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Classic Autosomal Dominant Optic Atrophy

Optic Atrophy Type 1


Presentation

  • Individuals typically present with bilateral and slow vision loss starting in the first or second decade of life.[eyewiki.aao.org]
  • Strabismus and ptosis are often present. There may also be retinal hypopigmentation. Cataract, glaucoma, and corneal opacities are not present.[disorders.eyes.arizona.edu]
  • 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]
  • Besides the common symptoms described above for Leigh syndrome, retinitis pigmentosa is often present and an important diagnostic clue.[rarediseasesnetwork.org]
Italian
  • Medical Subject Headings Italian D029241 L2137654 preferred S2475876 Y Atrofia ottica autosomica dominante Italian Medical Subject Headings Italian D029241 L6959191 no S8098549 Y Atrofia ottica dominante Italian Medical Subject Headings Italian D029241[doctor.am]
  • […] amyloidosis, Arctic type Hereditary cerebral hemorrhage with amyloidosis, Dutch type Hereditary cerebral hemorrhage with amyloidosis, Flemish type Hereditary cerebral hemorrhage with amyloidosis, Iowa type Hereditary cerebral hemorrhage with amyloidosis, Italian[csbg.cnb.csic.es]
  • Another OPA locus for autosomal dominant optic atrophy (OPA8) was mapped to 16q21-q22 in one Italian family with extraophthalmologic features extending to the auditory system [ Carelli et al 2007 ].[ncbi.nlm.nih.gov]
  • Funding This work was supported by the Telethon Grants GGP15041, GGP13222 and GGP14187; the Italian Ministry of Health (GR2010–2316392 and RC2016), the Pierfranco and Luisa Mariani Foundation, Fondazione CARIPARO, and Bulgari.[link.springer.com]
  • View Article PubMed Google Scholar Paracchini V, Seia M, Coviello D, Porcaro L, Costantino L, Capasso P, Degiorgio D, Padoan R, Corbetta C, Claut L, et al: Molecular and clinical features associated with CFTR gene rearrangements in Italian population:[bmcmedgenet.biomedcentral.com]
Movement Disorder
  • Notes Acknowledgements We acknowledge the “Cell Lines and DNA Bank of Movement Disorders and Neurodegenerative Diseases” of the Telethon Network of Genetic Biobanks (grant GTB12001J) and the Eurobiobank Network for providing patients’ samples.[link.springer.com]
  • 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]
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]
  • Color vision is variably defective and central scotomas are present.[disorders.eyes.arizona.edu]
Blurred Vision
  • The cataracts are congenital in males but apparently develop later in females who complain of blurred vision from early childhood or during teenage years.[disorders.eyes.arizona.edu]
  • Methods Patient history A 62-year-old Caucasian woman consulted for blurred vision. On examination, she was found to have a central scotoma in the right eye; visual failure occurred rapidly a few days later.[molvis.org]
Macula
  • Optical coherence tomography of the macula and electroretinogram were normal; the visual evoked potential was unrecordable in both eyes.[ijo.in]
  • Coloboma of macula-brachydactyly type B syndrome Colobomatous and areolar dystrophy Cone dystrophy with supernormal rod response Cone rod dystrophy Congenital ectropion uveae Congenital glaucoma Congenital microcoria Congenital stationary night blindness[se-atlas.de]
  • In addition, KSS patients manifest an atypical pigmentary retinopathy in which the macula is often the first part of the retina to be affected followed by the retina periphery. In some patients, all parts of the retina are affected simultaneously.[entokey.com]
  • 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]
  • AR except Fabry’s, lysozomal enzyme defects • accumulation of sphingolipids in retinal ganglion cells and macula has highest concentration (cherry red spot) With cherry red spot (Sphingolipidoses) - Tay-Sachs – most common, hexosaminodase A def, MR –[brainscape.com]
Psychiatric Symptoms
  • Psychiatric symptoms such as personality change and paranoia may appear in childhood and progress.[ncbi.nlm.nih.gov]
Dystonia
  • […] of mixed type 2 Primary Dystonia; DYT6 type ORPHA98806 G24.1 602629 Idiopathic torsion dystonia of mixed type 1 Primary Dystonia; DYT6 type ORPHA98806 G24.1 602629 Dystonia 16 2 Protein kinase, interferon-inducible double stranded RNA dependent activator[catalogue.rd-connect.eu]
  • Malformations Ceroid Lipofuscinoses Charcot Marie Tooth Chromosomal Instability Syndromes Coenzyme Q10 Deficiency Congenital Central Hypoventilation syndrome Congenital Myopathy Dementia Disorders of Folate Metabolism and Transport Distal Hereditary Myopathy Dystonia[preventiongenetics.com]
  • Dysarthria, dystonia, rigidity and corticospinal signs are often present early as well. Swallowing difficulties may be severe sometimes leading to malnutrition.[disorders.eyes.arizona.edu]
  • Deafness-dystonia-optic neuronopathy syndrome (DDON).[ncbi.nlm.nih.gov]
  • LHON-Plus: Leber Hereditary Optic Neuropathy Plus Leber hereditary optic neuropathy Plus (LHON-Plus) presents as blindness, cardiac pre-excitation syndrome, plus additional clinical manifestations such as dystonia, ataxia, myoclonus, olivopontocerebellar[rarediseasesnetwork.org]
Confusion
  • NBIA2B has a later onset (4-5 years) and profound sensorimotor impairment but there are many overlapping features and the nosology is confusing.[disorders.eyes.arizona.edu]
  • 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]
  • These characteristics are consistent with a diagnosis of Blau syndrome which is also called Jabs syndrome or familial juvenile systemic granulomatosis.1 This uncommon disorder is most often confused with juvenile idiopathic (rheumatoid) arthritis and[brainscape.com]
  • Color-axis confusion lines were not specific because of many mistakes due to low visual acuity.[molvis.org]
Tremor
  • Many have a hand tremor, some degree of hypotonia, and learning difficulties. MRI imaging often shows cerebellar and sometimes cerebral hypoplasia.[disorders.eyes.arizona.edu]
  • 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]
Personality Change
  • Psychiatric symptoms such as personality change and paranoia may appear in childhood and progress.[ncbi.nlm.nih.gov]
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]

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]
  • Color vision is variably defective and central scotomas are present.[disorders.eyes.arizona.edu]

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]
  • Treatment Treatment Options: No treatment has been reported.[disorders.eyes.arizona.edu]
  • FIG. 6 is a fluoangiography of SR prior to treatment. FIG. 7 is an optical coherence tomography scan of SR before treatment.[google.sr]
  • Treatment: As with all mitochondrial diseases, there is no cure for complex I deficiency. A variety of treatments, which may or may not be effective, include: riboflavin, thiamine, biotin, CoQ10, and carnitine.[rarediseasesnetwork.org]
  • If treatment is delayed, the injury may be irreversible. The course of treatment varies with the congenital forms of these neuropathies. There are some drug treatments that have shown modest success, such as Idebenone used to treat LOHN.[en.wikipedia.org]

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]
  • Visual prognosis in autosomal dominant optic atrophy (Kjer type). Am J Ophthalmol 1993;115:360-7. 5. Kline LB, Glaser JS. Dominant optic atrophy. The clinical profile. Arch Ophthalmol 1979;97:1680-6. [ PUBMED ] 6.[ijo.in]
  • The prognosis is uniformly terrible with most children dying before the age of 5 years.[brainscape.com]
  • Notably, age of onset, clinical symptoms, and prognosis are similar in Leigh syndrome patients with mtDNA or nuclear DNA mutations ( 80 ).[entokey.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]
  • They are organised into groups, and further divided into clinical, etiological or histopathological sub-types.[orpha.net]
  • We have successfully used this approach to identify two novel etiological genes for syndromic neonatal diabetes in our cohort ( 2 , 3 ).[diabetes.diabetesjournals.org]
  • […] 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]

Epidemiology

  • Ophthalmic Epidemiology . 14. 2007 The optic nerve head in Myocilin glaucoma. .[findanexpert.unimelb.edu.au]
  • 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]
  • 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]
  • "The Epidemiology of Leber Hereditary Optic Neuropathy in the North East of England" . The American Journal of Human Genetics . 72 (2): 333–9. doi : 10.1086/346066 . PMC 379226 . PMID 12518276 .[en.wikipedia.org]
  • 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

  • Hereditary optic neuropathies and a proposed common pathophysiology through mitochondrial dysfunction.[eyewiki.aao.org]
  • Two key features may be helpful in distinguishing acquired from inherited optic neuropathies: absence of a family history and simultaneous involvement of both eyes; the former more commonly characterized by these two features. [3] Pathophysiology [ edit[en.wikipedia.org]
  • OPA1-associated disorders: Phenotypes and pathophysiology. Int J Biochem Cell Biol 2009;41:1855-65. 2. Delettre C, Lenaers G, Pelloquin L, Belenguer P, Hamel CP. OPA1 (Kjer type) dominant optic atrophy: A novel mitochondrial disease.[ijo.in]
  • This syndrome has a discrete pathophysiology and differs genetically and clinically from recessive Wolfram syndrome. Introduction Neonatal diabetes is diagnosed before 6 months of age and reflects a severe reduction in β-cell number or function.[diabetes.diabetesjournals.org]
  • 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

  • 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]
  • Ophthalmic Epidemiology . 18. 2011 Telemedicine model to prevent blindness from familial glaucoma .[findanexpert.unimelb.edu.au]
  • Management No established treatments are available at the present time to prevent vision loss, arrest the progression of vision loss, or restore vision.[entokey.com]
  • This buffer was supplemented with 2 mM iodoacetate and 2 mM EDTA so as to prevent glycolytic ATP synthesis and ATP hydrolysis by cellular ATPases.[molvis.org]

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