial myopathy with cytochrome c oxidase negative and Ragged Red Fibres.[haplogroup.org]
  • CPEO: Chronic Progressive External Ophthalmoplegia Weakness of eye muscles causing droopy eyelids (ptosis) and inability to move the eyeballs Cause: Single or multiple mtDNA deletions; mtDNA point mutations (A3243G most common) DAD: Diabetes and Deafness[rarediseasesnetwork.org]
  • Dominant optic nerve atrophy with progressive hearing loss and chronic progressive external ophthalmoplegia (CPEO).[ncbi.nlm.nih.gov]
  • Some individuals display features that fall into distinct syndromes such as chronic progressive external ophthalmoplegia (CPEO), Kearns‐Sayre syndrome (KSS), Leber hereditary optic neuropathy (LHON), Leigh syndrome (LS), mitochondrial encephalomyopathy[aetna.com]
Dysarthria
  • Ophthalmoplegia, myopathy, ataxia, and neuropathy, Behr synrome, Mitochondrial DNA depletion syndrome 14 AD/AR 96 390 OPA3 Optic atrophy, 3-methylglutaconic aciduria AD/AR 13 15 POLG POLG-related ataxia neuropathy spectrum disorders, Sensory ataxia, dysarthria[blueprintgenetics.com]
  • Associated symptoms may include hearing loss, myopathy, ataxia, peripheral neuropathy, dysarthria, optic atrophy, dementia. parkinsonism, and psychiatric problems.[rarediseasesnetwork.org]
  • Familial Neonatal, 2 5 Seizures, Cortical Blindness, Microcephaly Syndrome 1 Sengers syndrome 3 Senior-Loken Syndrome 4 2 Senior-Loken Syndrome 5 5 Senior-Loken Syndrome 6 5 Senior-Loken Syndrome 7 4 Senior-Loken Syndrome 8 2 Sensory Ataxic Neuropathy, Dysarthria[preventiongenetics.com]
  • Affected individuals typically present with asymmetric focal weakness of the extremities (stumbling or poor handgrip) or bulbar findings (dysarthria, dysphagia).[aetna.com]
Confusion
  • The acquired blue-yellow loss (tritanopia) helps differentiate OPA1 from other optic neuropathies in which the axis of confusion is red-green: OPA2 (OMIM 311050 ).[ncbi.nlm.nih.gov]
  • The condition is rare, occurring in 1 in 10,000 live births. [51] This situation should not be confused with deformational unilateral skull deformity.[emedicine.medscape.com]
  • Familial cold autoinflammatory syndrome shares symptoms, and should not be confused, with acquired cold urticaria, a more common condition mediated by different mechanisms that usually develop later in life and are rarely inherited.[aetna.com]
Cognitive Deficit
  • Pathogenic truncating variants are responsible for this neuroophthalmologic syndrome consisting of early-onset bilateral optic atrophy and later-onset spasticity, extrapyramidal dysfunction, and cognitive deficit.[ncbi.nlm.nih.gov]
Personality Change
  • Psychiatric symptoms such as personality change and paranoia may appear in childhood and progress.[ncbi.nlm.nih.gov]

Workup

Central Scotoma
  • METHOD: Three patients with bilateral optic atrophy and central scotomas of their visual fields were clinically diagnosed with ADOA.[ncbi.nlm.nih.gov]
  • scotoma Temporal pallor and atrophy Anomalous configuration DOA110 16 0.3/0.3 -1.75/-1.25 Dyschromatopsia, no specific axis Outer borders normal, mild relative central scotoma Temporal pallor Delayed implicit times Figure 2 Pedigrees of three ADOA families[bmcmedgenet.biomedcentral.com]
  • Humphrey visual field test shows cecocentral scotoma in right eye and central scotoma in left eye.[eyewiki.aao.org]
  • Visual field testing reveals a central scotoma, a cecocentral scotoma or an enlarged blind spot. There may be extension of the scotoma to the superior temporal field in late stages. OCT shows thinning of the nerve fiber layer.[healio.com]

Treatment

  • State-of-the-art coverage of key areas such as OCT and all of the newest imaging techniques for the eye, orbit and visual pathways; anti-VEGF treatment for retinopathy of prematurity; and minimally invasive strabismus surgery.[books.google.com]
  • Food and Drug Administration has chosen Wave Life Sciences’ planned phase 2/3 study of suvodirsen, its lead experimental therapy for the treatment of Duchenne muscular dystrophy, to break new ground.[globalgenes.org]
  • FIG. 6 is a fluoangiography of SR prior to treatment. FIG. 7 is an optical coherence tomography scan of SR before treatment.[google.sr]
  • Acetazolamide in the treatment of X-linked retinoschisis maculopathy. Arch Ophthalmol. 2007;125:571-573. Grover S, Apushkin MA, Fishman GA. Topical dorzolamide for the treatment of cystoid macular edema in patients with retinitis pigmentosa.[rarediseases.org]
  • Most exciting of all, more sophisticated treatment methods have evolved over the past 20 years. The age at presentation determines the treatment. If possible, provide early treatment and direct it at the cranial vault.[emedicine.medscape.com]

Prognosis

  • Prognosis is variable, with moderate to severe visual loss and nystagmus. Systemic abnormalities include spastic gait, ataxia and mental handicap. 23.[slideshare.net]
  • The prognosis for Leigh syndrome is poor. Depending on the defect, individuals typically live a few years.[rarediseasesnetwork.org]
  • The presence of syndactyly seems to represent a different genetic variant of LQTS also associated with a poor prognosis.[aetna.com]
  • Patients with type I have the best long-term prognosis, whereas those with types II and III have neurologic compromise and die young. [12] Saethre-Chotzen Syndrome This is an autosomal dominant condition with full penetrance.[emedicine.medscape.com]

Etiology

  • Lyons, both globally recognized leaders, provide authoritative coverage of all the pediatric ophthalmic conditions you’re likely to encounter in practice, including the latest clinical advances in etiology, diagnosis, and medical and surgical management[books.google.com]
  • […] parasellar region. [7] Family history Autosomal dominant optic atrophy is a genetically heterogeneous condition, associated with a genetic mutation in the OPA1 on 3q28. [1] Leber’s hereditary optic neuropathy and dominant optic atrophy have mitochondrial etiology[explainmedicine.com]
  • Tobacco use increases oxidative DNA damage in sperm-possible etiology of childhood cancer. Asian Pac J Cancer Prev 2015; 16: 6967-6972. F rancis PJ. Genetics of inherited retinal disease. JRSM 2006; 99:189-191.[djo.org.in]
  • Candidates for diagnostic testing include infants, children, and adults with generalized hypotonia and proximal muscle weakness of unknown etiology.[aetna.com]
  • […] mercaptopurine 6-MP 6MP toxicity 6-thioguanine 6-TG 6TG AZA toxicity Azathioprine S-adenosyl-L-methionine genotype Thioguanine Thiopurine S-Methyltransferase genotype Thiopurine TPMT mutation TPMT gene TPMT genetics 0030133 Thrombotic Risk, Inherited Etiologies[aruplab.com]

Epidemiology

  • DOA - Optic atrophy - deafness- polyneuropathy - myopathy Classification (Orphanet): - Inborn errors of metabolism - Rare eye disease - Rare genetic disease - Rare neurologic disease Classification (ICD10): - Diseases of the ear and mastoid process - Epidemiological[csbg.cnb.csic.es]
  • Further epidemiological studies are needed in order to determine the prevalence of ADOA in Singapore.[iovs.arvojournals.org]
  • 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]
  • Epidemiology and penetrance of Leber hereditary optic neuropathy in Finland. Eur J Hum Genet 2007; 15:1079-89. S acai PY, Salomão SR, Carelli V, Pereira JM, Belfort R, Sadun AA, et al.[djo.org.in]
  • Clinical and epidemiological aspects. Acta Ophthalmol Scand. 1996, 74: 3-7. 10.1111/j.1600-0420.1996.tb00672.x.[bmcmedgenet.biomedcentral.com]
Sex distribution
Age distribution

Pathophysiology

  • This syndrome has a discrete pathophysiology and differs genetically and clinically from recessive Wolfram syndrome. Received October 25, 2016. Accepted April 21, 2017. 2017 by the American Diabetes Association.[diabetes.diabetesjournals.org]
  • The unifying pathophysiological theme is mitochondrial dysfunction, but the specific disease mechanisms that ultimately precipitate neuronal loss, particularly retinal ganglion cell (RGC) degeneration, still remain unclear.[ethos.bl.uk]
  • Hereditary optic neuropathies and a proposed common pathophysiology through mitochondrial dysfunction.[eyewiki.aao.org]
  • Clinical features, molecular genetics, and pathophysiology of dominant optic atrophy. J Med Genet. 1998;35(10):793-800. Vortruba M, Thiselton D, Bhattacharya SS. Optic disc morphology of patients with OPA1 autosomal dominant optic atrophy.[healio.com]
  • We found four different OPA1 mutations, including frameshift and missense mutations, to segregate with the disease, demonstrating a role for mitochondria in retinal ganglion cell pathophysiology [1].[wikigenes.org]

Prevention

  • Knowledge of the pathogenesis, genetics, and molecular biology of neuromuscular disorders is essential both in developing and applying new therapies and preventive measures, and in formulating genetic and prognostic advice.[books.google.com]
  • Early diagnosis and prevention of complications are the two branches of its treatment, because even though an important progression in the treatment has been done, with substances such as 4-phenylbutyric acid, there is still no curative treatment.[medigraphic.com]
  • It must be performed with care to prevent any neurologic problems. Spinal fusion should be performed, and cord pressure should be decompressed.[emedicine.medscape.com]
  • Mohr-Tranebjaerg syndrome XLR 3 TMEM126A 612988 Optic Atrophy 7 AR 0 WFS1 606201 noninsulin-dependent diabetes mellitus / Diabetes mellitus type II; Wolfram syndrome; Deafness, autosomal dominant 6/14/38; Wolfram-like syndrome AD, AR 17 To date, there is no preventative[centogene.com]
  • DESCRIPTION OF THE PREFERRED EMBODIMENTS As used herein, the term “ophthalmic neuroprotector” means a ophthalmic composition that can be used in therapy that prevents, retards or reverses apoptosis associated neuronal death resulting from primary neuronal[google.sr]

Ask Question

5000 Characters left Format the text using: # Heading, **bold**, _italic_. HTML code is not allowed.
By publishing this question you agree to the TOS and Privacy policy.
• Use a precise title for your question.
• Ask a specific question and provide age, sex, symptoms, type and duration of treatment.
• Respect your own and other people's privacy, never post full names or contact information.
• Inappropriate questions will be deleted.
• In urgent cases contact a physician, visit a hospital or call an emergency service!