GRIDHH
MCID: GRW040
MIFTS: 22

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 74
Gridhh 57 74
Growth Delay-Intellectual Disability-Hepatopathy Syndrome 59

Characteristics:

OMIM:

57
Inheritance:
autosomal recessive

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


HPO:

32
growth retardation, impaired intellectual development, hypotonia, and hepatopathy:
Inheritance autosomal recessive inheritance
Onset and clinical course variable expressivity congenital onset


Classifications:



External Ids:

OMIM 57 617093
Orphanet 59 ORPHA541423

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)

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). Affiliated tissues include liver and skin, and related phenotypes are seizures and spasticity

UniProtKB/Swiss-Prot : 74 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:

32 (show all 17)
# Description HPO Frequency HPO Source Accession
1 seizures 32 occasional (7.5%) HP:0001250
2 spasticity 32 occasional (7.5%) HP:0001257
3 sensorineural hearing impairment 32 occasional (7.5%) HP:0000407
4 decreased liver function 32 occasional (7.5%) HP:0001410
5 hepatic steatosis 32 occasional (7.5%) HP:0001397
6 elevated hepatic transaminase 32 occasional (7.5%) HP:0002910
7 intellectual disability 32 HP:0001249
8 failure to thrive 32 HP:0001508
9 global developmental delay 32 HP:0001263
10 microcephaly 32 HP:0000252
11 generalized hypotonia 32 HP:0001290
12 intrauterine growth retardation 32 HP:0001511
13 postnatal growth retardation 32 HP:0008897
14 joint laxity 32 HP:0001388
15 hydronephrosis 32 HP:0000126
16 round face 32 HP:0000311
17 duplicated collecting system 32 HP:0000081

Symptoms via clinical synopsis from OMIM:

57
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

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:

41
Liver, Skin

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. 8 71
27891590 2017
2
Biallelic IARS Mutations Cause Growth Retardation with Prenatal Onset, Intellectual Disability, Muscular Hypotonia, and Infantile Hepatopathy. 8 71
27426735 2016

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

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

6
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 IARS1 NM_013417.3(IARS1): c.1667T> C (p.Phe556Ser) single nucleotide variant Pathogenic rs1554728327 9:95027244-95027244 9:92264962-92264962
2 IARS1 NM_013417.3(IARS1): c.2215C> T (p.Arg739Cys) single nucleotide variant Pathogenic rs747311061 9:95015658-95015658 9:92253376-92253376
3 IARS1 NM_013417.3(IARS1): c.1252C> T (p.Arg418Ter) single nucleotide variant Pathogenic rs764500338 9:95032219-95032219 9:92269937-92269937
4 IARS1 NM_013417.3(IARS1): c.3521T> A (p.Ile1174Asn) single nucleotide variant Pathogenic rs886037873 9:94985660-94985660 9:92223378-92223378
5 IARS1 NM_013417.3(IARS1): c.1310C> T (p.Pro437Leu) single nucleotide variant Pathogenic rs886037874 9:95030577-95030577 9:92268295-92268295
6 IARS1 NM_013417.3(IARS1): c.760C> T (p.Arg254Ter) single nucleotide variant Pathogenic rs886037875 9:95040554-95040554 9:92278272-92278272
7 IARS1 NM_013417.3(IARS1): c.1109T> G (p.Val370Gly) single nucleotide variant Pathogenic rs886037876 9:95033819-95033819 9:92271537-92271537
8 IARS1 NM_013417.3(IARS1): c.2974A> G (p.Asn992Asp) single nucleotide variant Pathogenic rs886037877 9:95005524-95005524 9:92243242-92243242
9 IARS1 NM_013417.3(IARS1): c.1358G> A (p.Arg453His) single nucleotide variant Uncertain significance 9:95030529-95030529 9:92268247-92268247

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

74
# 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,...

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
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 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
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