HSCR2
MCID: HRS036
MIFTS: 34

Hirschsprung Disease 2 (HSCR2)

Categories: Fetal diseases, Gastrointestinal diseases, Genetic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Hirschsprung Disease 2

MalaCards integrated aliases for Hirschsprung Disease 2:

Name: Hirschsprung Disease 2 57 74 29 55 6
Hirschsprung Disease, Susceptibility to, 2 57 13
Hscr2 57 74
Hirschsprung Disease, Type 2 40
Hirschsprung Disease Type 2 53
Aganglionic Megacolon 74
Hirschsprung Disease 72
Mgc 74

Characteristics:

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
penetrance of phenotype may be dosage sensitive


HPO:

32

Classifications:



External Ids:

MeSH 44 D006627
MedGen 42 C1838564
UMLS 72 C0019569

Summaries for Hirschsprung Disease 2

OMIM : 57 The disorder described by Hirschsprung (1888) and known as Hirschsprung disease or aganglionic megacolon is characterized by congenital absence of intrinsic ganglion cells in the myenteric (Auerbach) and submucosal (Meissner) plexuses of the gastrointestinal tract. Patients are diagnosed with the short-segment form (S-HSCR, approximately 80% of cases) when the aganglionic segment does not extend beyond the upper sigmoid, and with the long-segment form (L-HSCR) when aganglionosis extends proximal to the sigmoid. Total colonic aganglionosis and total intestinal HSCR also occur (Amiel et al., 2008). Isolated HSCR appears to be of complex nonmendelian inheritance with low sex-dependent penetrance and variable expression according to the length of the aganglionic segment, suggestive of the involvement of one or more genes with low penetrance (Amiel et al., 2008). For a general description and a discussion of genetic heterogeneity of Hirschsprung disease (HSCR), see 142623. (600155)

MalaCards based summary : Hirschsprung Disease 2, also known as hirschsprung disease, susceptibility to, 2, is related to hirschsprung disease 1 and ifap syndrome with or without bresheck syndrome. An important gene associated with Hirschsprung Disease 2 is EDNRB (Endothelin Receptor Type B). The drugs Vaccines and Cola have been mentioned in the context of this disorder. Affiliated tissues include colon and heart, and related phenotype is aganglionic megacolon.

UniProtKB/Swiss-Prot : 74 Hirschsprung disease 2: A disorder of neural crest development characterized by absence of enteric ganglia along a variable length of the intestine. It is the most common cause of congenital intestinal obstruction. Early symptoms range from complete acute neonatal obstruction, characterized by vomiting, abdominal distention and failure to pass stool, to chronic constipation in the older child.

Related Diseases for Hirschsprung Disease 2

Diseases in the Hirschsprung Disease 1 family:

Hirschsprung Disease 2 Hirschsprung Disease 5
Hirschsprung Disease 6 Hirschsprung Disease 7
Hirschsprung Disease 8 Hirschsprung Disease 9
Hirschsprung Disease 3 Hirschsprung Disease 4

Diseases related to Hirschsprung Disease 2 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 46)
# Related Disease Score Top Affiliating Genes
1 hirschsprung disease 1 12.6
2 ifap syndrome with or without bresheck syndrome 11.4
3 hirschsprung disease 5 11.4
4 hirschsprung disease 6 11.4
5 hirschsprung disease 7 11.4
6 hirschsprung disease 8 11.4
7 hirschsprung disease 9 11.4
8 hirschsprung disease 3 11.4
9 hirschsprung disease 4 11.4
10 waardenburg's syndrome 11.4
11 ichthyosis follicularis atrichia photophobia syndrome 11.4
12 megacolon 11.1
13 intestinal obstruction 10.6
14 gastric cancer 10.5
15 diarrhea 10.4
16 constipation 10.4
17 myeloma, multiple 10.3
18 adenocarcinoma 10.3
19 gastric adenocarcinoma 10.3
20 cleft palate, isolated 10.2
21 pheochromocytoma 10.2
22 down syndrome 10.2
23 enterocolitis 10.2
24 congenital hypothyroidism 10.2
25 adrenal gland pheochromocytoma 10.2
26 colitis 10.2
27 renal hypoplasia 10.2
28 pyloric stenosis 10.2
29 hypothyroidism 10.2
30 achalasia 10.2
31 neurofibroma 10.2
32 ring chromosome 10 10.2
33 hypotonia 10.2
34 ring chromosome 10.2
35 polykaryocytosis inducer 10.1
36 ocular motor apraxia 10.1
37 primary hyperparathyroidism 10.1
38 neutropenia 10.1
39 hyperparathyroidism 10.1
40 peripheral nervous system disease 10.1
41 neuropathy 10.1
42 stomatitis 10.1
43 traumatic brain injury 10.1
44 abcd syndrome 9.5 EDNRB-AS1 EDNRB
45 waardenburg syndrome, type 4a 9.4 EDNRB-AS1 EDNRB
46 waardenburg syndrome, type 2a 9.2 EDNRB-AS1 EDNRB

Graphical network of the top 20 diseases related to Hirschsprung Disease 2:



Diseases related to Hirschsprung Disease 2

Symptoms & Phenotypes for Hirschsprung Disease 2

Human phenotypes related to Hirschsprung Disease 2:

32
# Description HPO Frequency HPO Source Accession
1 aganglionic megacolon 32 HP:0002251

Symptoms via clinical synopsis from OMIM:

57
Abdomen Gastrointestinal:
hirschsprung disease
aganglionosis (sometimes confined to descending or rectosigmoid colon)

Clinical features from OMIM:

600155

Drugs & Therapeutics for Hirschsprung Disease 2

Drugs for Hirschsprung Disease 2 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 12)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1 Vaccines Phase 4
2 Cola Phase 3
3
Mineral oil Approved, Vet_approved 8042-47-5
4
Lactulose Approved 4618-18-2 11333
5
tannic acid Approved 1401-55-4
6
Benzocaine Approved, Investigational 94-09-7, 1994-09-7 2337
7
Metronidazole Approved 443-48-1 4173
8 Gastrointestinal Agents
9 Dermatologic Agents
10 Emollients
11 Anesthetics
12 Pharmaceutical Solutions

Interventional clinical trials:

(show all 27)
# Name Status NCT ID Phase Drugs
1 Immunodeficiency in Cartilage-hair Hypoplasia: Correlation With Pulmonary Disease, Infections and Malignancy Unknown status NCT02383797 Phase 4
2 Probiotics for Prophylaxis of Postoperative Hirschsprungs Associated Enterocolitis Recruiting NCT02343562 Phase 4
3 Effects of Butyrate Enemas on Postoperative Intestinal Mobility Disorders in Hirschsprung's Not yet recruiting NCT03660176 Phase 3 butyrate enemas + routine management
4 Endoscopic Mucosal Resection for the Diagnosis of a-Ganglionosis, a Controlled Prospective Trial Unknown status NCT00671684 Phase 1, Phase 2
5 Probiotic Prophylaxis of Hirschprung's Disease Associated Enterocolitis (HAEC) Completed NCT00630838 Phase 2 VSL#3;Placebo
6 Comparison of Circular(Soave) and Heart-shaped Anastomosis in Hirschsprung's Disease: A Prospective Multicenter Randomized Controlled Trial Unknown status NCT02234219 Probiotics
7 Fast-track Surgery in the Treatment of Hirschsprung's Disease Unknown status NCT02350088 probiotics;placebo
8 Efficacy and Accuracy of a New Diagnostic Scoring System to Differentiate Hirschsprung Disease From Hirschsprung Disease Allied Disorders in the Patients With Suspected Intestinal Dysganglinosis: a Prospective Study Unknown status NCT02216994 high dose lactulose;paraffin oil
9 The Elactrophysiological Response of the Colon, in Normal Bowel, and Large Bowel Lacking Ganglia in Children With Suspected Hirschsprungs Disease. Unknown status NCT02342457
10 A Prospective, Randomized Controlled Trial of Conservative Versus Surgery Treatment of Normal and Short-segment Hirschsprung Disease for Infants Completed NCT01985646 Early Phase 1 oral probiotic
11 MICROPRUNG : Intestinal Microbiota Analysis in Patients With or Without Hirschsprung's Associated EnteroColitis Completed NCT02857205
12 A Prospective Multicenter Randomized Controlled Trial on Probiotics in Preventing Hirschsprung's Disease Associated Entercolitis Completed NCT01934959 Early Phase 1 Bifico
13 Endoscopic Mucosal Resection for the Diagnosis of a-Ganglionosis, a Controlled Prospective Trial (EDGE Trial) Completed NCT01515501
14 3D High Resolution Anorectal Manometry in Children After Surgery for Anorectal Disorders Completed NCT02296008
15 Randomized Controlled Trial: Rapid Learning Healthcare System in Pediatric Surgery Completed NCT03131180
16 Identification of Genetic, Immunologic and Microbial Markers of Hirschsprung Associated Enterocolitis in Children With Hirschsprung Disease Recruiting NCT02193685
17 Genetic Analysis of Hirschsprung Disease Recruiting NCT00478712
18 Genetics of Hirschsprung's Disease - Can Genetic Mosaicism Due to Early Somatic Mutations, Explain Disease Development? Recruiting NCT01927809
19 A Prospective Multi-center Randomized Controlled Clinical Trials of Enhanced Recovery After Surgery in Hirschsprung Disease. Recruiting NCT02776176
20 Neuropsychological Development and Functional Outcome Sin Children With Hirschsprung Disease at School Age - Hirschsprung Recruiting NCT03406741
21 Management and Outcomes of Congenital Anomalies in Low-, Middle- and High-Income Countries: A Multi-Centre, International, Prospective Cohort Study Recruiting NCT03666767
22 The Enteric Nervous System as Modulator of Mucosal Immune Cells Recruiting NCT03617640
23 Neurocognitive Outcome as a Metric for Evaluating Therapeutic Intervention and Treatment Mechanisms in Congenital Central Hypoventilation Syndrome (CCHS): A Multi-Site Study Using The NIH Toolbox Recruiting NCT03568669
24 International Congenital Central Hypoventilation Syndrome (CCHS) REDCap Registry Recruiting NCT03088020
25 Prospective Evaluation of the Efficacy and Safety of Submucosal Endoscopy Enrolling by invitation NCT03626350
26 Laparoscopic Assisted Pull-through Versus Other Surgical Procedures for Treatment of Hirschsprung Disease. Not yet recruiting NCT03269812
27 The Role of Indocyanine Green Angiography Fluorescence on Intestinal Resections in Pediatric Surgery. Not yet recruiting NCT04020939 Indocyanine Green

Search NIH Clinical Center for Hirschsprung Disease 2

Genetic Tests for Hirschsprung Disease 2

Genetic tests related to Hirschsprung Disease 2:

# Genetic test Affiliating Genes
1 Hirschsprung Disease 2 29 EDNRB

Anatomical Context for Hirschsprung Disease 2

MalaCards organs/tissues related to Hirschsprung Disease 2:

41
Colon, Heart

Publications for Hirschsprung Disease 2

Articles related to Hirschsprung Disease 2:

(show all 24)
# Title Authors PMID Year
1
A missense mutation of the endothelin-B receptor gene in multigenic Hirschsprung's disease. 9 38 8 71
8001158 1994
2
Hirschsprung disease in an infant with a contiguous gene syndrome of chromosome 13. 9 38 8
11484199 2001
3
Analysis of protein-coding genetic variation in 60,706 humans. 71
27535533 2016
4
New roles of EDNRB and EDN3 in the pathogenesis of Hirschsprung disease. 71
20009762 2010
5
Hirschsprung disease, associated syndromes and genetics: a review. 8
17965226 2008
6
Hirschsprung Disease Overview 71
20301612 2002
7
Double heterozygosity for a RET substitution interfering with splicing and an EDNRB missense mutation in Hirschsprung disease. 71
10090908 1999
8
Phenotypic variation in a family with mutations in two Hirschsprung-related genes (RET and endothelin receptor B). 71
9760196 1998
9
A missense mutation in the endothelin-B receptor gene is associated with Lethal White Foal Syndrome: an equine version of Hirschsprung disease. 8
9585428 1998
10
A dinucleotide mutation in the endothelin-B receptor gene is associated with lethal white foal syndrome (LWFS); a horse variant of Hirschsprung disease. 8
9580670 1998
11
Endothelin receptor B polymorphism associated with lethal white foal syndrome in horses. 8
9530628 1998
12
Mutations in Hirschsprung disease: when does a mutation contribute to the phenotype. 71
9359036 1997
13
Novel mutations of the endothelin-B receptor gene in isolated patients with Hirschsprung's disease. 71
8852658 1996
14
Targeted and natural (piebald-lethal) mutations of endothelin-B receptor gene produce megacolon associated with spotted coat color in mice. 8
8001159 1994
15
Identity-by-descent and association mapping of a recessive gene for Hirschsprung disease on human chromosome 13q22. 8
7987295 1994
16
A case of Hirschsprung disease with a chromosome 13 microdeletion, del(13)(q32.3q33.2): potential mapping of one disease locus. 8
1937482 1991
17
A genetic study of Hirschsprung disease. 8
2309705 1990
18
Association of 13q deletion and Hirschsprung's disease. 8
2614805 1989
19
Interstitial deletion of distal 13q associated with Hirschsprung's disease. 8
2918536 1989
20
Separation of retinoblastoma and esterase D loci in a patient with sporadic retinoblastoma and del(13)(q14.1q22.3). 8
6500578 1984
21
Hirschsprung's disease in a kindred: a possible clue to the genetics of the disease. 8
6217309 1982
22
Ileocolonic aganglionosis in white progeny of overo spotted horses. 8
7056678 1982
23
Ten-Year Experience With Bowel Transplantation at Seoul St. Mary's Hospital. 38
27109981 2016
24
[The efficacy of the Childs-Phillips mesenteric plication in intestinal obstruction]. 38
2073471 1990

Variations for Hirschsprung Disease 2

ClinVar genetic disease variations for Hirschsprung Disease 2:

6
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 EDNRB NM_000115.5(EDNRB): c.828G> T (p.Trp276Cys) single nucleotide variant Pathogenic rs104894387 13:78475316-78475316 13:77901181-77901181
2 EDNRB NM_000115.5(EDNRB): c.824G> A (p.Trp275Ter) single nucleotide variant risk factor rs104894389 13:78475320-78475320 13:77901185-77901185
3 EDNRB NM_000115.5(EDNRB): c.877dup (p.Tyr293fs) duplication risk factor 13:78475267-78475267 13:77901132-77901132
4 EDNRB NM_000115.5(EDNRB): c.-51-949A> T single nucleotide variant risk factor rs267606780 13:78493708-78493708 13:77919573-77919573
5 EDNRB NM_000115.5(EDNRB): c.-26G> A single nucleotide variant Conflicting interpretations of pathogenicity rs2070591 13:78492734-78492734 13:77918599-77918599
6 EDNRB NM_000115.5(EDNRB): c.169G> A (p.Gly57Ser) single nucleotide variant Conflicting interpretations of pathogenicity rs1801710 13:78492540-78492540 13:77918405-77918405
7 EDNRB NM_000115.5(EDNRB): c.914G> A (p.Ser305Asn) single nucleotide variant Benign/Likely benign rs5352 13:78475230-78475230 13:77901095-77901095
8 EDNRB NM_000115.5(EDNRB): c.778G> T (p.Val260Phe) single nucleotide variant not provided 13:78477314-78477314 13:77903179-77903179

UniProtKB/Swiss-Prot genetic disease variations for Hirschsprung Disease 2:

74
# Symbol AA change Variation ID SNP ID
1 EDNRB p.Trp276Cys VAR_003471 rs104894387
2 EDNRB p.Arg319Trp VAR_003473 rs200363611
3 EDNRB p.Met374Ile VAR_003474
4 EDNRB p.Pro383Leu VAR_003475

Expression for Hirschsprung Disease 2

Search GEO for disease gene expression data for Hirschsprung Disease 2.

Pathways for Hirschsprung Disease 2

GO Terms for Hirschsprung Disease 2

Sources for Hirschsprung Disease 2

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
Content
Loading form....