IllnessOptic atrophy, hereditary; differential diagnosis

NGS +

[Sanger]

Optic atrophy or optic neuropathy is the end stage of a disease process affecting the retinogenic part of the visual pathway by neurovascular degeneration. Hereditary optic neuropathies are also characterized by degeneration of retinal ganglion cells, leading to bilateral optic atrophy and progressive loss of visual acuity. In addition, these patients often suffer from impaired color vision. The most common forms of hereditary optic neuropathies are dominant optic atrophy and Leber hereditary optic neuropathy. In both disorders, neuronal and axonal, the energy supply by mitochondria is affected. Optic atrophy can occur at any age, and all classical modes of inheritance are represented. The DNA diagnostic yield reaches approximately 20%. Therefore, inconspicuous molecular genetic findings do not mean exclusion of the suspected ophthalmologic diagnosis.

Reference: 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)