Growth Retardation, Impaired Intellectual Development, Hypotonia, and Hepatopathy disease: Malacards - Research Articles, Drugs, Genes, Clinical Trials

GRIDHH MCID: GRW040 MIFTS: 25	Growth Retardation, Impaired Intellectual Development, Hypotonia, and Hepatopathy (GRIDHH) Categories: Genetic diseases, Liver diseases, Neuronal diseases, Rare diseases
Genes Variations Tissues Publications Pathways Symptoms & Phenotypes Expand all tables

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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:

MalaCards categories:
Global: Genetic diseases Rare diseases
Anatomical: Neuronal diseases Liver diseases

See all MalaCards categories (disease lists)

Orphanet: ⁵⁸

Rare neurological diseases

Rare hepatic diseases

External Ids:

OMIM® ⁵⁷ 617093

KEGG ³⁶ H02437

MeSH ⁴⁴ D006130 D008107 D008607 more

Orphanet ⁵⁸ ORPHA541423

MedGen ⁴¹ C4310720 CN238100

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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.

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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)

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

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

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

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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

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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	Orenstein N...Muenke M	27891590	2017
2	Biallelic IARS Mutations Cause Growth Retardation with Prenatal Onset, Intellectual Disability, Muscular Hypotonia, and Infantile Hepatopathy. ⁵⁷ ⁶	Kopajtich R...Staufner C	27426735	2016

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

Genes related to Growth Retardation, Impaired Intellectual Development, Hypotonia, and Hepatopathy (1 elite genes):

- Elite gene

- Cancer Census gene in COSMIC

#	Symbol	Description	Category	Score	Evidence	PubMed IDs
1	IARS1	Isoleucyl-TRNA Synthetase 1	Protein Coding	1568.63	Molecular basis known ⁵⁷ Pathogenic ⁶ Causative germline mutation ⁵⁸ Causative variation ⁷³ GeneCards inferred via : Disorders Variants (show sections)	27426735

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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

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

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

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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

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

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

¹ BioSystems

² BitterDB

³ CDC

⁴ Cell Signaling Technology

⁵ ClinicalTrials

⁶ ClinVar

⁷ CNVD

⁸ Cochrane Library

⁹ Cosmic

¹⁰ dbSNP

¹¹ DGIdb

¹² Disease Ontology

¹³ diseasecard

¹⁴ DiseaseEnhancer

¹⁵ DISEASES

¹⁶ DrugBank

¹⁷ EFO

¹⁸ ExPASy

¹⁹ FMA

²⁰ GARD

²¹ GeneAnalytics

²² GeneCards

²³ GeneGo (Thomson Reuters)

²⁴ GeneHancer via GeneCards

²⁵ GeneReviews

²⁶ GenomeRNAi

²⁷ GEO DataSets

²⁸ GO

²⁹ GTR

³⁰ HMDB

³¹ HPO

³² ICD10

³³ ICD10 via Orphanet

³⁴ ICD9CM

³⁵ IUPHAR

³⁶ KEGG

³⁷ LifeMap

³⁸ LncRNADisease

³⁹ LOVD

⁴⁰ MalaCards

⁴¹ MedGen

⁴² MedlinePlus

⁴³ MedlinePlus Genetics

⁴⁴ MeSH

⁴⁵ MESH via Orphanet

⁴⁶ MGI

⁴⁷ miR2Disease

⁴⁸ NCBI Bookshelf

⁴⁹ NCI

⁵⁰ NCIt

⁵¹ NDF-RT

⁵² NIH Clinical Center

⁵³ NINDS

⁵⁴ Novoseek

⁵⁵ Novus Biologicals

⁵⁶ OMIM via Orphanet

⁵⁷ OMIM® (Updated 05-Mar-2021)

⁵⁸ Orphanet

⁵⁹ PathCards

⁶⁰ PharmGKB

⁶¹ PubMed

⁶² PubMed Health

⁶³ QIAGEN

⁶⁴ R&D Systems

⁶⁵ Reactome

⁶⁶ Sino Biological

⁶⁷ SNOMED-CT

⁶⁸ SNOMED-CT via HPO

⁶⁹ TGDB

⁷⁰ Tocris

⁷¹ UMLS

⁷² UMLS via Orphanet

⁷³ UniProtKB/Swiss-Prot

⁷⁴ Wikipedia

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

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

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

Characteristics:

OMIM®:

HPO:

Classifications:

External Ids:

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

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:

Symptoms via clinical synopsis from OMIM®:

Clinical features from OMIM®:

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

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:

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

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

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

Genes related to Growth Retardation, Impaired Intellectual Development, Hypotonia, and Hepatopathy (1 elite genes):

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

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

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

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

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

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

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

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