MCID: JVN012
MIFTS: 26

Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia Syndrome

Categories: Genetic diseases

Aliases & Classifications for Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia...

MalaCards integrated aliases for Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia Syndrome:

Name: Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia Syndrome 53 71 28 13 69
Polyposis, Generalized Juvenile, with Pulmonary Arteriovenous Malformation 53
Telangiectasia, Hereditary Hemorrhagic, with Juvenile Polyposis Coli 53
Juvenile Polyposis with Hereditary Hemorrhagic Telangiectasia 53
Jp/hht Syndrome 53
Jps/hht 53
Jp/hht 71
Jpht 53

Characteristics:

OMIM:

53
Inheritance:
autosomal dominant

Miscellaneous:
onset usually in childhood
arteriovenous malformations can occur throughout the body


HPO:

31
juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome:
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia...

UniProtKB/Swiss-Prot : 71 Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome: JP/HHT syndrome phenotype consists of the coexistence of juvenile polyposis (JIP) and hereditary hemorrhagic telangiectasia (HHT) [MIM:187300] in a single individual. JIP and HHT are autosomal dominant disorders with distinct and non-overlapping clinical features. The former, an inherited gastrointestinal malignancy predisposition, is caused by mutations in SMAD4 or BMPR1A, and the latter is a vascular malformation disorder caused by mutations in ENG or ACVRL1. All four genes encode proteins involved in the transforming-growth-factor-signaling pathway. Although there are reports of patients and families with phenotypes of both disorders combined, the genetic etiology of this association is unknown.

MalaCards based summary : Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia Syndrome, also known as polyposis, generalized juvenile, with pulmonary arteriovenous malformation, is related to hereditary hemorrhagic telangiectasia and alacrima, achalasia, and mental retardation syndrome, and has symptoms including clubbing, anemia and mitral regurgitation. An important gene associated with Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia Syndrome is SMAD4 (SMAD Family Member 4). Affiliated tissues include lung, skin and brain.

OMIM : 53 The JPHT syndrome includes the features of both the juvenile polyposis syndrome (JPS; 174900) and hereditary hemorrhagic telangiectasia (HHT; 187300) in a single individual. JPS is characterized by hamartomatous polyps occurring throughout the gastrointestinal tract, resulting in an increased risk of gastrointestinal cancer, and HHT is a vascular dysplasia characterized by telangiectases of the skin, and oral and nasal mucosa, epistaxis, and arteriovenous malformations (AVMs) of the lungs, liver, brain, and gastrointestinal tract (summary by Gallione et al., 2010). (175050)

Related Diseases for Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia...

Diseases related to Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 hereditary hemorrhagic telangiectasia 10.2
2 alacrima, achalasia, and mental retardation syndrome 10.1
3 leukemia 10.1
4 lymphoblastic leukemia 10.1

Symptoms & Phenotypes for Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia...

Symptoms via clinical synopsis from OMIM:

53
Hematology:
anemia

SkinNailsHairSkin:
telangiectasia

SkeletalHands:
digital clubbing

CardiovascularVascular:
arteriovenous malformations
aortic dilatation (1 family)

AbdomenGastrointestinal:
gastrointestinal hamartomatous polyps
recurrent rectal bleeding

Neoplasia:
increased risk of gastrointestinal cancer

HeadAndNeckNose:
epistaxis

NeurologicCentralNervousSystem:
cerebral arteriovenous malformation

CardiovascularHeart:
mitral valve prolapse (1 family)
mitral valve regurgitation (1 family)
redundant mitral valve leaflets (1 family)

RespiratoryLung:
pulmonary arteriovenous malformation

Skeletal:
hypertrophic osteoarthropathy


Clinical features from OMIM:

175050

Human phenotypes related to Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia Syndrome:

31 (show all 15)
# Description HPO Frequency HPO Source Accession
1 clubbing 31 very rare (1%) HP:0001217
2 anemia 31 HP:0001903
3 mitral regurgitation 31 occasional (7.5%) HP:0001653
4 mitral valve prolapse 31 occasional (7.5%) HP:0001634
5 epistaxis 31 very rare (1%) HP:0000421
6 hematochezia 31 HP:0002573
7 stroke 31 very rare (1%) HP:0001297
8 gastrointestinal carcinoma 31 very rare (1%) HP:0002672
9 hamartomatous polyposis 31 HP:0004390
10 telangiectasia 31 very rare (1%) HP:0001009
11 aortic aneurysm 31 occasional (7.5%) HP:0004942
12 cerebral arteriovenous malformation 31 very rare (1%) HP:0002408
13 pulmonary arteriovenous malformation 31 very rare (1%) HP:0006548
14 hepatic arteriovenous malformation 31 very rare (1%) HP:0006574
15 juvenile gastrointestinal polyposis 31 very rare (1%) HP:0004784

Drugs & Therapeutics for Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia...

Search Clinical Trials , NIH Clinical Center for Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia Syndrome

Genetic Tests for Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia...

Genetic tests related to Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia Syndrome:

# Genetic test Affiliating Genes
1 Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia Syndrome 28 SMAD4

Anatomical Context for Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia...

MalaCards organs/tissues related to Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia Syndrome:

38
Lung, Skin, Brain, Liver

Publications for Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia...

Articles related to Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia Syndrome:

# Title Authors Year
1
Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome in an adolescent with complex chromosomal rearrangement and intellectual disability. ( 25081192 )
2014
2
Recurrent Gastrointestinal Hemorrhage in Treatment with Dasatinib in a Patient Showing SMAD4 Mutation with Acute Lymphoblastic Leukemia Philadelphia Positive and Juvenile Polyposis Hereditary Hemorrhagic Telangiectasia Syndrome. ( 23888243 )
2013

Variations for Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia...

UniProtKB/Swiss-Prot genetic disease variations for Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia Syndrome:

71
# Symbol AA change Variation ID SNP ID
1 SMAD4 p.Gly352Arg VAR_019571 rs121912581
2 SMAD4 p.Gly386Asp VAR_019573 rs121912580

ClinVar genetic disease variations for Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia Syndrome:

6 (show all 25)
# Gene Variation Type Significance SNP ID Assembly Location
1 SMAD4 SMAD4, 1-BP INS insertion Pathogenic
2 SMAD4 NM_005359.5(SMAD4): c.1081C> T (p.Arg361Cys) single nucleotide variant Pathogenic/Likely pathogenic rs80338963 GRCh37 Chromosome 18, 48591918: 48591918
3 SMAD4 NM_005359.5(SMAD4): c.1157G> A (p.Gly386Asp) single nucleotide variant Pathogenic/Likely pathogenic rs121912580 GRCh37 Chromosome 18, 48593406: 48593406
4 SMAD4 SMAD4, 14-BP DEL, NT1612 deletion Pathogenic
5 SMAD4 SMAD4, 2-BP DEL/1-BP INS, 1596CC/T indel Pathogenic
6 SMAD4 NM_005359.5(SMAD4): c.302G> A (p.Trp101Ter) single nucleotide variant Pathogenic rs377767323 GRCh37 Chromosome 18, 48575108: 48575108
7 SMAD4 NM_005359.5(SMAD4): c.692dupG (p.Ser232Glnfs) duplication Pathogenic rs377767334 GRCh37 Chromosome 18, 48584519: 48584519
8 SMAD4 NM_005359.5(SMAD4): c.1054G> A (p.Gly352Arg) single nucleotide variant Pathogenic rs121912581 GRCh37 Chromosome 18, 48591891: 48591891
9 SMAD4 NM_005359.5(SMAD4): c.1055G> A (p.Gly352Glu) single nucleotide variant Pathogenic rs377767345 GRCh37 Chromosome 18, 48591892: 48591892
10 SMAD4 NM_005359.5(SMAD4): c.1082G> T (p.Arg361Leu) single nucleotide variant Pathogenic rs377767347 GRCh37 Chromosome 18, 48591919: 48591919
11 SMAD4 NM_005359.5(SMAD4): c.1088_1090delGTT (p.Cys363del) deletion Pathogenic rs377767349 GRCh37 Chromosome 18, 48591925: 48591927
12 SMAD4 NM_005359.5(SMAD4): c.1102_1103delTC (p.Ser368Glnfs) deletion Pathogenic rs377767351 GRCh37 Chromosome 18, 48591939: 48591940
13 SMAD4 NM_005359.5(SMAD4): c.1148T> A (p.Ile383Lys) single nucleotide variant Pathogenic rs377767355 GRCh37 Chromosome 18, 48593397: 48593397
14 SMAD4 NM_005359.5(SMAD4): c.1333C> T (p.Arg445Ter) single nucleotide variant Pathogenic rs377767360 GRCh37 Chromosome 18, 48603032: 48603032
15 SMAD4 NM_005359.5(SMAD4): c.1586_1587dupTA (p.His530Tyrfs) duplication Pathogenic rs377767376 GRCh37 Chromosome 18, 48604764: 48604765
16 SMAD4 NM_005359.5(SMAD4): c.1594delG (p.Ala532Profs) deletion Pathogenic rs377767378 GRCh37 Chromosome 18, 48604772: 48604772
17 SMAD4 NM_005359.5(SMAD4): c.1596_1597delCCinsT (p.Leu533Serfs) indel Pathogenic rs377767379 GRCh37 Chromosome 18, 48604774: 48604775
18 SMAD4 NM_005359.5(SMAD4): c.1596delC (p.Leu533Serfs) deletion Pathogenic rs377767380 GRCh37 Chromosome 18, 48604774: 48604774
19 SMAD4 NM_005359.5(SMAD4): c.1598T> G (p.Leu533Arg) single nucleotide variant Pathogenic rs377767382 GRCh37 Chromosome 18, 48604776: 48604776
20 SMAD4 NM_005359.5(SMAD4): c.1600C> T (p.Gln534Ter) single nucleotide variant Pathogenic rs377767383 GRCh37 Chromosome 18, 48604778: 48604778
21 SMAD4 NM_005359.5(SMAD4): c.1598T> C (p.Leu533Pro) single nucleotide variant Pathogenic rs377767382 GRCh37 Chromosome 18, 48604776: 48604776
22 SMAD4 NM_005359.5(SMAD4): c.1612_1625delGAAGTACTTCATAC (p.Glu538Hisfs) deletion Pathogenic rs377767385 GRCh37 Chromosome 18, 48604790: 48604803
23 SMAD4 LRG_318t1: c.1228-1229delCA deletion Pathogenic GRCh37 Chromosome 18, 48592248: 48592248
24 SMAD4 NM_005359.5(SMAD4): c.1447+1G> A single nucleotide variant Pathogenic rs377767387 GRCh37 Chromosome 18, 48603147: 48603147
25 SMAD4 NM_005359.5(SMAD4): c.1245_1248delCAGA (p.Asp415Glufs) deletion Pathogenic rs80338965 GRCh37 Chromosome 18, 48593494: 48593497

Expression for Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia...

Search GEO for disease gene expression data for Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia Syndrome.

Pathways for Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia...

GO Terms for Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia...

Sources for Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia...

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