GRIDHH
MCID: GRW040
MIFTS: 23

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 56 73
Gridhh 56 73
Growth Delay-Intellectual Disability-Hepatopathy Syndrome 58

Characteristics:

OMIM:

56
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 : 56 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 : 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:

31 (show all 17)
# Description HPO Frequency HPO Source Accession
1 seizures 31 occasional (7.5%) HP:0001250
2 spasticity 31 occasional (7.5%) HP:0001257
3 sensorineural hearing impairment 31 occasional (7.5%) HP:0000407
4 decreased liver function 31 occasional (7.5%) HP:0001410
5 hepatic steatosis 31 occasional (7.5%) HP:0001397
6 elevated hepatic transaminase 31 occasional (7.5%) HP:0002910
7 intellectual disability 31 HP:0001249
8 failure to thrive 31 HP:0001508
9 global developmental delay 31 HP:0001263
10 intrauterine growth retardation 31 HP:0001511
11 microcephaly 31 HP:0000252
12 generalized hypotonia 31 HP:0001290
13 postnatal growth retardation 31 HP:0008897
14 joint laxity 31 HP:0001388
15 hydronephrosis 31 HP:0000126
16 round face 31 HP:0000311
17 duplicated collecting system 31 HP:0000081

Symptoms via clinical synopsis from OMIM:

56
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:

40
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. 56 6
27891590 2017
2
Biallelic IARS Mutations Cause Growth Retardation with Prenatal Onset, Intellectual Disability, Muscular Hypotonia, and Infantile Hepatopathy. 6 56
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 Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 IARS1 NM_002161.5(IARS1):c.1252C>T (p.Arg418Ter)SNV Pathogenic 253317 rs764500338 9:95032219-95032219 9:92269937-92269937
2 IARS1 NM_002161.5(IARS1):c.3521T>A (p.Ile1174Asn)SNV Pathogenic 253318 rs886037873 9:94985660-94985660 9:92223378-92223378
3 IARS1 NM_002161.5(IARS1):c.1310C>T (p.Pro437Leu)SNV Pathogenic 253319 rs886037874 9:95030577-95030577 9:92268295-92268295
4 IARS1 NM_002161.5(IARS1):c.760C>T (p.Arg254Ter)SNV Pathogenic 253320 rs886037875 9:95040554-95040554 9:92278272-92278272
5 IARS1 NM_002161.5(IARS1):c.1109T>G (p.Val370Gly)SNV Pathogenic 253321 rs886037876 9:95033819-95033819 9:92271537-92271537
6 IARS1 NM_002161.5(IARS1):c.2974A>G (p.Asn992Asp)SNV Pathogenic 253322 rs886037877 9:95005524-95005524 9:92243242-92243242
7 IARS1 NM_002161.5(IARS1):c.1667T>C (p.Phe556Ser)SNV Pathogenic 559509 rs1554728327 9:95027244-95027244 9:92264962-92264962
8 IARS1 NM_002161.5(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 9:95030529-95030529 9:92268247-92268247

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,...

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 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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