ICRD
MCID: INF129
MIFTS: 33

Infantile Cerebellar-Retinal Degeneration (ICRD)

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

Aliases & Classifications for Infantile Cerebellar-Retinal Degeneration

MalaCards integrated aliases for Infantile Cerebellar-Retinal Degeneration:

Name: Infantile Cerebellar-Retinal Degeneration 58 12 54 60 76 38 30 13 6 15 74
Icrd 58 54 76
Degeneration, Cerebellar-Retinal, Infantile 41
Infantile Cerebellar Retinal Degeneration 54

Characteristics:

Orphanet epidemiological data:

60
infantile cerebellar-retinal degeneration
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

58
Inheritance:
autosomal recessive

Miscellaneous:
onset in infancy


HPO:

33
infantile cerebellar-retinal degeneration:
Onset and clinical course infantile onset
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Infantile Cerebellar-Retinal Degeneration

NIH Rare Diseases : 54 Infantile cerebellar retinal degeneration (ICRD) is a genetic condition present from birth (congenital) that involves the brain and eyes. Individuals with this condition usually develop symptoms around six months of age including developmental delays, low muscle tone (hypotonia), and seizures. Other symptoms may include head bobbing, abnormal muscle twitching and movement, and loss of brain cells in the main part of the brain called the cerebellum. Eye findings in individuals with this condition may include retinal degeneration (weakening of the layer of tissue in the back of the eye that senses light), strabismus (crossed eyes), and nystagmus (fast, uncontrollable movements of the eyes). ICRD is caused by mutations in the ACO2 gene and is inherited in an autosomal recessive manner. While there is still no cure for this condition, treatment options will depend on the type and severity of symptoms. 

MalaCards based summary : Infantile Cerebellar-Retinal Degeneration, also known as icrd, is related to retinal degeneration and optic atrophy 9, and has symptoms including seizures, ataxia and athetosis. An important gene associated with Infantile Cerebellar-Retinal Degeneration is ACO2 (Aconitase 2), and among its related pathways/superpathways are Citrate cycle (TCA cycle) and Glyoxylate and dicarboxylate metabolism. Affiliated tissues include brain, eye and cerebellum, and related phenotypes are sensorineural hearing impairment and nystagmus

Disease Ontology : 12 A neurodegenerative disease that is characterized by onset between ages 2 and 6 months of truncal hypotonia, athetosis, seizures, and ophthalmologic abnormalities, particularly optic atrophy and retinal degeneration.

OMIM : 58 Infantile cerebellar-retinal degeneration is a severe autosomal recessive neurodegenerative disorder characterized by onset between ages 2 and 6 months of truncal hypotonia, athetosis, seizures, and ophthalmologic abnormalities, particularly optic atrophy and retinal degeneration. Affected individuals show profound psychomotor retardation, with only some achieving rolling, sitting, or recognition of family. Brain MRI shows progressive cerebral and cerebellar degeneration (summary by Spiegel et al., 2012). (614559)

UniProtKB/Swiss-Prot : 76 Infantile cerebellar-retinal degeneration: A severe autosomal recessive neurodegenerative disorder characterized by onset between ages 2 and 6 months of truncal hypotonia, athetosis, seizures, and ophthalmologic abnormalities, particularly optic atrophy and retinal degeneration. Affected individuals show profound psychomotor retardation, with only some achieving rolling, sitting, or recognition of family. Brain MRI shows progressive cerebral and cerebellar degeneration.

Related Diseases for Infantile Cerebellar-Retinal Degeneration

Diseases related to Infantile Cerebellar-Retinal Degeneration via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 retinal degeneration 10.1
2 optic atrophy 9 9.4 ACO2 POLR3H

Symptoms & Phenotypes for Infantile Cerebellar-Retinal Degeneration

Human phenotypes related to Infantile Cerebellar-Retinal Degeneration:

33 (show all 19)
# Description HPO Frequency HPO Source Accession
1 sensorineural hearing impairment 33 occasional (7.5%) HP:0000407
2 nystagmus 33 HP:0000639
3 seizures 33 HP:0001250
4 ataxia 33 HP:0001251
5 failure to thrive 33 HP:0001508
6 optic atrophy 33 HP:0000648
7 intellectual disability, severe 33 HP:0010864
8 strabismus 33 HP:0000486
9 severe global developmental delay 33 HP:0011344
10 cerebral cortical atrophy 33 HP:0002120
11 areflexia 33 HP:0001284
12 hyporeflexia 33 HP:0001265
13 cerebellar atrophy 33 HP:0001272
14 generalized hypotonia 33 HP:0001290
15 hypoplasia of the corpus callosum 33 HP:0002079
16 retinal dystrophy 33 HP:0000556
17 athetosis 33 HP:0002305
18 demyelinating peripheral neuropathy 33 HP:0007108
19 progressive microcephaly 33 HP:0000253

Symptoms via clinical synopsis from OMIM:

58
Head And Neck Eyes:
nystagmus
optic atrophy
strabismus
retinal dystrophy
abnormal pursuit

Growth Other:
failure to thrive

Growth Weight:
low weight

Head And Neck Ears:
hearing loss, sensorineural (in 2 patients)

Neurologic Central Nervous System:
seizures
ataxia
athetosis
hypotonia
thin corpus callosum
more
Neurologic Peripheral Nervous System:
areflexia
hyporeflexia
peripheral demyelinating neuropathy

Head And Neck Head:
microcephaly, progressive

Muscle Soft Tissue:
decreased glutamate oxidation (about 63% of normal)

Clinical features from OMIM:

614559

UMLS symptoms related to Infantile Cerebellar-Retinal Degeneration:


seizures, ataxia, athetosis

Drugs & Therapeutics for Infantile Cerebellar-Retinal Degeneration

Search Clinical Trials , NIH Clinical Center for Infantile Cerebellar-Retinal Degeneration

Genetic Tests for Infantile Cerebellar-Retinal Degeneration

Genetic tests related to Infantile Cerebellar-Retinal Degeneration:

# Genetic test Affiliating Genes
1 Infantile Cerebellar-Retinal Degeneration 30 ACO2

Anatomical Context for Infantile Cerebellar-Retinal Degeneration

MalaCards organs/tissues related to Infantile Cerebellar-Retinal Degeneration:

42
Brain, Eye, Cerebellum

Publications for Infantile Cerebellar-Retinal Degeneration

Articles related to Infantile Cerebellar-Retinal Degeneration:

# Title Authors Year
1
Mutations in the tricarboxylic acid cycle enzyme, aconitase 2, cause either isolated or syndromic optic neuropathy with encephalopathy and cerebellar atrophy. ( 25351951 )
2014
2
Infantile cerebellar-retinal degeneration associated with a mutation in mitochondrial aconitase, ACO2. ( 22405087 )
2012

Variations for Infantile Cerebellar-Retinal Degeneration

UniProtKB/Swiss-Prot genetic disease variations for Infantile Cerebellar-Retinal Degeneration:

76
# Symbol AA change Variation ID SNP ID
1 ACO2 p.Ser112Arg VAR_067543 rs786200924
2 ACO2 p.Gly259Asp VAR_073436 rs786204828
3 ACO2 p.Lys736Asn VAR_073438 rs786204829

ClinVar genetic disease variations for Infantile Cerebellar-Retinal Degeneration:

6 (show all 30)
# Gene Variation Type Significance SNP ID Assembly Location
1 ACO2 NM_001098.2(ACO2): c.336C> G (p.Ser112Arg) single nucleotide variant Pathogenic rs786200924 GRCh37 Chromosome 22, 41903957: 41903957
2 ACO2 NM_001098.2(ACO2): c.336C> G (p.Ser112Arg) single nucleotide variant Pathogenic rs786200924 GRCh38 Chromosome 22, 41507953: 41507953
3 ACO2 NM_001098.2(ACO2): c.220C> G (p.Leu74Val) single nucleotide variant Conflicting interpretations of pathogenicity rs141772938 GRCh37 Chromosome 22, 41903841: 41903841
4 ACO2 NM_001098.2(ACO2): c.220C> G (p.Leu74Val) single nucleotide variant Conflicting interpretations of pathogenicity rs141772938 GRCh38 Chromosome 22, 41507837: 41507837
5 ACO2 NM_001098.2(ACO2): c.776G> A (p.Gly259Asp) single nucleotide variant Pathogenic rs786204828 GRCh37 Chromosome 22, 41911862: 41911862
6 ACO2 NM_001098.2(ACO2): c.776G> A (p.Gly259Asp) single nucleotide variant Pathogenic rs786204828 GRCh38 Chromosome 22, 41515858: 41515858
7 ACO2 NM_001098.2(ACO2): c.2208G> C (p.Lys736Asn) single nucleotide variant Pathogenic rs786204829 GRCh37 Chromosome 22, 41924026: 41924026
8 ACO2 NM_001098.2(ACO2): c.2208G> C (p.Lys736Asn) single nucleotide variant Pathogenic rs786204829 GRCh38 Chromosome 22, 41528022: 41528022
9 ACO2 NM_001098.2(ACO2): c.2328_2331delGGAA (p.Lys776Asnfs) deletion Pathogenic rs786204830 GRCh37 Chromosome 22, 41924602: 41924605
10 ACO2 NM_001098.2(ACO2): c.2328_2331delGGAA (p.Lys776Asnfs) deletion Pathogenic rs786204830 GRCh38 Chromosome 22, 41528598: 41528601
11 ACO2 NM_001098.2(ACO2): c.719G> C (p.Gly240Ala) single nucleotide variant Uncertain significance rs141878785 GRCh38 Chromosome 22, 41515801: 41515801
12 ACO2 NM_001098.2(ACO2): c.719G> C (p.Gly240Ala) single nucleotide variant Uncertain significance rs141878785 GRCh37 Chromosome 22, 41911805: 41911805
13 ACO2 NM_001098.2(ACO2): c.2051G> A (p.Arg684Gln) single nucleotide variant Uncertain significance rs200345386 GRCh38 Chromosome 22, 41527385: 41527385
14 ACO2 NM_001098.2(ACO2): c.2051G> A (p.Arg684Gln) single nucleotide variant Uncertain significance rs200345386 GRCh37 Chromosome 22, 41923389: 41923389
15 ACO2 NM_001098.2(ACO2): c.1819C> T (p.Arg607Cys) single nucleotide variant Likely pathogenic rs864309499 GRCh37 Chromosome 22, 41922323: 41922323
16 ACO2 NM_001098.2(ACO2): c.1819C> T (p.Arg607Cys) single nucleotide variant Likely pathogenic rs864309499 GRCh38 Chromosome 22, 41526319: 41526319
17 ACO2 NM_001098.2(ACO2): c.2135C> T (p.Pro712Leu) single nucleotide variant Likely pathogenic rs375761361 GRCh37 Chromosome 22, 41923953: 41923953
18 ACO2 NM_001098.2(ACO2): c.2135C> T (p.Pro712Leu) single nucleotide variant Likely pathogenic rs375761361 GRCh38 Chromosome 22, 41527949: 41527949
19 ACO2 NM_001098.2(ACO2): c.2337_2338del (p.Gln780Valfs) deletion Pathogenic rs1114167284 GRCh38 Chromosome 22, 41528607: 41528608
20 ACO2 NM_001098.2(ACO2): c.2337_2338del (p.Gln780Valfs) deletion Pathogenic rs1114167284 GRCh37 Chromosome 22, 41924611: 41924612
21 ACO2 NM_001098.2(ACO2): c.1550C> T (p.Thr517Met) single nucleotide variant Likely pathogenic rs540169523 GRCh38 Chromosome 22, 41524913: 41524913
22 ACO2 NM_001098.2(ACO2): c.1550C> T (p.Thr517Met) single nucleotide variant Likely pathogenic rs540169523 GRCh37 Chromosome 22, 41920917: 41920917
23 ACO2 NM_001098.2(ACO2): c.2050C> T (p.Arg684Trp) single nucleotide variant Uncertain significance GRCh38 Chromosome 22, 41527384: 41527384
24 ACO2 NM_001098.2(ACO2): c.2050C> T (p.Arg684Trp) single nucleotide variant Uncertain significance GRCh37 Chromosome 22, 41923388: 41923388
25 ACO2 NM_001098.2(ACO2): c.2153T> C (p.Ile718Thr) single nucleotide variant Uncertain significance GRCh38 Chromosome 22, 41527967: 41527967
26 ACO2 NM_001098.2(ACO2): c.2153T> C (p.Ile718Thr) single nucleotide variant Uncertain significance GRCh37 Chromosome 22, 41923971: 41923971
27 ACO2 NM_001098.2(ACO2): c.2026C> G (p.Leu676Val) single nucleotide variant Uncertain significance GRCh37 Chromosome 22, 41923364: 41923364
28 ACO2 NM_001098.2(ACO2): c.2026C> G (p.Leu676Val) single nucleotide variant Uncertain significance GRCh38 Chromosome 22, 41527360: 41527360
29 ACO2 NM_001098.3(ACO2): c.1285C> T (p.Arg429Trp) single nucleotide variant Uncertain significance GRCh38 Chromosome 22, 41522976: 41522976
30 ACO2 NM_001098.3(ACO2): c.1285C> T (p.Arg429Trp) single nucleotide variant Uncertain significance GRCh37 Chromosome 22, 41918980: 41918980

Expression for Infantile Cerebellar-Retinal Degeneration

Search GEO for disease gene expression data for Infantile Cerebellar-Retinal Degeneration.

Pathways for Infantile Cerebellar-Retinal Degeneration

Pathways related to Infantile Cerebellar-Retinal Degeneration according to KEGG:

38
# Name Kegg Source Accession
1 Citrate cycle (TCA cycle) hsa00020
2 Glyoxylate and dicarboxylate metabolism hsa00630

GO Terms for Infantile Cerebellar-Retinal Degeneration

Biological processes related to Infantile Cerebellar-Retinal Degeneration according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 tricarboxylic acid cycle GO:0006099 8.96 ACO1 ACO2
2 citrate metabolic process GO:0006101 8.62 ACO1 ACO2

Molecular functions related to Infantile Cerebellar-Retinal Degeneration according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 lyase activity GO:0016829 9.32 ACO1 ACO2
2 iron-sulfur cluster binding GO:0051536 9.26 ACO1 ACO2
3 4 iron, 4 sulfur cluster binding GO:0051539 9.16 ACO1 ACO2
4 3 iron, 4 sulfur cluster binding GO:0051538 8.96 ACO1 ACO2
5 aconitate hydratase activity GO:0003994 8.62 ACO1 ACO2

Sources for Infantile Cerebellar-Retinal Degeneration

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
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