GRIDHH
MCID: GRW040
MIFTS: 25

Growth Retardation, Impaired Intellectual Development, Hypotonia, and Hepatopathy (GRIDHH)

Categories: Genetic diseases, Liver diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Growth Retardation, Impaired Intellectual Development, Hypotonia,...

MalaCards integrated aliases for Growth Retardation, Impaired Intellectual Development, Hypotonia, and Hepatopathy:

Name: Growth Retardation, Impaired Intellectual Development, Hypotonia, and Hepatopathy 57 73 36 6
Gridhh 57 73
Growth Delay-Intellectual Disability-Hepatopathy Syndrome 58

Characteristics:

OMIM®:

57 (Updated 05-Mar-2021)
Inheritance:
autosomal recessive

Miscellaneous:
variable severity
onset at birth
four unrelated patients have been reported (last curated august 2018)


HPO:

31
growth retardation, impaired intellectual development, hypotonia, and hepatopathy:
Inheritance autosomal recessive inheritance
Onset and clinical course variable expressivity congenital onset


Classifications:

Orphanet: 58  
Rare neurological diseases
Rare hepatic diseases


Summaries for Growth Retardation, Impaired Intellectual Development, Hypotonia,...

OMIM® : 57 GRIDHH is an autosomal recessive multisystem disorder characterized by poor overall growth, impaired intellectual development, hypotonia, and variable liver dysfunction. Additional features, such as seizures and hearing loss, may also be present (summary by Kopajtich et al., 2016). (617093) (Updated 05-Mar-2021)

MalaCards based summary : Growth Retardation, Impaired Intellectual Development, Hypotonia, and Hepatopathy, is also known as gridhh. An important gene associated with Growth Retardation, Impaired Intellectual Development, Hypotonia, and Hepatopathy is IARS1 (Isoleucyl-TRNA Synthetase 1), and among its related pathways/superpathways is Aminoacyl-tRNA biosynthesis. Affiliated tissues include liver and brain, and related phenotypes are intellectual disability and intrauterine growth retardation

KEGG : 36 Growth retardation, impaired intellectual development, hypotonia, and hepatopathy (GRIDHH) is a prenatal onset syndrome caused by bi-allelic mutations in cytosolic isoleucyl-tRNA synthetase (IARS).

UniProtKB/Swiss-Prot : 73 Growth retardation, impaired intellectual development, hypotonia, and hepatopathy: An autosomal recessive disorder characterized by severe growth retardation with prenatal onset, intellectual disability, muscular hypotonia, and hepatic dysfunction.

Related Diseases for Growth Retardation, Impaired Intellectual Development, Hypotonia,...

Symptoms & Phenotypes for Growth Retardation, Impaired Intellectual Development, Hypotonia,...

Human phenotypes related to Growth Retardation, Impaired Intellectual Development, Hypotonia, and Hepatopathy:

58 31 (show all 42)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 intellectual disability 58 31 hallmark (90%) Very frequent (99-80%) HP:0001249
2 intrauterine growth retardation 58 31 hallmark (90%) Very frequent (99-80%) HP:0001511
3 elevated hepatic transaminase 58 31 occasional (7.5%) Very frequent (99-80%) HP:0002910
4 psychomotor retardation 58 31 hallmark (90%) Very frequent (99-80%) HP:0025356
5 decreased serum zinc 58 31 hallmark (90%) Very frequent (99-80%) HP:0031831
6 absent speech 58 31 frequent (33%) Frequent (79-30%) HP:0001344
7 hepatic steatosis 58 31 occasional (7.5%) Frequent (79-30%) HP:0001397
8 hepatic fibrosis 58 31 frequent (33%) Frequent (79-30%) HP:0001395
9 cholestasis 58 31 frequent (33%) Frequent (79-30%) HP:0001396
10 feeding difficulties 58 31 frequent (33%) Frequent (79-30%) HP:0011968
11 recurrent infections 58 31 frequent (33%) Frequent (79-30%) HP:0002719
12 hypotonia 31 frequent (33%) HP:0001252
13 spasticity 58 31 occasional (7.5%) Occasional (29-5%) HP:0001257
14 diabetes mellitus 58 31 occasional (7.5%) Occasional (29-5%) HP:0000819
15 microcephaly 58 31 occasional (7.5%) Occasional (29-5%) HP:0000252
16 sensorineural hearing impairment 58 31 occasional (7.5%) Occasional (29-5%) HP:0000407
17 full cheeks 58 31 occasional (7.5%) Occasional (29-5%) HP:0000293
18 joint laxity 58 31 occasional (7.5%) Occasional (29-5%) HP:0001388
19 hydronephrosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0000126
20 hepatic failure 58 31 occasional (7.5%) Occasional (29-5%) HP:0001399
21 round face 58 31 occasional (7.5%) Occasional (29-5%) HP:0000311
22 hyperextensible skin 58 31 occasional (7.5%) Occasional (29-5%) HP:0000974
23 oligohydramnios 58 31 occasional (7.5%) Occasional (29-5%) HP:0001562
24 mild global developmental delay 58 31 occasional (7.5%) Occasional (29-5%) HP:0011342
25 autistic behavior 58 31 occasional (7.5%) Occasional (29-5%) HP:0000729
26 brain imaging abnormality 58 31 occasional (7.5%) Occasional (29-5%) HP:0410263
27 hepatosplenomegaly 58 31 occasional (7.5%) Occasional (29-5%) HP:0001433
28 duplicated collecting system 58 31 occasional (7.5%) Occasional (29-5%) HP:0000081
29 dermal translucency 58 31 occasional (7.5%) Occasional (29-5%) HP:0010648
30 esophagitis 58 31 occasional (7.5%) Occasional (29-5%) HP:0100633
31 soft, doughy skin 58 31 occasional (7.5%) Occasional (29-5%) HP:0001027
32 abnormality of vitamin d metabolism 58 31 occasional (7.5%) Occasional (29-5%) HP:0100511
33 drumstick terminal phalanges 58 31 occasional (7.5%) Occasional (29-5%) HP:0006129
34 decreased liver function 31 occasional (7.5%) HP:0001410
35 seizure 31 occasional (7.5%) HP:0001250
36 seizures 58 Occasional (29-5%)
37 failure to thrive 31 HP:0001508
38 muscular hypotonia 58 Frequent (79-30%)
39 global developmental delay 31 HP:0001263
40 growth delay 58 Very frequent (99-80%)
41 postnatal growth retardation 31 HP:0008897
42 generalized hypotonia 31 HP:0001290

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Mar-2021)
Growth Other:
failure to thrive
intrauterine growth retardation
postnatal growth retardation

Genitourinary Kidneys:
hydronephrosis
duplicated collecting system

Muscle Soft Tissue:
hypotonia

Abdomen Liver:
liver dysfunction (in some patients)
steatosis (in some patients)
fibrosis (in some patients)

Head And Neck Ears:
sensorineural hearing loss (1 patient)

Abdomen External Features:
increased fat in genitalia area

Endocrine Features:
growth hormone resistance

Skeletal:
joint laxity

Head And Neck Face:
round face

Neurologic Central Nervous System:
delayed psychomotor development
seizures (1 patient)
spasticity (1 patient)
intellectual disability, variable severity

Laboratory Abnormalities:
abnormal liver enzymes (in some patients)
zinc deficiency
mitochondrial complex i deficiency in some tissues

Head And Neck Head:
microcephaly (-3 to -5 sd)

Skin Nails Hair Skin:
soft translucent hyperelastic skin

Clinical features from OMIM®:

617093 (Updated 05-Mar-2021)

Drugs & Therapeutics for Growth Retardation, Impaired Intellectual Development, Hypotonia,...

Search Clinical Trials , NIH Clinical Center for Growth Retardation, Impaired Intellectual Development, Hypotonia, and Hepatopathy

Genetic Tests for Growth Retardation, Impaired Intellectual Development, Hypotonia,...

Anatomical Context for Growth Retardation, Impaired Intellectual Development, Hypotonia,...

MalaCards organs/tissues related to Growth Retardation, Impaired Intellectual Development, Hypotonia, and Hepatopathy:

40
Liver, Brain

Publications for Growth Retardation, Impaired Intellectual Development, Hypotonia,...

Articles related to Growth Retardation, Impaired Intellectual Development, Hypotonia, and Hepatopathy:

# Title Authors PMID Year
1
Bi-allelic IARS mutations in a child with intra-uterine growth retardation, neonatal cholestasis, and mild developmental delay. 6 57
27891590 2017
2
Biallelic IARS Mutations Cause Growth Retardation with Prenatal Onset, Intellectual Disability, Muscular Hypotonia, and Infantile Hepatopathy. 57 6
27426735 2016

Variations for Growth Retardation, Impaired Intellectual Development, Hypotonia,...

ClinVar genetic disease variations for Growth Retardation, Impaired Intellectual Development, Hypotonia, and Hepatopathy:

6 (show all 11)
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 IARS1 NM_002161.6(IARS1):c.1252C>T (p.Arg418Ter) SNV Pathogenic 253317 rs764500338 9:95032219-95032219 9:92269937-92269937
2 IARS1 NM_002161.6(IARS1):c.760C>T (p.Arg254Ter) SNV Pathogenic 253320 rs886037875 9:95040554-95040554 9:92278272-92278272
3 IARS1 NM_002161.6(IARS1):c.1109T>G (p.Val370Gly) SNV Pathogenic 253321 rs886037876 9:95033819-95033819 9:92271537-92271537
4 IARS1 NM_002161.6(IARS1):c.3521T>A (p.Ile1174Asn) SNV Pathogenic 253318 rs886037873 9:94985660-94985660 9:92223378-92223378
5 IARS1 NM_002161.6(IARS1):c.1310C>T (p.Pro437Leu) SNV Pathogenic 253319 rs886037874 9:95030577-95030577 9:92268295-92268295
6 IARS1 NM_002161.6(IARS1):c.2974A>G (p.Asn992Asp) SNV Pathogenic 253322 rs886037877 9:95005524-95005524 9:92243242-92243242
7 IARS1 NM_002161.6(IARS1):c.1667T>C (p.Phe556Ser) SNV Pathogenic 559509 rs1554728327 9:95027244-95027244 9:92264962-92264962
8 IARS1 NM_002161.6(IARS1):c.2215C>T (p.Arg739Cys) SNV Pathogenic 559510 rs747311061 9:95015658-95015658 9:92253376-92253376
9 IARS1 NM_002161.5(IARS1):c.1358G>A (p.Arg453His) SNV Uncertain significance 638353 rs570962385 9:95030529-95030529 9:92268247-92268247
10 IARS1 NM_002161.6(IARS1):c.226G>A (p.Gly76Arg) SNV Uncertain significance 828038 rs372859203 9:95050458-95050458 9:92288176-92288176
11 IARS1 NM_002161.6(IARS1):c.1622C>T (p.Pro541Leu) SNV Uncertain significance 828039 rs1286974333 9:95027289-95027289 9:92265007-92265007

UniProtKB/Swiss-Prot genetic disease variations for Growth Retardation, Impaired Intellectual Development, Hypotonia, and Hepatopathy:

73
# Symbol AA change Variation ID SNP ID
1 IARS1 p.Val370Gly VAR_077055 rs886037876
2 IARS1 p.Pro437Leu VAR_077056 rs886037874
3 IARS1 p.Asn992Asp VAR_077057 rs886037877
4 IARS1 p.Ile1174Asn VAR_077058 rs886037873

Expression for Growth Retardation, Impaired Intellectual Development, Hypotonia,...

Search GEO for disease gene expression data for Growth Retardation, Impaired Intellectual Development, Hypotonia, and Hepatopathy.

Pathways for Growth Retardation, Impaired Intellectual Development, Hypotonia,...

Pathways related to Growth Retardation, Impaired Intellectual Development, Hypotonia, and Hepatopathy according to KEGG:

36
# Name Kegg Source Accession
1 Aminoacyl-tRNA biosynthesis hsa00970

GO Terms for Growth Retardation, Impaired Intellectual Development, Hypotonia,...

Sources for Growth Retardation, Impaired Intellectual Development, Hypotonia,...

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Mar-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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