JPHT
MCID: JVN012
MIFTS: 29

Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia Syndrome (JPHT)

Categories: Cardiovascular diseases, Gastrointestinal diseases, 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 58 76 30 13 6 74
Polyposis, Generalized Juvenile, with Pulmonary Arteriovenous Malformation 58
Telangiectasia, Hereditary Hemorrhagic, with Juvenile Polyposis Coli 58
Polyposis, Juvenile/hereditary Hemorrhagic Telangiectasia Syndrome 41
Juvenile Polyposis with Hereditary Hemorrhagic Telangiectasia 58
Jp/hht Syndrome 58
Jps/hht 58
Jp/hht 76
Jpht 58

Characteristics:

OMIM:

58
Inheritance:
autosomal dominant

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


HPO:

33
juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome:
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia...

UniProtKB/Swiss-Prot : 76 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 telangiectasis. An important gene associated with Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia Syndrome is SMAD4 (SMAD Family Member 4). Affiliated tissues include lung, skin and brain, and related phenotypes are mitral valve prolapse and mitral regurgitation

OMIM : 58 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 10.4
2 telangiectasis 10.4
3 juvenile polyposis syndrome 10.3
4 arthritis 10.3
5 juvenile rheumatoid arthritis 10.3
6 leukemia, acute lymphoblastic 10.2
7 alacrima, achalasia, and mental retardation syndrome 10.2
8 leukemia 10.2
9 lymphocytic leukemia 10.2

Graphical network of the top 20 diseases related to Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia Syndrome:



Diseases related to Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia Syndrome

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

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

33 (show all 16)
# Description HPO Frequency HPO Source Accession
1 mitral valve prolapse 33 occasional (7.5%) HP:0001634
2 mitral regurgitation 33 occasional (7.5%) HP:0001653
3 aortic aneurysm 33 occasional (7.5%) HP:0004942
4 aortic dissection 33 very rare (1%) HP:0002647
5 epistaxis 33 very rare (1%) HP:0000421
6 stroke 33 very rare (1%) HP:0001297
7 gastrointestinal carcinoma 33 very rare (1%) HP:0002672
8 juvenile gastrointestinal polyposis 33 very rare (1%) HP:0004784
9 pulmonary arteriovenous malformation 33 very rare (1%) HP:0006548
10 hepatic arteriovenous malformation 33 very rare (1%) HP:0006574
11 cerebral arteriovenous malformation 33 very rare (1%) HP:0002408
12 telangiectasia 33 very rare (1%) HP:0001009
13 clubbing 33 very rare (1%) HP:0001217
14 anemia 33 HP:0001903
15 hematochezia 33 HP:0002573
16 hamartomatous polyposis 33 HP:0004390

Symptoms via clinical synopsis from OMIM:

58
Hematology:
anemia

Respiratory Lung:
pulmonary arteriovenous malformation

Skin Nails Hair Skin:
telangiectasia

Cardiovascular Heart:
mitral valve prolapse (1 family)
mitral valve regurgitation (1 family)
redundant mitral valve leaflets (1 family)

Abdomen Gastrointestinal:
gastrointestinal hamartomatous polyps
recurrent rectal bleeding

Neoplasia:
increased risk of gastrointestinal cancer

Head And Neck Nose:
epistaxis

Neurologic Central Nervous System:
cerebral arteriovenous malformation

Skeletal Hands:
digital clubbing

Cardiovascular Vascular:
arteriovenous malformations
aortic dilatation (in some patients)
aortic dissection (rare)

Skeletal:
hypertrophic osteoarthropathy

Clinical features from OMIM:

175050

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 30 SMAD4

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

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

42
Lung, Skin, Brain, Liver, Prostate

Publications for Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia...

Articles related to Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia Syndrome:

(show all 14)
# 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
3
International guidelines for the diagnosis and management of hereditary haemorrhagic telangiectasia. ( 19553198 )
2011
4
SMAD4 mutation segregating in a family with juvenile polyposis, aortopathy, and mitral valve dysfunction. ( 21465659 )
2011
5
SMAD4 mutations found in unselected HHT patients. ( 16613914 )
2006
6
Gastric juvenile polyposis associated with germline SMAD4 mutation. ( 15754356 )
2005
7
A combined syndrome of juvenile polyposis and hereditary haemorrhagic telangiectasia associated with mutations in MADH4 (SMAD4). ( 15031030 )
2004
8
Novel de novo mutation of MADH4/SMAD4 in a patient with juvenile polyposis. ( 12116240 )
2002
9
Diagnostic criteria for hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber syndrome). ( 10751092 )
2000
10
Mutations in DPC4 (SMAD4) cause juvenile polyposis syndrome, but only account for a minority of cases. ( 9811934 )
1998
11
Mutations in the SMAD4/DPC4 gene in juvenile polyposis. ( 9582123 )
1998
12
Comparative mutational analysis of DPC4 (Smad4) in prostatic and colorectal carcinomas. ( 9285566 )
1997
13
Somatic alterations of the DPC4 gene in human colorectal cancers in vivo. ( 8898652 )
1996
14
Generalized juvenile polyposis with pulmonary arteriovenous malformations and hypertrophic osteoarthropathy. ( 6604412 )
1983

Variations for Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia...

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

76
# 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 top 50) (show all 70)
# 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 rs80338963 GRCh37 Chromosome 18, 48591918: 48591918
3 SMAD4 NM_005359.5(SMAD4): c.1081C> T (p.Arg361Cys) single nucleotide variant Pathogenic rs80338963 GRCh38 Chromosome 18, 51065548: 51065548
4 SMAD4 NM_005359.5(SMAD4): c.1157G> A (p.Gly386Asp) single nucleotide variant Pathogenic/Likely pathogenic rs121912580 GRCh37 Chromosome 18, 48593406: 48593406
5 SMAD4 NM_005359.5(SMAD4): c.1157G> A (p.Gly386Asp) single nucleotide variant Pathogenic/Likely pathogenic rs121912580 GRCh38 Chromosome 18, 51067036: 51067036
6 SMAD4 SMAD4, 14-BP DEL, NT1612 deletion Pathogenic
7 SMAD4 SMAD4, 2-BP DEL/1-BP INS, 1596CC/T indel Pathogenic
8 SMAD4 NM_005359.5(SMAD4): c.302G> A (p.Trp101Ter) single nucleotide variant Pathogenic rs377767323 GRCh37 Chromosome 18, 48575108: 48575108
9 SMAD4 NM_005359.5(SMAD4): c.302G> A (p.Trp101Ter) single nucleotide variant Pathogenic rs377767323 GRCh38 Chromosome 18, 51048738: 51048738
10 SMAD4 NM_005359.5(SMAD4): c.692dupG (p.Ser232Glnfs) duplication Pathogenic rs377767334 GRCh37 Chromosome 18, 48584519: 48584519
11 SMAD4 NM_005359.5(SMAD4): c.692dupG (p.Ser232Glnfs) duplication Pathogenic rs377767334 GRCh38 Chromosome 18, 51058149: 51058149
12 SMAD4 NM_005359.5(SMAD4): c.1054G> A (p.Gly352Arg) single nucleotide variant Pathogenic rs121912581 GRCh37 Chromosome 18, 48591891: 48591891
13 SMAD4 NM_005359.5(SMAD4): c.1054G> A (p.Gly352Arg) single nucleotide variant Pathogenic rs121912581 GRCh38 Chromosome 18, 51065521: 51065521
14 SMAD4 NM_005359.5(SMAD4): c.1055G> A (p.Gly352Glu) single nucleotide variant Pathogenic rs377767345 GRCh37 Chromosome 18, 48591892: 48591892
15 SMAD4 NM_005359.5(SMAD4): c.1055G> A (p.Gly352Glu) single nucleotide variant Pathogenic rs377767345 GRCh38 Chromosome 18, 51065522: 51065522
16 SMAD4 NM_005359.5(SMAD4): c.1082G> A (p.Arg361His) single nucleotide variant Pathogenic rs377767347 GRCh37 Chromosome 18, 48591919: 48591919
17 SMAD4 NM_005359.5(SMAD4): c.1082G> A (p.Arg361His) single nucleotide variant Pathogenic rs377767347 GRCh38 Chromosome 18, 51065549: 51065549
18 SMAD4 NM_005359.5(SMAD4): c.1082G> T (p.Arg361Leu) single nucleotide variant Pathogenic rs377767347 GRCh37 Chromosome 18, 48591919: 48591919
19 SMAD4 NM_005359.5(SMAD4): c.1082G> T (p.Arg361Leu) single nucleotide variant Pathogenic rs377767347 GRCh38 Chromosome 18, 51065549: 51065549
20 SMAD4 NM_005359.5(SMAD4): c.1088_1090delGTT (p.Cys363del) deletion Pathogenic rs377767349 GRCh37 Chromosome 18, 48591925: 48591927
21 SMAD4 NM_005359.5(SMAD4): c.1088_1090delGTT (p.Cys363del) deletion Pathogenic rs377767349 GRCh38 Chromosome 18, 51065555: 51065557
22 SMAD4 NM_005359.5(SMAD4): c.1102_1103delTC (p.Ser368Glnfs) deletion Pathogenic rs377767351 GRCh37 Chromosome 18, 48591939: 48591940
23 SMAD4 NM_005359.5(SMAD4): c.1102_1103delTC (p.Ser368Glnfs) deletion Pathogenic rs377767351 GRCh38 Chromosome 18, 51065569: 51065570
24 SMAD4 NM_005359.5(SMAD4): c.1148T> A (p.Ile383Lys) single nucleotide variant Pathogenic rs377767355 GRCh37 Chromosome 18, 48593397: 48593397
25 SMAD4 NM_005359.5(SMAD4): c.1148T> A (p.Ile383Lys) single nucleotide variant Pathogenic rs377767355 GRCh38 Chromosome 18, 51067027: 51067027
26 SMAD4 NM_005359.5(SMAD4): c.1333C> T (p.Arg445Ter) single nucleotide variant Pathogenic rs377767360 GRCh37 Chromosome 18, 48603032: 48603032
27 SMAD4 NM_005359.5(SMAD4): c.1333C> T (p.Arg445Ter) single nucleotide variant Pathogenic rs377767360 GRCh38 Chromosome 18, 51076662: 51076662
28 SMAD4 NM_005359.5(SMAD4): c.1586_1587dupTA (p.His530Tyrfs) duplication Pathogenic rs1555687599 GRCh37 Chromosome 18, 48604764: 48604765
29 SMAD4 NM_005359.5(SMAD4): c.1586_1587dupTA (p.His530Tyrfs) duplication Pathogenic rs1555687599 GRCh38 Chromosome 18, 51078394: 51078395
30 SMAD4 NM_005359.5(SMAD4): c.1594delG (p.Ala532Profs) deletion Pathogenic rs377767378 GRCh37 Chromosome 18, 48604772: 48604772
31 SMAD4 NM_005359.5(SMAD4): c.1594delG (p.Ala532Profs) deletion Pathogenic rs377767378 GRCh38 Chromosome 18, 51078402: 51078402
32 SMAD4 NM_005359.5(SMAD4): c.1596_1597delCCinsT (p.Leu533Serfs) indel Pathogenic rs377767379 GRCh37 Chromosome 18, 48604774: 48604775
33 SMAD4 NM_005359.5(SMAD4): c.1596_1597delCCinsT (p.Leu533Serfs) indel Pathogenic rs377767379 GRCh38 Chromosome 18, 51078404: 51078405
34 SMAD4 NM_005359.5(SMAD4): c.1596delC (p.Leu533Serfs) deletion Pathogenic rs377767380 GRCh37 Chromosome 18, 48604774: 48604774
35 SMAD4 NM_005359.5(SMAD4): c.1596delC (p.Leu533Serfs) deletion Pathogenic rs377767380 GRCh38 Chromosome 18, 51078404: 51078404
36 SMAD4 NM_005359.5(SMAD4): c.1598T> G (p.Leu533Arg) single nucleotide variant Pathogenic rs377767382 GRCh37 Chromosome 18, 48604776: 48604776
37 SMAD4 NM_005359.5(SMAD4): c.1598T> G (p.Leu533Arg) single nucleotide variant Pathogenic rs377767382 GRCh38 Chromosome 18, 51078406: 51078406
38 SMAD4 NM_005359.5(SMAD4): c.1600C> T (p.Gln534Ter) single nucleotide variant Pathogenic rs377767383 GRCh37 Chromosome 18, 48604778: 48604778
39 SMAD4 NM_005359.5(SMAD4): c.1600C> T (p.Gln534Ter) single nucleotide variant Pathogenic rs377767383 GRCh38 Chromosome 18, 51078408: 51078408
40 SMAD4 NM_005359.5(SMAD4): c.1598T> C (p.Leu533Pro) single nucleotide variant Pathogenic rs377767382 GRCh37 Chromosome 18, 48604776: 48604776
41 SMAD4 NM_005359.5(SMAD4): c.1598T> C (p.Leu533Pro) single nucleotide variant Pathogenic rs377767382 GRCh38 Chromosome 18, 51078406: 51078406
42 SMAD4 NM_005359.5(SMAD4): c.1612_1625del (p.Glu538Hisfs) deletion Pathogenic rs377767385 GRCh37 Chromosome 18, 48604790: 48604803
43 SMAD4 NM_005359.5(SMAD4): c.1612_1625del (p.Glu538Hisfs) deletion Pathogenic rs377767385 GRCh38 Chromosome 18, 51078420: 51078433
44 SMAD4 LRG_318t1: c.1228-1229del deletion Pathogenic rs483352871 GRCh37 Chromosome 18, 48592248: 48592248
45 SMAD4 NM_005359.5(SMAD4): c.1498A> G (p.Ile500Val) single nucleotide variant Pathogenic rs281875322 GRCh37 Chromosome 18, 48604676: 48604676
46 SMAD4 NM_005359.5(SMAD4): c.1498A> G (p.Ile500Val) single nucleotide variant Pathogenic rs281875322 GRCh38 Chromosome 18, 51078306: 51078306
47 SMAD4 NM_005359.5(SMAD4): c.1447+1G> A single nucleotide variant Pathogenic rs377767387 GRCh37 Chromosome 18, 48603147: 48603147
48 SMAD4 NM_005359.5(SMAD4): c.1447+1G> A single nucleotide variant Pathogenic rs377767387 GRCh38 Chromosome 18, 51076777: 51076777
49 SMAD4 NM_005359.5(SMAD4): c.1106A> G (p.Asn369Ser) single nucleotide variant Uncertain significance rs139569694 GRCh37 Chromosome 18, 48591943: 48591943
50 SMAD4 NM_005359.5(SMAD4): c.1106A> G (p.Asn369Ser) single nucleotide variant Uncertain significance rs139569694 GRCh38 Chromosome 18, 51065573: 51065573

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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