MCID: ACR091
MIFTS: 32

Aicardi-Goutieres Syndrome 4

Categories: Genetic diseases, Rare diseases, Neuronal diseases, Immune diseases, Bone diseases, Blood diseases

Aliases & Classifications for Aicardi-Goutieres Syndrome 4

MalaCards integrated aliases for Aicardi-Goutieres Syndrome 4:

Name: Aicardi-Goutieres Syndrome 4 57 75 13 73
Ags4 57 53 75
Aicardi Goutieres Syndrome 4 29 6
Pseudo-Torch Syndrome 75 73
Rnaseh2a-Related Aicardi-Goutieres Syndrome 53
Aicardi-Goutieres Syndrome, Type 4 40
Aicardi-Goutieres Syndrome Type 4 53
Aicardi-Goutieres Syndrome 1 73
Cree Encephalitis 75

Characteristics:

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
onset in first year of life


HPO:

32
aicardi-goutieres syndrome 4:
Onset and clinical course infantile onset
Mortality/Aging death in childhood
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Aicardi-Goutieres Syndrome 4

NIH Rare Diseases : 53 Aicardi-Goutieres syndrome is an inherited disease that mainly affects the brain, immune system, and the skin. Loss of white matter in the brain (leukodystrophy) and abnormal deposits of calcium (calcification) in the brain leads to an early-onset severe brain dysfunction (encephalopathy) that usually results in severe intellectual and physical disability.  Additional symptoms may include epilepsy, painful, itchy skin lesion (chilblains), vision problems, and joint and muscle stiffness (spasticity), involuntary muscle twisting and contractions (dystonia), and weak muscle tone (hypotonia) in the torso. Other signs and symptoms may include a very small head (microcephaly), presence of white blood cells and other sign of inflammation in the  cerebrospinal fluid, which is the fluid that surrounds the brain and spinal cord (central nervous system). Symptoms usually progress over several months before the disease course stabilizes.  There are several types of Aicardi-Goutieres syndrome, depending on the gene that causes the condition: TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR and IFIH1, genes. Most cases are inherited in an autosomal recessive pattern, although rare autosomal dominant cases have been reported. Treatment is symptomatic and supportive. The prognosis depends mainly on the severity neurologic problems and in the age of onset of these problems.

MalaCards based summary : Aicardi-Goutieres Syndrome 4, also known as ags4, is related to pseudo-torch syndrome 1 and pseudo-torch syndrome 2, and has symptoms including seizures, petechiae of skin and muscle spasticity. An important gene associated with Aicardi-Goutieres Syndrome 4 is RNASEH2A (Ribonuclease H2 Subunit A). Affiliated tissues include skin, brain and spinal cord, and related phenotypes are low-set ears and hydrocephalus

UniProtKB/Swiss-Prot : 75 Aicardi-Goutieres syndrome 4: A form of Aicardi-Goutieres syndrome, a genetically heterogeneous disease characterized by cerebral atrophy, leukoencephalopathy, intracranial calcifications, chronic cerebrospinal fluid (CSF) lymphocytosis, increased CSF alpha-interferon, and negative serologic investigations for common prenatal infection. Clinical features as thrombocytopenia, hepatosplenomegaly and elevated hepatic transaminases along with intermittent fever may erroneously suggest an infective process. Severe neurological dysfunctions manifest in infancy as progressive microcephaly, spasticity, dystonic posturing and profound psychomotor retardation. Death often occurs in early childhood.

Description from OMIM: 610333

Related Diseases for Aicardi-Goutieres Syndrome 4

Diseases in the Aicardi-Goutieres Syndrome family:

Aicardi-Goutieres Syndrome 1 Aicardi-Goutieres Syndrome 2
Aicardi-Goutieres Syndrome 3 Aicardi-Goutieres Syndrome 4
Aicardi-Goutieres Syndrome 5 Aicardi-Goutieres Syndrome 6
Aicardi-Goutieres Syndrome 7

Diseases related to Aicardi-Goutieres Syndrome 4 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 pseudo-torch syndrome 1 12.7
2 pseudo-torch syndrome 2 12.7
3 aicardi-goutieres syndrome 1 12.0
4 aicardi-goutieres syndrome 11.3
5 aicardi-goutieres syndrome 2 11.1
6 aicardi-goutieres syndrome 3 11.1
7 aicardi-goutieres syndrome 5 11.1
8 aicardi-goutieres syndrome 6 11.1
9 encephalitis 9.9

Graphical network of the top 20 diseases related to Aicardi-Goutieres Syndrome 4:



Diseases related to Aicardi-Goutieres Syndrome 4

Symptoms & Phenotypes for Aicardi-Goutieres Syndrome 4

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Ears:
low-set ears
anteriorly rotated ears

AbdomenSpleen:
splenomegaly

Head And Neck Head:
microcephaly

Growth Other:
intrauterine growth retardation

Head And Neck Eyes:
visual inattention

Head And Neck Nose:
hooked nose

Immunology:
no evidence of prenatal infection

Neurologic Central Nervous System:
hydrocephalus
spasticity
cerebellar atrophy
cerebral atrophy
leukodystrophy
more
Abdomen Liver:
hepatomegaly
abnormal liver function tests

Hematology:
pancytopenia

Abdomen Gastrointestinal:
poor feeding

Laboratory Abnormalities:
increased serum alpha-interferon (ifna1, )
csf lymphocytosis
increased csf interferon

Respiratory Lung:
respiratory insufficiency in neonatal period


Clinical features from OMIM:

610333

Human phenotypes related to Aicardi-Goutieres Syndrome 4:

32 (show all 21)
# Description HPO Frequency HPO Source Accession
1 low-set ears 32 HP:0000369
2 hydrocephalus 32 HP:0000238
3 spasticity 32 HP:0001257
4 cerebral calcification 32 HP:0002514
5 splenomegaly 32 HP:0001744
6 hepatomegaly 32 HP:0002240
7 pancytopenia 32 HP:0001876
8 feeding difficulties 32 HP:0011968
9 severe global developmental delay 32 HP:0011344
10 intrauterine growth retardation 32 HP:0001511
11 elevated hepatic transaminases 32 HP:0002910
12 dystonia 32 HP:0001332
13 thrombocytopenia 32 HP:0001873
14 ventriculomegaly 32 HP:0002119
15 convex nasal ridge 32 HP:0000444
16 cerebellar atrophy 32 HP:0001272
17 cerebral atrophy 32 HP:0002059
18 leukodystrophy 32 HP:0002415
19 hepatosplenomegaly 32 HP:0001433
20 progressive microcephaly 32 HP:0000253
21 csf lymphocytic pleiocytosis 32 HP:0200149

UMLS symptoms related to Aicardi-Goutieres Syndrome 4:


seizures, petechiae of skin, muscle spasticity

Drugs & Therapeutics for Aicardi-Goutieres Syndrome 4

Search Clinical Trials , NIH Clinical Center for Aicardi-Goutieres Syndrome 4

Genetic Tests for Aicardi-Goutieres Syndrome 4

Genetic tests related to Aicardi-Goutieres Syndrome 4:

# Genetic test Affiliating Genes
1 Aicardi Goutieres Syndrome 4 29 RNASEH2A

Anatomical Context for Aicardi-Goutieres Syndrome 4

MalaCards organs/tissues related to Aicardi-Goutieres Syndrome 4:

41
Skin, Brain, Spinal Cord, Liver, Testes

Publications for Aicardi-Goutieres Syndrome 4

Articles related to Aicardi-Goutieres Syndrome 4:

# Title Authors Year
1
Extensive intracranial calcification of pseudo-TORCH syndrome with features of Dandy-Walker malformation. ( 28761539 )
2017
2
Human USP18 deficiency underlies type 1 interferonopathy leading to severe pseudo-TORCH syndrome. ( 27325888 )
2016
3
Anaesthetic Management of a Patient with Pseudo-TORCH Syndrome. ( 25207129 )
2013
4
Two brothers with findings resembling congenital intrauterine infection-like syndrome (pseudo-TORCH syndrome). ( 12833411 )
2003
5
Pseudo-TORCH syndrome or Baraitser-Reardon syndrome: diagnostic criteria. ( 11226724 )
2001

Variations for Aicardi-Goutieres Syndrome 4

UniProtKB/Swiss-Prot genetic disease variations for Aicardi-Goutieres Syndrome 4:

75
# Symbol AA change Variation ID SNP ID
1 RNASEH2A p.Gly37Ser VAR_027377 rs76857106
2 RNASEH2A p.Arg108Trp VAR_070625 rs76436818
3 RNASEH2A p.Arg186Trp VAR_070626 rs77103971
4 RNASEH2A p.Phe230Leu VAR_070628 rs79767407
5 RNASEH2A p.Arg235Gln VAR_070629 rs75718910
6 RNASEH2A p.Thr240Met VAR_070630 rs79843600
7 RNASEH2A p.Arg291His VAR_070632 rs75037667

ClinVar genetic disease variations for Aicardi-Goutieres Syndrome 4:

6
(show all 48)
# Gene Variation Type Significance SNP ID Assembly Location
1 RNASEH2A NM_006397.2(RNASEH2A): c.109G> A (p.Gly37Ser) single nucleotide variant Pathogenic rs76857106 GRCh37 Chromosome 19, 12917596: 12917596
2 RNASEH2A NM_006397.2(RNASEH2A): c.109G> A (p.Gly37Ser) single nucleotide variant Pathogenic rs76857106 GRCh38 Chromosome 19, 12806782: 12806782
3 RNASEH2A NM_006397.2(RNASEH2A): c.75C> T (p.Arg25=) single nucleotide variant Pathogenic rs397515479 GRCh37 Chromosome 19, 12917562: 12917562
4 RNASEH2A NM_006397.2(RNASEH2A): c.75C> T (p.Arg25=) single nucleotide variant Pathogenic rs397515479 GRCh38 Chromosome 19, 12806748: 12806748
5 RNASEH2A NM_006397.2(RNASEH2A): c.704G> A (p.Arg235Gln) single nucleotide variant Pathogenic rs75718910 GRCh37 Chromosome 19, 12923963: 12923963
6 RNASEH2A NM_006397.2(RNASEH2A): c.704G> A (p.Arg235Gln) single nucleotide variant Pathogenic rs75718910 GRCh38 Chromosome 19, 12813149: 12813149
7 RNASEH2A NM_006397.2(RNASEH2A): c.69G> A (p.Val23=) single nucleotide variant Pathogenic rs397515480 GRCh37 Chromosome 19, 12917556: 12917556
8 RNASEH2A NM_006397.2(RNASEH2A): c.69G> A (p.Val23=) single nucleotide variant Pathogenic rs397515480 GRCh38 Chromosome 19, 12806742: 12806742
9 RNASEH2A NM_006397.2(RNASEH2A): c.556C> T (p.Arg186Trp) single nucleotide variant Likely pathogenic rs77103971 GRCh37 Chromosome 19, 12921137: 12921137
10 RNASEH2A NM_006397.2(RNASEH2A): c.556C> T (p.Arg186Trp) single nucleotide variant Likely pathogenic rs77103971 GRCh38 Chromosome 19, 12810323: 12810323
11 RNASEH2A NM_006397.2(RNASEH2A): c.635A> T (p.Asn212Ile) single nucleotide variant Pathogenic rs377244188 GRCh37 Chromosome 19, 12921216: 12921216
12 RNASEH2A NM_006397.2(RNASEH2A): c.635A> T (p.Asn212Ile) single nucleotide variant Pathogenic rs377244188 GRCh38 Chromosome 19, 12810402: 12810402
13 RNASEH2A NM_006397.2(RNASEH2A): c.207_208insG (p.Thr70Aspfs) insertion Pathogenic rs77672568 GRCh38 Chromosome 19, 12807213: 12807213
14 RNASEH2A NM_006397.2(RNASEH2A): c.207_208insG (p.Thr70Aspfs) insertion Pathogenic rs77672568 GRCh37 Chromosome 19, 12918027: 12918027
15 RNASEH2A NM_006397.2(RNASEH2A): c.322C> T (p.Arg108Trp) single nucleotide variant Pathogenic rs76436818 GRCh37 Chromosome 19, 12918142: 12918142
16 RNASEH2A NM_006397.2(RNASEH2A): c.322C> T (p.Arg108Trp) single nucleotide variant Pathogenic rs76436818 GRCh38 Chromosome 19, 12807328: 12807328
17 RNASEH2A NM_006397.2(RNASEH2A): c.690C> A (p.Phe230Leu) single nucleotide variant Pathogenic rs79767407 GRCh38 Chromosome 19, 12813135: 12813135
18 RNASEH2A NM_006397.2(RNASEH2A): c.690C> A (p.Phe230Leu) single nucleotide variant Pathogenic rs79767407 GRCh37 Chromosome 19, 12923949: 12923949
19 RNASEH2A NM_006397.2(RNASEH2A): c.716_717dupGC (p.Thr240Alafs) duplication Pathogenic rs78705193 GRCh37 Chromosome 19, 12923975: 12923976
20 RNASEH2A NM_006397.2(RNASEH2A): c.716_717dupGC (p.Thr240Alafs) duplication Pathogenic rs78705193 GRCh38 Chromosome 19, 12813161: 12813162
21 RNASEH2A NM_006397.2(RNASEH2A): c.719C> T (p.Thr240Met) single nucleotide variant Pathogenic rs79843600 GRCh38 Chromosome 19, 12813164: 12813164
22 RNASEH2A NM_006397.2(RNASEH2A): c.719C> T (p.Thr240Met) single nucleotide variant Pathogenic rs79843600 GRCh37 Chromosome 19, 12923978: 12923978
23 RNASEH2A NM_006397.2(RNASEH2A): c.872G> A (p.Arg291His) single nucleotide variant Pathogenic rs75037667 GRCh37 Chromosome 19, 12924252: 12924252
24 RNASEH2A NM_006397.2(RNASEH2A): c.872G> A (p.Arg291His) single nucleotide variant Pathogenic rs75037667 GRCh38 Chromosome 19, 12813438: 12813438
25 RNASEH2A NM_006397.2(RNASEH2A): c.33A> G (p.Thr11=) single nucleotide variant Benign/Likely benign rs11554400 GRCh38 Chromosome 19, 12806706: 12806706
26 RNASEH2A NM_006397.2(RNASEH2A): c.33A> G (p.Thr11=) single nucleotide variant Benign/Likely benign rs11554400 GRCh37 Chromosome 19, 12917520: 12917520
27 RNASEH2A NM_006397.2(RNASEH2A): c.462G> A (p.Gln154=) single nucleotide variant Benign/Likely benign rs7257575 GRCh38 Chromosome 19, 12810121: 12810121
28 RNASEH2A NM_006397.2(RNASEH2A): c.462G> A (p.Gln154=) single nucleotide variant Benign/Likely benign rs7257575 GRCh37 Chromosome 19, 12920935: 12920935
29 RNASEH2A NM_006397.2(RNASEH2A): c.605T> C (p.Leu202Ser) single nucleotide variant Benign/Likely benign rs7247284 GRCh38 Chromosome 19, 12810372: 12810372
30 RNASEH2A NM_006397.2(RNASEH2A): c.605T> C (p.Leu202Ser) single nucleotide variant Benign/Likely benign rs7247284 GRCh37 Chromosome 19, 12921186: 12921186
31 RNASEH2A NM_006397.2(RNASEH2A): c.615T> A (p.Asp205Glu) single nucleotide variant Benign/Likely benign rs62619782 GRCh38 Chromosome 19, 12810382: 12810382
32 RNASEH2A NM_006397.2(RNASEH2A): c.615T> A (p.Asp205Glu) single nucleotide variant Benign/Likely benign rs62619782 GRCh37 Chromosome 19, 12921196: 12921196
33 RNASEH2A NM_006397.2(RNASEH2A): c.662A> G (p.Lys221Arg) single nucleotide variant Conflicting interpretations of pathogenicity rs143534021 GRCh38 Chromosome 19, 12813107: 12813107
34 RNASEH2A NM_006397.2(RNASEH2A): c.662A> G (p.Lys221Arg) single nucleotide variant Conflicting interpretations of pathogenicity rs143534021 GRCh37 Chromosome 19, 12923921: 12923921
35 RNASEH2A NM_006397.2(RNASEH2A): c.777C> T (p.Ser259=) single nucleotide variant Benign/Likely benign rs76634951 GRCh37 Chromosome 19, 12924157: 12924157
36 RNASEH2A NM_006397.2(RNASEH2A): c.777C> T (p.Ser259=) single nucleotide variant Benign/Likely benign rs76634951 GRCh38 Chromosome 19, 12813343: 12813343
37 RNASEH2A NM_006397.2(RNASEH2A): c.417C> T (p.Phe139=) single nucleotide variant Likely benign rs201413125 GRCh38 Chromosome 19, 12810076: 12810076
38 RNASEH2A NM_006397.2(RNASEH2A): c.417C> T (p.Phe139=) single nucleotide variant Likely benign rs201413125 GRCh37 Chromosome 19, 12920890: 12920890
39 RNASEH2A NM_006397.2(RNASEH2A): c.29A> G (p.Asn10Ser) single nucleotide variant Uncertain significance GRCh38 Chromosome 19, 12806702: 12806702
40 RNASEH2A NM_006397.2(RNASEH2A): c.29A> G (p.Asn10Ser) single nucleotide variant Uncertain significance GRCh37 Chromosome 19, 12917516: 12917516
41 RNASEH2A NM_006397.2(RNASEH2A): c.36C> T (p.Gly12=) single nucleotide variant Likely benign rs375139492 GRCh38 Chromosome 19, 12806709: 12806709
42 RNASEH2A NM_006397.2(RNASEH2A): c.36C> T (p.Gly12=) single nucleotide variant Likely benign rs375139492 GRCh37 Chromosome 19, 12917523: 12917523
43 RNASEH2A NM_006397.2(RNASEH2A): c.412-6T> G single nucleotide variant Benign rs192358167 GRCh38 Chromosome 19, 12810065: 12810065
44 RNASEH2A NM_006397.2(RNASEH2A): c.412-6T> G single nucleotide variant Benign rs192358167 GRCh37 Chromosome 19, 12920879: 12920879
45 RNASEH2A NM_006397.2(RNASEH2A): c.222C> T (p.Ser74=) single nucleotide variant Uncertain significance rs891089016 GRCh37 Chromosome 19, 12918042: 12918042
46 RNASEH2A NM_006397.2(RNASEH2A): c.222C> T (p.Ser74=) single nucleotide variant Uncertain significance rs891089016 GRCh38 Chromosome 19, 12807228: 12807228
47 RNASEH2A NM_006397.2(RNASEH2A): c.465A> G (p.Gln155=) single nucleotide variant Likely benign rs758492414 GRCh38 Chromosome 19, 12810124: 12810124
48 RNASEH2A NM_006397.2(RNASEH2A): c.465A> G (p.Gln155=) single nucleotide variant Likely benign rs758492414 GRCh37 Chromosome 19, 12920938: 12920938

Expression for Aicardi-Goutieres Syndrome 4

Search GEO for disease gene expression data for Aicardi-Goutieres Syndrome 4.

Pathways for Aicardi-Goutieres Syndrome 4

GO Terms for Aicardi-Goutieres Syndrome 4

Sources for Aicardi-Goutieres Syndrome 4

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