Klinische FragestellungOptikus-Atrophie, hereditäre; Differentialdiagnose

NGS +

[Sanger]

Optikus-Atrophie bzw. Optikus-Neuropathie ist das Endstadium eines Krankheitsprozesses, der den retinogenen Teil der Sehbahn durch neurovaskuläre Degeneration betrifft. Auch die hereditären Optikus-Neuropathien sind durch Degeneration der retinalen Ganglienzellen gekennzeichnet, was zur bilateralen Optikus-Atrophie und fortschreitendem Verlust der Sehschärfe führt. Zusätzlich leiden diese Patienten häufig an gestörten Farbsehen. Die häufigsten Formen hereditärer Optikus-Neuropathien sind die dominante Optikus-Atrophie und die Leber hereditäre Optikus-Neuropathie. Bei beiden Erkrankungen ist die neuronale und axonale Energieversorgung durch die Mitochondrien betroffen. Optikus-Atrophie kann in jedem Lebensalter eintreten, alle klassischen Erbgänge sind vertreten. Die DNA-diagnostische Ausbeute erreicht ca. 20%. Unauffällige molekulargenetische Befunde bedeuten daher keinen Ausschluss der ophthalmologischen Verdachtsdiagnose.

Referenz: https://www.ncbi.nlm.nih.gov/books/NBK1248/

• Sympt.: Color vision deficits + centrocecal scotoma of variable density
• Sympt.: Visual impairment in early childhood, loss of visual acuity, temporal optic disc pallor
• Alias: Lebersche hereditäre Optikusatrophie (LHON)
• Alias: Optic atrophy
• Alias: Optic neuropathy
• Allelic: 3-methylglutaconic aciduria, type III (OPA3)
• Allelic: Cataract 41 (WFS1)
• Allelic: Charcot-Marie-Tooth disease, axonal, types 2A2A + 2A2B (MFN2)
• Allelic: Deafness, AD 6, 14, 38
• Allelic: Diabetes mellitus, noninsulin-dependent, association with (WFS1)
• Allelic: Encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1 (DNM1L)
• Allelic: Epileptic encephalopathy, early infantile, 48 (AP3B2)
• Allelic: Glaucoma, normal tension, susceptibility to (OPA1)
• Allelic: Hemolytic anemia due to hexokinase deficiency (HK1)
• Allelic: Hereditary motor + sensory neuropathy, Okinawa type (TFG)
• Allelic: Mitochondrial AR ataxia syndrome, includes SANDO + SCAE (POLG)
• Allelic: Mitochondrial DNA depletion syndrome 14, encephalocardiomyopathic type (OPA1)
• Allelic: Mitochondrial DNA depletion syndrome 4A, Alpers + 4B, MNGIE type (POLG)
• Allelic: Progressive external ophthalmoplegia, AR 1
• Allelic: Retinitis pigmentosa 79 (HK1)
• Allelic: Spastic ataxia 5, AR (AFG3L2)
• Allelic: Spastic paraplegia 55, AR (C12orf65)
• Allelic: Spinocerebellar ataxia 28 (AFG3L2)
• Arts syndrome (PRPS1)
• Auditory neuropathy + optic atrophy (FDXR)
• Behr syndrome (OPA1)
• Bosch-Boonstra-Schaaf optic atrophy syndrome (NR2F1)
• Brown-Vialetto-Van Laere syndrome 2 (SLC52A2)
• Coenzyme Q10 deficiency, primary, 2 (PDSS1)
• Combined oxidative phosphorylation deficiency 7 (C12orf65)
• Dystonia, childhood-onset, with optic atrophy + basal ganglia abnormalities (MECR)
• Encephalopathy due to defective mitochondrial + peroxisomal fission 2 (MFF)
• Friedreich ataxia (FXN)
• Harel-Yoon syndrome (ATAD3A)
• Hereditary motor + sensory neuropathy VIA (MFN2)
• Infantile cerebellar-retinal degeneration (ACO2)
• Leukodystrophy, hypomyelinating, 13 (HIKESHI)
• Leukodystrophy, hypomyelinating, 15 (EPRS1)
• Mitochondrial complex I deficiency, nuclear type 23 (NDUFA12)
• Mitochondrial complex I deficiency, nuclear type 5 (NDUFS1)
• Mitochondrial myopathy, episodic, with optic atrophy + reversible leukoencephalopathy (FDX2/FDX1L)
• Mohr-Tranebjaerg syndrome (TIMM8A)
• Multiple mitochondrial dysfunctions syndrome 4 (ISCA2)
• Neurodegeneration with brain iron accumulation 4 (19orf12)
• Neurodegeneration, childhood-onset, ataxia, tremor, optic atrophy, cognitive decline (SLC44A1)
• Neurodevelopmental disorder with visual defects + brain anomalies (HK1)
• Neuropathy, hereditary motor + sensory, Russe type (HK1)
• Neuropathy, hereditary motor + sensory, type VIB (SLC25A46)
• Optic atrophy 1 (OPA1)
• Optic atrophy 10 with/-out ataxia, mental retardation + seizures (RTN4IP1)
• Optic atrophy 12 (AFG3L2)
• Optic atrophy 13 with retinal + foveal abnormalities (SSBP1)
• Optic atrophy 3 with cataract (OPA3)
• Optic atrophy 5 (DNM1L)
• Optic atrophy 7 (TMEM126A)
• Optic atrophy 9 (ACO2)
• Optic atrophy plus syndrome (OPA1)
• Progressive external ophthalmoplegia, AD 1 (POLG)
• ROSAH [Retinal dystr., Opticus edema, Splenomegaly, Anhidrosis, migraine Headache] syndrome (ALPK1)
• Severe ID, global developmental delay, epilepsy [panelapp] (BLOC1S1)
• Short stature, optic nerve atrophy + Pelger-Huet anomaly (NBAS)
• Spastic ataxia 4, AR (MTPAP)
• Spastic paraplegia 35, AR (FA2H)
• Spastic paraplegia 43, AR (C19orf12)
• Spastic paraplegia 57, AR (TFG)
• Spastic paraplegia 7, AR (SPG7)
• Spastic paraplegia 75, AR (MAG)
• Spastic paraplegia 79, AR (UCHL)
• Spinocerebellar ataxia, AR 31 (ATG7)
• Wolfram syndrome 1 (WFS1)
• Wolfram syndrome 2 (CISD2)
• Wolfram-like syndrome, AD (WFS1)