MCID: OPT055
MIFTS: 50

Optic Atrophy Plus Syndrome

Categories: Genetic diseases, Eye diseases, Neuronal diseases, Ear diseases, Rare diseases, Metabolic diseases

Aliases & Classifications for Optic Atrophy Plus Syndrome

MalaCards integrated aliases for Optic Atrophy Plus Syndrome:

Name: Optic Atrophy Plus Syndrome 54
Optic Atrophy 12 29 52 42 14 69
Optic Atrophy with or Without Deafness, Ophthalmoplegia, Myopathy, Ataxia, and Neuropathy 69
Optic Atrophy with or Without Deafness Ophthalmoplegia Myopathy Ataxia and Neuropathy 71
Dominant Optic Atrophy Plus Syndrome 71
3-Methylglutaconic Aciduria Type 3 69
Atrophy of Optic Disc 12
Doa+ 71

Characteristics:

OMIM:

54
Inheritance:
autosomal dominant

Miscellaneous:
progressive disorder
variable phenotype
variable age of onset (childhood to adult)


HPO:

32
optic atrophy plus syndrome:
Onset and clinical course phenotypic variability
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Optic Atrophy Plus Syndrome

OMIM : 54
Syndromic optic atrophy, also known as DOA+ syndrome, is a neurologic disorder characterized most commonly by an insidious onset of visual loss and sensorineural hearing loss in childhood with variable presentation of other clinical manifestations including progressive external ophthalmoplegia (PEO), muscle cramps, hyperreflexia, and ataxia. There appears to be a wide range of intermediate phenotypes (Yu-Wai-Man et al., 2010). (125250)

MalaCards based summary : Optic Atrophy Plus Syndrome, also known as optic atrophy, is related to optic atrophy 1 and leber optic atrophy, and has symptoms including visual impairment, optic atrophy and ataxia. An important gene associated with Optic Atrophy Plus Syndrome is OPA1 (OPA1, Mitochondrial Dynamin Like GTPase), and among its related pathways/superpathways is Glucose / Energy Metabolism. The drugs Acetylcysteine and Deferiprone have been mentioned in the context of this disorder. Affiliated tissues include brain and eye, and related phenotypes are behavior/neurological and cellular

UniProtKB/Swiss-Prot : 71 Dominant optic atrophy plus syndrome: A neurologic disorder characterized most commonly by an insidious onset of visual loss and sensorineural hearing loss in childhood with variable presentation of other clinical manifestations including progressive external ophthalmoplegia, muscle cramps, hyperreflexia, and ataxia. There appears to be a wide range of intermediate phenotypes.

Related Diseases for Optic Atrophy Plus Syndrome

Diseases in the Primary Optic Atrophy family:

Optic Atrophy 1 Optic Atrophy Plus Syndrome
Optic Atrophy 6 Optic Atrophy 11
Optic Atrophy 7 Optic Atrophy 8
Optic Atrophy 4 Optic Atrophy 5
Optic Atrophy 9 Optic Atrophy 2
Autosomal Dominant Optic Atrophy Plus Syndrome

Diseases related to Optic Atrophy Plus Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 28)
id Related Disease Score Top Affiliating Genes
1 optic atrophy 1 12.5
2 leber optic atrophy 12.5
3 autosomal dominant optic atrophy plus syndrome 12.3
4 glaucomatous atrophy of optic disc 12.1
5 3-methylglutaconic aciduria, type iii 11.4
6 optic atrophy 3 with cataract 11.2
7 megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1 10.8 OPA3 PMPCA
8 hereditary motor and sensory neuropathy via 10.7 C12orf65 MFN2
9 glaucoma, normal tension 10.7 MFN2 OPA1
10 viral infectious disease 10.6 MT-ND4 OPA1 TMEM126A
11 leiner disease 10.6 MT-ND4 MT-ND6
12 toxic maculopathy 10.6 ANTXR1 MFF
13 lmna-related emery-dreifuss muscular dystrophy, autosomal 10.6 C12orf65 OPA3
14 pancreatic acinar cell adenocarcinoma 10.5 MFN2 MT-ND4 MT-ND6
15 3-m syndrome 3 10.5 OPA3 PMPCA
16 deafness, autosomal dominant 6/14/38 10.4 BAMBI CISD2 WFS1
17 enchondromatosis dwarfism deafness 10.4 MT-ND4 MT-ND6
18 protoplasmic astrocytoma 10.4 C12orf65 MT-ND4 MT-ND6
19 mitochondrial dna depletion syndrome 14 10.4 C12orf65 C19orf12 OPA1 OPA3
20 multiminicore disease 10.3 MT-ND4 MT-ND6 OPA1
21 dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema 10.2 MFN1 MFN2 OPA1 YME1L1
22 scrapie 10.1 ATP1A3 C19orf12 MT-ND4 MT-ND6
23 mitochondrial neurogastrointestinal encephalopathy disease 10.1 MT-ND4 MT-ND6
24 androgen insensitivity 10.0 MT-ND4 MT-ND6 OPA1 OPA3 OPN4 TMEM126A
25 3-methylglutaconic aciduria 9.7
26 pleomorphic carcinoma 9.5 ANTXR1 DNM1L MFN1 MFN2 MT-ND4 MT-ND6
27 allergic contact dermatitis of eyelid 9.2 ANTXR1 BTD DNM1L MFN1 MFN2 MT-ND4
28 behr syndrome 6.8 ANTXR1 ATP1A3 BAMBI BTD C12orf65 C19orf12

Graphical network of the top 20 diseases related to Optic Atrophy Plus Syndrome:



Diseases related to Optic Atrophy Plus Syndrome

Symptoms & Phenotypes for Optic Atrophy Plus Syndrome

Symptoms via clinical synopsis from OMIM:

54

Head And Neck- Eyes:
optic atrophy
strabismus
horizontal nystagmus
ptosis
decreased visual acuity
more
Head And Neck- Ears:
hearing loss, progressive sensorineural
absent or decreased auditory brainstem responses
auditory neuropathy

Neurologic- Peripheral Nervous System:
axonal sensorineural polyneuropathy

Neurologic- Central Nervous System:
spasticity (in some patients)
cerebellar ataxia (in some patients)
gait difficulties (in some patients)

Muscle Soft Tissue:
ragged red fibers
myopathy, mild
increased fiber size variation
mitochondrial dna deletions (in some patients)


Clinical features from OMIM:

125250

Human phenotypes related to Optic Atrophy Plus Syndrome:

32 (show all 18)
id Description HPO Frequency HPO Source Accession
1 visual impairment 32 HP:0000505
2 optic atrophy 32 HP:0000648
3 ataxia 32 occasional (7.5%) HP:0001251
4 strabismus 32 HP:0000486
5 horizontal nystagmus 32 HP:0000666
6 ptosis 32 HP:0000508
7 peripheral neuropathy 32 HP:0009830
8 reduced visual acuity 32 HP:0007663
9 myopathy 32 HP:0003198
10 central scotoma 32 HP:0000603
11 ophthalmoplegia 32 HP:0000602
12 red-green dyschromatopsia 32 HP:0000642
13 centrocecal scotoma 32 HP:0000576
14 abnormal auditory evoked potentials 32 HP:0006958
15 increased variability in muscle fiber diameter 32 HP:0003557
16 progressive sensorineural hearing impairment 32 HP:0000408
17 tritanomaly 32 HP:0000552
18 abnormal amplitude of pattern reversal visual evoked potentials 32 HP:0000650

UMLS symptoms related to Optic Atrophy Plus Syndrome:


ataxia, muscle spasticity, abnormality of extrapyramidal motor function, ophthalmoplegia

MGI Mouse Phenotypes related to Optic Atrophy Plus Syndrome:

44
id Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 10 ATP1A3 BAMBI BTD CISD2 DNM1L MFN1
2 cellular MP:0005384 9.85 ANTXR1 CISD2 DNM1L MFN1 MFN2 MT-ND6
3 growth/size/body region MP:0005378 9.73 DNM1L MFN1 MFN2 OPA1 OPA3 WFS1
4 muscle MP:0005369 9.23 ATP1A3 BTD CISD2 DNM1L MFN2 OPA1

Drugs & Therapeutics for Optic Atrophy Plus Syndrome

Drugs for Optic Atrophy Plus Syndrome (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 43)
id Name Status Phase Clinical Trials Cas Number PubChem Id
1
Acetylcysteine Approved, Investigational Phase 2, Phase 3 616-91-1 12035
2
Deferiprone Approved Phase 2, Phase 3 30652-11-0 2972
3
Iron Approved Phase 2, Phase 3 7439-89-6 23925
4
Metformin Approved Phase 2, Phase 3 657-24-9 14219 4091
5
Riluzole Approved, Investigational Phase 3 1744-22-5 5070
6
Armodafinil Approved, Investigational Phase 3 112111-43-0
7
Modafinil Approved, Investigational Phase 3 68693-11-8 4236
8 Hormone Antagonists Phase 2, Phase 3
9 Hormones Phase 2, Phase 3
10 Hormones, Hormone Substitutes, and Hormone Antagonists Phase 2, Phase 3
11 Hypoglycemic Agents Phase 2, Phase 3
12 Incretins Phase 2, Phase 3
13 Epoetin alfa Phase 3 113427-24-0
14 Hematinics Phase 3
15 Antidotes Phase 2, Phase 3
16 Anti-Infective Agents Phase 2, Phase 3
17 Antioxidants Phase 2, Phase 3
18 Antiviral Agents Phase 2, Phase 3
19 Chelating Agents Phase 2, Phase 3
20 Dipeptidyl-Peptidase IV Inhibitors Phase 2, Phase 3
21 Expectorants Phase 2, Phase 3
22 HIV Protease Inhibitors Phase 2, Phase 3
23 Iron Chelating Agents Phase 2, Phase 3
24 N-monoacetylcystine Phase 2, Phase 3
25
protease inhibitors Phase 2, Phase 3
26 Protective Agents Phase 2, Phase 3
27 Respiratory System Agents Phase 2, Phase 3
28 Sitagliptin Phosphate Phase 2, Phase 3
29 Anticonvulsants Phase 3
30 Excitatory Amino Acid Antagonists Phase 3
31 Excitatory Amino Acids Phase 3
32 Neuroprotective Agents Phase 3
33 Neurotransmitter Agents Phase 3
34 Central Nervous System Stimulants Phase 3
35 Cytochrome P-450 CYP3A Inducers Phase 3
36 Wakefulness-Promoting Agents Phase 3
37
Dantrolene Approved Phase 1, Phase 2 7261-97-4 2952 6914273
38 Neuromuscular Agents Phase 1, Phase 2
39 Peripheral Nervous System Agents Phase 1, Phase 2
40
Exenatide Approved, Investigational 141758-74-9 15991534
41 Glucagon-Like Peptide 1
42 insulin
43 Insulin, Globin Zinc

Interventional clinical trials:

(show all 12)

id Name Status NCT ID Phase Drugs
1 Treatment of Optic Neuritis With Erythropoietin: a Randomised, Double-blind, Placebo-controlled Trial Active, not recruiting NCT01962571 Phase 3 Erythropoietin alfa;Placebo
2 Treatment of Wolfram Syndrome Type 2 With the Chelator Deferiprone and Incretin Based Therapy Not yet recruiting NCT02882477 Phase 2, Phase 3 Deferiprone;Acetylcysteine;Sitagliptin and Metformin
3 Neuroprotection and Natural History in Parkinson's Plus Syndromes (NNIPPS) Terminated NCT00211224 Phase 3 Riluzole
4 Modafinil to Treat Fatigue in Post-Polio Syndrome Terminated NCT00067496 Phase 3 Modafinil
5 A Clinical Trial of Dantrolene Sodium in Pediatric and Adult Patients With Wolfram Syndrome Recruiting NCT02829268 Phase 1, Phase 2 dantrolene sodium
6 GLP Analogs for Diabetes in Wolfram Syndrome Patients Unknown status NCT01302327 Exenatide
7 Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford Recruiting NCT01793168
8 Wolfram Syndrome International Registry and Clinical Study Recruiting NCT02841553
9 Tracking Neurodegeneration in Early Wolfram Syndrome Recruiting NCT02455414
10 PROgressive Supranuclear Palsy CorTico-Basal Syndrome Multiple System Atrophy Longitudinal Study UK Recruiting NCT02778607
11 Stem Cell Ophthalmology Treatment Study II Recruiting NCT03011541
12 Brain Network Activation in Patients With Movement Disorders Not yet recruiting NCT03269201

Search NIH Clinical Center for Optic Atrophy Plus Syndrome

Cochrane evidence based reviews: optic atrophy

Genetic Tests for Optic Atrophy Plus Syndrome

Genetic tests related to Optic Atrophy Plus Syndrome:

id Genetic test Affiliating Genes
1 Optic Atrophy 29

Anatomical Context for Optic Atrophy Plus Syndrome

MalaCards organs/tissues related to Optic Atrophy Plus Syndrome:

39
Brain, Eye

Publications for Optic Atrophy Plus Syndrome

Articles related to Optic Atrophy Plus Syndrome:

id Title Authors Year
1
Type III 3-methylglutaconic aciduria (optic atrophy plus syndrome, or Costeff optic atrophy syndrome): identification of the OPA3 gene and its founder mutation in Iraqi Jews. ( 11668429 )
2001

Variations for Optic Atrophy Plus Syndrome

UniProtKB/Swiss-Prot genetic disease variations for Optic Atrophy Plus Syndrome:

71
id Symbol AA change Variation ID SNP ID
1 OPA1 p.Arg445His VAR_015741 rs80356529
2 OPA1 p.Ser545Arg VAR_026533 rs398124298
3 OPA1 p.Ala357Thr VAR_060836 rs190223702
4 OPA1 p.Cys551Tyr VAR_060851 rs879255592
5 OPA1 p.Tyr582Cys VAR_060853 rs121908376
6 OPA1 p.Gly439Val VAR_072127 rs387906900
7 OPA1 p.Thr449Pro VAR_072128
8 OPA1 p.Val910Asp VAR_072132 rs387906901

ClinVar genetic disease variations for Optic Atrophy Plus Syndrome:

6 (show all 13)
id Gene Variation Type Significance SNP ID Assembly Location
1 OPA1 NM_015560.2(OPA1): c.1745A> G (p.Tyr582Cys) single nucleotide variant Pathogenic rs121908376 GRCh37 Chromosome 3, 193365898: 193365898
2 OPA1 NM_015560.2(OPA1): c.1334G> A (p.Arg445His) single nucleotide variant Pathogenic rs80356529 GRCh37 Chromosome 3, 193361785: 193361785
3 OPA1 NM_015560.2(OPA1): c.2848_2849delGA (p.Asp950Cysfs) deletion Pathogenic rs879255513 GRCh38 Chromosome 3, 193692092: 193692093
4 OPA1 NM_015560.2(OPA1): c.1294A> G (p.Ile432Val) single nucleotide variant Pathogenic rs387906899 GRCh37 Chromosome 3, 193361398: 193361398
5 OPA1 NM_015560.2(OPA1): c.1635C> G (p.Ser545Arg) single nucleotide variant Pathogenic rs398124298 GRCh37 Chromosome 3, 193364899: 193364899
6 OPA1 NM_015560.2(OPA1): c.1316G> T (p.Gly439Val) single nucleotide variant Pathogenic rs387906900 GRCh37 Chromosome 3, 193361767: 193361767
7 OPA1 NM_015560.2(OPA1): c.2729T> A (p.Val910Asp) single nucleotide variant Pathogenic rs387906901 GRCh37 Chromosome 3, 193384980: 193384980
8 ISCA2 NM_194279.3(ISCA2): c.229G> A (p.Gly77Ser) single nucleotide variant Pathogenic/Likely pathogenic rs730882246 GRCh38 Chromosome 14, 74494329: 74494329
9 OPA1 NM_015560.2(OPA1): c.1346delC (p.Thr449Lysfs) deletion Likely pathogenic rs794729196 GRCh37 Chromosome 3, 193361797: 193361797
10 PMPCA NM_015160.2(PMPCA): c.1066G> A (p.Gly356Ser) single nucleotide variant Pathogenic rs768643552 GRCh37 Chromosome 9, 139313082: 139313082
11 PMPCA NM_015160.2(PMPCA): c.1129G> A (p.Ala377Thr) single nucleotide variant Pathogenic rs753611141 GRCh38 Chromosome 9, 136418847: 136418847
12 OPA1 NM_130837.2(OPA1): c.1817G> A (p.Cys606Tyr) single nucleotide variant Pathogenic rs879255592 GRCh37 Chromosome 3, 193364916: 193364916
13 OPA1 NM_015560.2(OPA1): c.985-2A> G single nucleotide variant Pathogenic rs886041317 GRCh37 Chromosome 3, 193360552: 193360552

Copy number variations for Optic Atrophy Plus Syndrome from CNVD:

7
id CNVD ID Chromosom Start End Type Gene Symbol CNVD Disease
1 173060 3 189400000 193800000 Deletion OPA1 Optic atrophy

Expression for Optic Atrophy Plus Syndrome

Search GEO for disease gene expression data for Optic Atrophy Plus Syndrome.

Pathways for Optic Atrophy Plus Syndrome

Pathways related to Optic Atrophy Plus Syndrome according to GeneCards Suite gene sharing:

id Super pathways Score Top Affiliating Genes
1 11.49 CISD2 MFN1 MFN2 OPA1 WFS1

GO Terms for Optic Atrophy Plus Syndrome

Cellular components related to Optic Atrophy Plus Syndrome according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 mitochondrial inner membrane GO:0005743 9.63 MT-ND4 MT-ND6 OPA1 PMPCA TMEM126A YME1L1
2 mitochondrial membrane GO:0031966 9.54 C19orf12 MT-ND4 MT-ND6
3 mitochondrion GO:0005739 9.44 C12orf65 C19orf12 CISD2 DNM1L MFF MFN1
4 mitochondrial outer membrane GO:0005741 9.43 CISD2 DNM1L MFF MFN1 MFN2 OPA1
5 membrane GO:0016020 10.25 ANTXR1 ATP1A3 BAMBI C19orf12 CISD2 DNM1L
6 integral component of membrane GO:0016021 10.13 ANTXR1 ATP1A3 BAMBI C19orf12 CISD2 MFF

Biological processes related to Optic Atrophy Plus Syndrome according to GeneCards Suite gene sharing:

(show all 18)
id Name GO ID Score Top Affiliating Genes
1 visual perception GO:0007601 9.71 OPA1 OPA3 OPN4 WFS1
2 mitochondrion organization GO:0007005 9.69 DNM1L OPA1 YME1L1
3 mitochondrial calcium ion transport GO:0006851 9.58 PMPCA YME1L1
4 release of cytochrome c from mitochondria GO:0001836 9.57 DNM1L MFF
5 positive regulation of dendritic spine morphogenesis GO:0061003 9.56 DNM1L OPA1
6 negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway GO:1902236 9.55 OPA1 WFS1
7 positive regulation of mitochondrial fission GO:0090141 9.54 DNM1L MFF
8 regulation of mitochondrion organization GO:0010821 9.52 DNM1L MFF
9 peroxisome fission GO:0016559 9.48 DNM1L MFF
10 mitochondrial fragmentation involved in apoptotic process GO:0043653 9.46 DNM1L MFF
11 dynamin family protein polymerization involved in mitochondrial fission GO:0003374 9.43 DNM1L OPA1
12 mitochondrion localization GO:0051646 9.37 MFN1 MFN2
13 mitochondrial fission GO:0000266 9.33 DNM1L MFF OPA1
14 intracellular distribution of mitochondria GO:0048312 9.32 DNM1L OPA1
15 regulation of peroxisome organization GO:1900063 9.26 DNM1L MFF
16 mitochondrion morphogenesis GO:0070584 9.26 DNM1L MFF OPA1 OPA3
17 GTP metabolic process GO:0046039 9.19 MFN1
18 mitochondrial fusion GO:0008053 8.92 MFF MFN1 MFN2 OPA1

Molecular functions related to Optic Atrophy Plus Syndrome according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 GTPase activity GO:0003924 9.26 DNM1L MFN1 MFN2 OPA1
2 hydrolase activity GO:0016787 9.23 ATP1A3 BTD DNM1L MFN1 MFN2 OPA1

Sources for Optic Atrophy Plus Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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