JPHT
MCID: JVN012
MIFTS: 32

Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia Syndrome (JPHT)

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 56 73 29 13 6 71
Polyposis, Generalized Juvenile, with Pulmonary Arteriovenous Malformation 56
Telangiectasia, Hereditary Hemorrhagic, with Juvenile Polyposis Coli 56
Polyposis, Juvenile/hereditary Hemorrhagic Telangiectasia Syndrome 39
Juvenile Polyposis-Hereditary Hemorrhagic Telangiectasia Syndrome 12
Juvenile Polyposis with Hereditary Hemorrhagic Telangiectasia 56
Jp/hht Syndrome 56
Jps/hht 56
Jp-Hht 12
Jp/hht 73
Jpht 56

Characteristics:

OMIM:

56
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 : 73 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 brain, liver and lung, and related phenotypes are mitral valve prolapse and mitral regurgitation

Disease Ontology : 12 A syndrome characterized by hamartomatous polyps in the gastrointestinal tract, telangiectases of the skin, and oral and nasal mucosa, epistaxis, and arteriovenous malformations of the lungs, liver, brain, and gastrointestinal tract that has material basis in heterozygous mutation in SMAD4 on chromosome 18q21.2.

OMIM : 56 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:

(show all 11)
# Related Disease Score Top Affiliating Genes
1 hereditary hemorrhagic telangiectasia 12.0
2 telangiectasis 10.4
3 juvenile polyposis syndrome 10.3
4 arteriovenous malformation 10.3
5 juvenile rheumatoid arthritis 10.3
6 systemic onset juvenile idiopathic arthritis 10.3
7 leukemia, acute lymphoblastic 10.2
8 alacrima, achalasia, and mental retardation syndrome 10.2
9 lymphocytic leukemia 10.2
10 thrombocytopenia 10.2
11 complex chromosomal rearrangement 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:

31 (show all 16)
# Description HPO Frequency HPO Source Accession
1 mitral valve prolapse 31 occasional (7.5%) HP:0001634
2 mitral regurgitation 31 occasional (7.5%) HP:0001653
3 aortic aneurysm 31 occasional (7.5%) HP:0004942
4 aortic dissection 31 very rare (1%) HP:0002647
5 epistaxis 31 very rare (1%) HP:0000421
6 stroke 31 very rare (1%) HP:0001297
7 gastrointestinal carcinoma 31 very rare (1%) HP:0002672
8 juvenile gastrointestinal polyposis 31 very rare (1%) HP:0004784
9 pulmonary arteriovenous malformation 31 very rare (1%) HP:0006548
10 hepatic arteriovenous malformation 31 very rare (1%) HP:0006574
11 cerebral arteriovenous malformation 31 very rare (1%) HP:0002408
12 telangiectasia 31 very rare (1%) HP:0001009
13 clubbing 31 very rare (1%) HP:0001217
14 anemia 31 HP:0001903
15 hematochezia 31 HP:0002573
16 hamartomatous polyposis 31 HP:0004390

Symptoms via clinical synopsis from OMIM:

56
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 29 SMAD4

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

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

40
Brain, Liver, Lung, Skin, Colon, Prostate, Endothelial

Publications for Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia...

Articles related to Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia Syndrome:

(show all 28)
# Title Authors PMID Year
1
SMAD4 mutation segregating in a family with juvenile polyposis, aortopathy, and mitral valve dysfunction. 56 6
21465659 2011
2
SMAD4 mutations found in unselected HHT patients. 56 6
16613914 2006
3
A combined syndrome of juvenile polyposis and hereditary haemorrhagic telangiectasia associated with mutations in MADH4 (SMAD4). 56 6
15031030 2004
4
Novel de novo mutation of MADH4/SMAD4 in a patient with juvenile polyposis. 56 6
12116240 2002
5
Generalized juvenile polyposis with pulmonary arteriovenous malformations and hypertrophic osteoarthropathy. 56 6
6604412 1983
6
Prevalence of thoracic aortopathy in patients with juvenile Polyposis Syndrome-Hereditary Hemorrhagic Telangiectasia due to SMAD4. 56
25931195 2015
7
International guidelines for the diagnosis and management of hereditary haemorrhagic telangiectasia. 6
19553198 2011
8
Overlapping spectra of SMAD4 mutations in juvenile polyposis (JP) and JP-HHT syndrome. 56
20101697 2010
9
Hypermanganesemia, hereditary hemorrhagic telangiectasia, brain abscess: the hepatic connection. 56
18824676 2008
10
Gastric juvenile polyposis associated with germline SMAD4 mutation. 6
15754356 2005
11
Hereditary Hemorrhagic Telangiectasia 6
20301525 2000
12
Diagnostic criteria for hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber syndrome). 6
10751092 2000
13
Mutations in DPC4 (SMAD4) cause juvenile polyposis syndrome, but only account for a minority of cases. 6
9811934 1998
14
Mutations in the SMAD4/DPC4 gene in juvenile polyposis. 6
9582123 1998
15
Comparative mutational analysis of DPC4 (Smad4) in prostatic and colorectal carcinomas. 6
9285566 1997
16
Somatic alterations of the DPC4 gene in human colorectal cancers in vivo. 6
8898652 1996
17
Colonic hamartomatous polyposis associated with hypertrophic osteoarthropathy. 56
8078721 1994
18
Association of juvenile and adenomatous polyposis with pulmonary arteriovenous malformation and hypertrophic osteoarthropathy. 56
2388124 1990
19
Association of hypertrophic osteoarthropathy with gastrointestinal polyposis. 56
3872584 1985
20
Hereditary generalized juvenile polyposis associated with pulmonary arteriovenous malformation. 56
7372073 1980
21
Clinical and genetic challenges in a family with history of childhood polyp, aortopathy, and clinical diagnosis of hereditary hemorrhagic teleangiectasia (HHT). 61
27212857 2016
22
Processed Pseudogene Confounding Deletion/Duplication Assays for SMAD4. 61
26165824 2015
23
Increase of circulating endothelial cells in patients with Hereditary Hemorrhagic Telangiectasia. 61
25465912 2015
24
Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome in an adolescent with complex chromosomal rearrangement and intellectual disability. 61
25081192 2014
25
Appreciating the broad clinical features of SMAD4 mutation carriers: a multicenter chart review. 61
24525918 2014
26
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. 61
23888243 2013
27
SMAD4 haploinsufficiency associates with augmented colonic inflammation in select humans and mice. 61
23090737 2012
28
Hereditary haemorrhagic telangiectasia: current views on genetics and mechanisms of disease. 61
15879500 2006

Variations for Juvenile Polyposis/hereditary Hemorrhagic Telangiectasia...

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

6 (show all 36) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 SMAD4 SMAD4, 14-BP DEL, NT1612deletion Pathogenic 8547
2 SMAD4 SMAD4, 2-BP DEL/1-BP INS, 1596CC/Tindel Pathogenic 8548
3 SMAD4 NM_005359.5(SMAD4):c.302G>A (p.Trp101Ter)SNV Pathogenic 24798 rs377767323 18:48575108-48575108 18:51048738-51048738
4 SMAD4 NM_005359.5(SMAD4):c.692dupG (p.Ser232Glnfs)duplication Pathogenic 24811 rs377767334 18:48584513-48584514 18:51058143-51058144
5 SMAD4 NM_005359.5(SMAD4):c.1054G>A (p.Gly352Arg)SNV Pathogenic 24827 rs121912581 18:48591891-48591891 18:51065521-51065521
6 SMAD4 NM_005359.5(SMAD4):c.1055G>A (p.Gly352Glu)SNV Pathogenic 24828 rs377767345 18:48591892-48591892 18:51065522-51065522
7 SMAD4 NM_005359.5(SMAD4):c.1082G>A (p.Arg361His)SNV Pathogenic 24832 rs377767347 18:48591919-48591919 18:51065549-51065549
8 SMAD4 NM_005359.5(SMAD4):c.1082G>T (p.Arg361Leu)SNV Pathogenic 24833 rs377767347 18:48591919-48591919 18:51065549-51065549
9 SMAD4 NM_005359.5(SMAD4):c.1088_1090delGTT (p.Cys363del)deletion Pathogenic 24835 rs377767349 18:48591923-48591925 18:51065553-51065555
10 SMAD4 NM_005359.5(SMAD4):c.1102_1103delTC (p.Ser368Glnfs)short repeat Pathogenic 24837 rs377767351 18:48591936-48591937 18:51065566-51065567
11 SMAD4 NM_005359.5(SMAD4):c.1148T>A (p.Ile383Lys)SNV Pathogenic 24840 rs377767355 18:48593397-48593397 18:51067027-51067027
12 SMAD4 NM_005359.5(SMAD4):c.1333C>T (p.Arg445Ter)SNV Pathogenic 24850 rs377767360 18:48603032-48603032 18:51076662-51076662
13 SMAD4 NM_005359.5(SMAD4):c.1586_1587dup (p.His530Tyrfs)duplication Pathogenic 24869 rs1555687599 18:48604763-48604764 18:51078393-51078394
14 SMAD4 NM_005359.5(SMAD4):c.1594delG (p.Ala532Profs)deletion Pathogenic 24870 rs377767378 18:48604770-48604770 18:51078400-51078400
15 SMAD4 NM_005359.5(SMAD4):c.1596_1597delCCinsT (p.Leu533Serfs)indel Pathogenic 24871 rs377767379 18:48604774-48604775 18:51078404-51078405
16 SMAD4 NM_005359.5(SMAD4):c.1596delC (p.Leu533Serfs)deletion Pathogenic 24872 rs377767380 18:48604773-48604773 18:51078403-51078403
17 SMAD4 NM_005359.5(SMAD4):c.1598T>G (p.Leu533Arg)SNV Pathogenic 24874 rs377767382 18:48604776-48604776 18:51078406-51078406
18 SMAD4 NM_005359.5(SMAD4):c.1600C>T (p.Gln534Ter)SNV Pathogenic 24875 rs377767383 18:48604778-48604778 18:51078408-51078408
19 SMAD4 NM_005359.5(SMAD4):c.1598T>C (p.Leu533Pro)SNV Pathogenic 24876 rs377767382 18:48604776-48604776 18:51078406-51078406
20 SMAD4 NM_005359.5(SMAD4):c.1612_1625del (p.Glu538Hisfs)deletion Pathogenic 24878 rs377767385 18:48604788-48604801 18:51078418-51078431
21 SMAD4 NM_005359.5:c.1228-1229delCAdeletion Pathogenic 24879 rs483352871 18:48592247-48592247 18:51065877-51065877
22 SMAD4 NM_005359.5(SMAD4):c.1498A>G (p.Ile500Val)SNV Pathogenic 30150 rs281875322 18:48604676-48604676 18:51078306-51078306
23 SMAD4 NM_005359.5(SMAD4):c.1447+1G>ASNV Pathogenic 38740 rs377767387 18:48603147-48603147 18:51076777-51076777
24 SMAD4 SMAD4, 1-BP INSinsertion Pathogenic 8542
25 SMAD4 NM_005359.5(SMAD4):c.1081C>T (p.Arg361Cys)SNV Pathogenic 8543 rs80338963 18:48591918-48591918 18:51065548-51065548
26 SMAD4 NM_005359.5(SMAD4):c.1245_1248delCAGA (p.Asp415Glufs)deletion Pathogenic 142253 rs80338965 18:48593491-48593494 18:51067121-51067124
27 SMAD4 NM_005359.5(SMAD4):c.1308+2T>CSNV Pathogenic 548563 rs1555686624 18:48593559-48593559 18:51067189-51067189
28 SMAD4 NM_005359.5(SMAD4):c.1157G>A (p.Gly386Asp)SNV Pathogenic/Likely pathogenic 8545 rs121912580 18:48593406-48593406 18:51067036-51067036
29 SMAD4 NM_005359.5(SMAD4):c.677C>T (p.Ala226Val)SNV Conflicting interpretations of pathogenicity 182869 rs539739051 18:48584504-48584504 18:51058134-51058134
30 SMAD4 NM_005359.5(SMAD4):c.20C>T (p.Thr7Met)SNV Uncertain significance 183733 rs372316981 18:48573436-48573436 18:51047066-51047066
31 SMAD4 NM_005359.5(SMAD4):c.535A>G (p.Ile179Val)SNV Uncertain significance 185866 rs542392980 18:48581231-48581231 18:51054861-51054861
32 SMAD4 NM_005359.5(SMAD4):c.463A>G (p.Ser155Gly)SNV Uncertain significance 374977 rs1057519259 18:48581159-48581159 18:51054789-51054789
33 SMAD4 NM_005359.5(SMAD4):c.181A>G (p.Ile61Val)SNV Uncertain significance 419954 rs1064794204 18:48573597-48573597 18:51047227-51047227
34 SMAD4 NM_005359.5(SMAD4):c.566G>A (p.Arg189His)SNV Uncertain significance 460557 rs759288477 18:48581262-48581262 18:51054892-51054892
35 SMAD4 NM_005359.5(SMAD4):c.1219G>C (p.Val407Leu)SNV Uncertain significance 460530 rs147621330 18:48593468-48593468 18:51067098-51067098
36 SMAD4 NM_005359.5(SMAD4):c.1106A>G (p.Asn369Ser)SNV Uncertain significance 142165 rs139569694 18:48591943-48591943 18:51065573-51065573

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

73
# Symbol AA change Variation ID SNP ID
1 SMAD4 p.Gly352Arg VAR_019571 rs121912581
2 SMAD4 p.Gly386Asp VAR_019573 rs121912580

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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