PGGSS
MCID: PRG017
MIFTS: 49

Paraganglioma and Gastric Stromal Sarcoma (PGGSS)

Categories: Cancer diseases, Endocrine diseases, Gastrointestinal diseases, Genetic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Paraganglioma and Gastric Stromal Sarcoma

MalaCards integrated aliases for Paraganglioma and Gastric Stromal Sarcoma:

Name: Paraganglioma and Gastric Stromal Sarcoma 57 53 59 75 29 13 6 73
Carney-Stratakis Syndrome 57 53 59 75
Paraganglioma and Gastrointestinal Stromal Tumor 57 53 75
Carney Dyad 53 59
Carney-Stratakis Dyad of Paraganglioma and Gastric Stromal Sarcoma 53
Paraganglioma, Gastric Stromal Sarcoma 40
Gastrointestinal Stromal Tumors 73
Gist-Paraganglioma Dyad 59
Paraganglioma and Gist 53
Carney-Stratakis Dyad 59
Pggss 75

Characteristics:

Orphanet epidemiological data:

59
carney-stratakis syndrome
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Adolescent,Adult;

Classifications:

Orphanet: 59  
Rare endocrine diseases


Summaries for Paraganglioma and Gastric Stromal Sarcoma

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 97286Disease definitionCarney-Stratakis syndrome is a recently described familial syndrome characterized by gastrointestinal stromal tumors (GIST) and paragangliomas, often at multiple sites.EpidemiologyIt is a very rare syndrome reported in less than 20 unrelated families to date. It presents at a young age (median age: 19 years) with an apparently equal ratio of male and female patients.Clinical descriptionPatients with Carney-Stratakis syndrome have both GIST and paraganglioma. The gastric stromal sarcomas are multifocal and the paragangliomas are multicentric. The clinical spectrum of Carney-Stratakis syndrome varies widely, depending on the localization and the size of the tumors, and may include a palpable mass, dysphagia, abdominal pain, weight loss, hematemesis, melena, obstruction, perforation, cranial nerve palsies, tinnitus and hearing loss. GIST are intramural mesenchymal tumors of the gastrointestinal tract that originate from stem cells with characteristics of the interstitial cells of Cajal (the pacemaker cells which regulate peristalsis in the digestive tract). Paragangliomas are usually benign tumors that occur without clinical evidence of oversecretion and that arise within the sympathetic nervous system from cells of the paraganglia.EtiologyThe vast majority of Carney-Stratakis syndrome cases are due to germline mutations of the succinate dehydrogenase (SDH) subunit genesSDHB, SDHC and SDHD.Diagnostic methodsDiagnosis is made by clinical and radiologic examination, and confirmed immunohistochemically. Genetic testing to determine if SDH defects may be contributing to tumor growth or recurrence should be offered to pediatric GIST patients.Differential diagnosisThe main differential diagnosis includes Carney triad.Genetic counselingPredisposition to developing these tumors is inherited in an autosomal dominant manner with incomplete penetrance.Management and treatmentTreatment modalities are surgery, embolization and radiotherapy. Chemotherapy with imatinib mesylate may be helpful for some patients with advanced-stage GIST. Targeting SDH function may potentiallybe useful in treating Carney-Stratakis syndrome patients but, at present, there are no drugs that restore SDH function. Life-long follow-up should be offered to patients with Carney-Stratakis syndrome.Visit the Orphanet disease page for more resources.

MalaCards based summary : Paraganglioma and Gastric Stromal Sarcoma, also known as carney-stratakis syndrome, is related to gastrointestinal stromal tumor and pheochromocytoma. An important gene associated with Paraganglioma and Gastric Stromal Sarcoma is SDHD (Succinate Dehydrogenase Complex Subunit D), and among its related pathways/superpathways are Carbon metabolism and Pyruvate metabolism and Citric Acid (TCA) cycle. The drugs Gleevec and Sutent have been mentioned in the context of this disorder. Affiliated tissues include testes, liver and bone, and related phenotypes are dysphagia and hearing impairment

UniProtKB/Swiss-Prot : 75 Paraganglioma and gastric stromal sarcoma: Gastrointestinal stromal tumors may be sporadic or inherited in an autosomal dominant manner, alone or as a component of a syndrome associated with other tumors, such as in the context of neurofibromatosis type 1 (NF1). Patients have both gastrointestinal stromal tumors and paragangliomas. Susceptibility to the tumors was inherited in an apparently autosomal dominant manner, with incomplete penetrance.

Description from OMIM: 606864

Related Diseases for Paraganglioma and Gastric Stromal Sarcoma

Graphical network of the top 20 diseases related to Paraganglioma and Gastric Stromal Sarcoma:



Diseases related to Paraganglioma and Gastric Stromal Sarcoma

Symptoms & Phenotypes for Paraganglioma and Gastric Stromal Sarcoma

Clinical features from OMIM:

606864

Human phenotypes related to Paraganglioma and Gastric Stromal Sarcoma:

59 32 (show all 11)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 dysphagia 59 32 frequent (33%) Frequent (79-30%) HP:0002015
2 hearing impairment 59 32 frequent (33%) Frequent (79-30%) HP:0000365
3 cranial nerve paralysis 59 32 frequent (33%) Frequent (79-30%) HP:0006824
4 abdominal pain 59 32 frequent (33%) Frequent (79-30%) HP:0002027
5 weight loss 59 32 frequent (33%) Frequent (79-30%) HP:0001824
6 intestinal obstruction 59 32 frequent (33%) Frequent (79-30%) HP:0005214
7 gastrointestinal hemorrhage 59 32 frequent (33%) Frequent (79-30%) HP:0002239
8 tinnitus 59 32 frequent (33%) Frequent (79-30%) HP:0000360
9 gastrointestinal stroma tumor 59 32 hallmark (90%) Very frequent (99-80%) HP:0100723
10 paraganglioma 59 32 hallmark (90%) Very frequent (99-80%) HP:0002668
11 neoplasm of the gastrointestinal tract 32 HP:0007378

GenomeRNAi Phenotypes related to Paraganglioma and Gastric Stromal Sarcoma according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased shRNA abundance (Z-score > 2) GR00366-A-132 9.17 SDHC
2 Increased shRNA abundance (Z-score > 2) GR00366-A-188 9.17 SDHC SDHD
3 Increased shRNA abundance (Z-score > 2) GR00366-A-197 9.17 SDHC
4 Increased shRNA abundance (Z-score > 2) GR00366-A-63 9.17 SDHC
5 Increased shRNA abundance (Z-score > 2) GR00366-A-81 9.17 SDHC SDHD

Drugs & Therapeutics for Paraganglioma and Gastric Stromal Sarcoma

FDA approved drugs:

# Drug Name Active Ingredient(s) 18 Company Approval Date
1
Gleevec 18 49 IMATINIB MESYLATE Novartis May 2001
2
Sutent 18 49 SUNITINIB MALATE Pfizer May 2011/ January 2006
3
Votrient 18 49 PAZOPANIB HYDROCHLORIDE GlaxoSmithKline April 2012/ October of 2009

Search Clinical Trials , NIH Clinical Center for Paraganglioma and Gastric Stromal Sarcoma

Inferred drug relations via UMLS 73 / NDF-RT 51 :


Genetic Tests for Paraganglioma and Gastric Stromal Sarcoma

Genetic tests related to Paraganglioma and Gastric Stromal Sarcoma:

# Genetic test Affiliating Genes
1 Paraganglioma and Gastric Stromal Sarcoma 29 SDHB SDHC SDHD

Anatomical Context for Paraganglioma and Gastric Stromal Sarcoma

MalaCards organs/tissues related to Paraganglioma and Gastric Stromal Sarcoma:

41
Testes, Liver, Bone, Lung, Kidney, Pancreas, Lymph Node

Publications for Paraganglioma and Gastric Stromal Sarcoma

Articles related to Paraganglioma and Gastric Stromal Sarcoma:

# Title Authors Year
1
Simultaneous KIT mutation and succinate dehydrogenase (SDH) deficiency in a patient with a gastrointestinal stromal tumour and Carney-Stratakis syndrome: a case report. ( 25130709 )
2014
2
Carney Stratakis syndrome in a patient with SDHD mutation. ( 22638655 )
2012
3
Carney triad versus Carney Stratakis syndrome: two cases which illustrate the difficulty in distinguishing between these conditions in individual patients. ( 20119652 )
2010
4
Clinical and molecular genetics of patients with the Carney-Stratakis syndrome and germline mutations of the genes coding for the succinate dehydrogenase subunits SDHB, SDHC, and SDHD. ( 17667967 )
2008
5
Familial paraganglioma and gastric stromal sarcoma: a new syndrome distinct from the Carney triad. ( 11857563 )
2002

Variations for Paraganglioma and Gastric Stromal Sarcoma

ClinVar genetic disease variations for Paraganglioma and Gastric Stromal Sarcoma:

6 (show top 50) (show all 324)
# Gene Variation Type Significance SNP ID Assembly Location
1 SDHD NM_003002.3(SDHD): c.112C> T (p.Arg38Ter) single nucleotide variant Pathogenic rs80338843 GRCh37 Chromosome 11, 111958640: 111958640
2 SDHD NM_003002.3(SDHD): c.112C> T (p.Arg38Ter) single nucleotide variant Pathogenic rs80338843 GRCh38 Chromosome 11, 112087916: 112087916
3 SDHD NM_003002.3(SDHD): c.34G> A (p.Gly12Ser) single nucleotide variant Conflicting interpretations of pathogenicity rs34677591 GRCh37 Chromosome 11, 111957665: 111957665
4 SDHD NM_003002.3(SDHD): c.34G> A (p.Gly12Ser) single nucleotide variant Conflicting interpretations of pathogenicity rs34677591 GRCh38 Chromosome 11, 112086941: 112086941
5 SDHD NM_003002.3(SDHD): c.242C> T (p.Pro81Leu) single nucleotide variant Pathogenic rs80338844 GRCh37 Chromosome 11, 111959663: 111959663
6 SDHD NM_003002.3(SDHD): c.242C> T (p.Pro81Leu) single nucleotide variant Pathogenic rs80338844 GRCh38 Chromosome 11, 112088939: 112088939
7 SDHD NM_003002.3(SDHD): c.305A> T (p.His102Leu) single nucleotide variant Likely pathogenic rs104894302 GRCh37 Chromosome 11, 111959726: 111959726
8 SDHD NM_003002.3(SDHD): c.305A> T (p.His102Leu) single nucleotide variant Likely pathogenic rs104894302 GRCh38 Chromosome 11, 112089002: 112089002
9 SDHD NM_003002.3(SDHD): c.341A> G (p.Tyr114Cys) single nucleotide variant Pathogenic rs104894304 GRCh37 Chromosome 11, 111965555: 111965555
10 SDHD NM_003002.3(SDHD): c.341A> G (p.Tyr114Cys) single nucleotide variant Pathogenic rs104894304 GRCh38 Chromosome 11, 112094831: 112094831
11 SDHD NM_003002.3(SDHD): c.64C> T (p.Arg22Ter) single nucleotide variant Pathogenic rs104894306 GRCh37 Chromosome 11, 111958592: 111958592
12 SDHD NM_003002.3(SDHD): c.64C> T (p.Arg22Ter) single nucleotide variant Pathogenic rs104894306 GRCh38 Chromosome 11, 112087868: 112087868
13 SDHD NM_003002.3(SDHD): c.191_192delTC (p.Leu64Profs) deletion Pathogenic rs387906358 GRCh37 Chromosome 11, 111959612: 111959613
14 SDHD NM_003002.3(SDHD): c.191_192delTC (p.Leu64Profs) deletion Pathogenic rs387906358 GRCh38 Chromosome 11, 112088888: 112088889
15 SDHD NM_003002.3(SDHD): c.149A> G (p.His50Arg) single nucleotide variant Conflicting interpretations of pathogenicity rs11214077 GRCh37 Chromosome 11, 111958677: 111958677
16 SDHD NM_003002.3(SDHD): c.149A> G (p.His50Arg) single nucleotide variant Conflicting interpretations of pathogenicity rs11214077 GRCh38 Chromosome 11, 112087953: 112087953
17 SDHD NM_003002.3(SDHD): c.129G> A (p.Trp43Ter) single nucleotide variant Pathogenic rs104894308 GRCh37 Chromosome 11, 111958657: 111958657
18 SDHD NM_003002.3(SDHD): c.129G> A (p.Trp43Ter) single nucleotide variant Pathogenic rs104894308 GRCh38 Chromosome 11, 112087933: 112087933
19 SDHD NM_003002.3(SDHD): c.57delG (p.Leu20Cysfs) deletion Pathogenic rs587776649 GRCh38 Chromosome 11, 112087861: 112087861
20 SDHD NM_003002.3(SDHD): c.57delG (p.Leu20Cysfs) deletion Pathogenic rs587776649 GRCh37 Chromosome 11, 111958585: 111958585
21 SDHD NM_003002.3(SDHD): c.433C> A (p.His145Asn) single nucleotide variant Uncertain significance rs121908984 GRCh37 Chromosome 11, 111965647: 111965647
22 SDHD NM_003002.3(SDHD): c.433C> A (p.His145Asn) single nucleotide variant Uncertain significance rs121908984 GRCh38 Chromosome 11, 112094923: 112094923
23 SDHC NM_003001.3(SDHC): c.405+1G> A single nucleotide variant Pathogenic/Likely pathogenic rs587776653 GRCh37 Chromosome 1, 161326631: 161326631
24 SDHC NM_003001.3(SDHC): c.405+1G> A single nucleotide variant Pathogenic/Likely pathogenic rs587776653 GRCh38 Chromosome 1, 161356841: 161356841
25 SDHB NM_003000.2(SDHB): c.423+1G> C single nucleotide variant Pathogenic rs398122805 GRCh37 Chromosome 1, 17355094: 17355094
26 SDHB NM_003000.2(SDHB): c.423+1G> C single nucleotide variant Pathogenic rs398122805 GRCh38 Chromosome 1, 17028599: 17028599
27 SDHB NM_003000.2(SDHB): c.8C> G (p.Ala3Gly) single nucleotide variant Conflicting interpretations of pathogenicity rs11203289 GRCh37 Chromosome 1, 17380507: 17380507
28 SDHB NM_003000.2(SDHB): c.8C> G (p.Ala3Gly) single nucleotide variant Conflicting interpretations of pathogenicity rs11203289 GRCh38 Chromosome 1, 17054012: 17054012
29 SDHD NM_003002.3(SDHD): c.400T> G (p.Leu134Val) single nucleotide variant Uncertain significance rs200851392 GRCh37 Chromosome 11, 111965614: 111965614
30 SDHD NM_003002.3(SDHD): c.400T> G (p.Leu134Val) single nucleotide variant Uncertain significance rs200851392 GRCh38 Chromosome 11, 112094890: 112094890
31 SDHB NM_003000.2(SDHB): c.18C> A (p.Ala6=) single nucleotide variant Benign rs2746462 GRCh37 Chromosome 1, 17380497: 17380497
32 SDHB NM_003000.2(SDHB): c.18C> A (p.Ala6=) single nucleotide variant Benign rs2746462 GRCh38 Chromosome 1, 17054002: 17054002
33 SDHB NM_003000.2(SDHB): c.424-16_424-14dupTTC duplication Conflicting interpretations of pathogenicity rs386134266 GRCh37 Chromosome 1, 17354374: 17354376
34 SDHB NM_003000.2(SDHB): c.424-16_424-14dupTTC duplication Conflicting interpretations of pathogenicity rs386134266 GRCh38 Chromosome 1, 17027879: 17027881
35 SDHD NM_003002.3(SDHD): c.204C> T (p.Ser68=) single nucleotide variant Benign rs9919552 GRCh37 Chromosome 11, 111959625: 111959625
36 SDHD NM_003002.3(SDHD): c.204C> T (p.Ser68=) single nucleotide variant Benign rs9919552 GRCh38 Chromosome 11, 112088901: 112088901
37 SDHB NM_003000.2(SDHB): c.170A> G (p.His57Arg) single nucleotide variant Benign/Likely benign rs35962811 GRCh38 Chromosome 1, 17044791: 17044791
38 SDHB NM_003000.2(SDHB): c.170A> G (p.His57Arg) single nucleotide variant Benign/Likely benign rs35962811 GRCh37 Chromosome 1, 17371286: 17371286
39 SDHD NM_003002.3(SDHD): c.101T> G (p.Phe34Cys) single nucleotide variant Conflicting interpretations of pathogenicity rs141802836 GRCh38 Chromosome 11, 112087905: 112087905
40 SDHD NM_003002.3(SDHD): c.101T> G (p.Phe34Cys) single nucleotide variant Conflicting interpretations of pathogenicity rs141802836 GRCh37 Chromosome 11, 111958629: 111958629
41 SDHD NM_003002.3(SDHD): c.278A> G (p.Tyr93Cys) single nucleotide variant Uncertain significance rs142135772 GRCh38 Chromosome 11, 112088975: 112088975
42 SDHD NM_003002.3(SDHD): c.278A> G (p.Tyr93Cys) single nucleotide variant Uncertain significance rs142135772 GRCh37 Chromosome 11, 111959699: 111959699
43 SDHD NM_003002.3(SDHD): c.255G> T (p.Leu85Phe) single nucleotide variant Uncertain significance rs199517389 GRCh38 Chromosome 11, 112088952: 112088952
44 SDHD NM_003002.3(SDHD): c.255G> T (p.Leu85Phe) single nucleotide variant Uncertain significance rs199517389 GRCh37 Chromosome 11, 111959676: 111959676
45 SDHD NM_003002.3(SDHD): c.155C> A (p.Ser52Ter) single nucleotide variant Pathogenic rs587782210 GRCh37 Chromosome 11, 111958683: 111958683
46 SDHD NM_003002.3(SDHD): c.155C> A (p.Ser52Ter) single nucleotide variant Pathogenic rs587782210 GRCh38 Chromosome 11, 112087959: 112087959
47 SDHB NM_003000.2(SDHB): c.72+1G> T single nucleotide variant Pathogenic rs587782703 GRCh37 Chromosome 1, 17380442: 17380442
48 SDHB NM_003000.2(SDHB): c.72+1G> T single nucleotide variant Pathogenic rs587782703 GRCh38 Chromosome 1, 17053947: 17053947
49 SDHD NM_003002.3(SDHD): c.205G> A (p.Glu69Lys) single nucleotide variant Conflicting interpretations of pathogenicity rs202198133 GRCh38 Chromosome 11, 112088902: 112088902
50 SDHD NM_003002.3(SDHD): c.205G> A (p.Glu69Lys) single nucleotide variant Conflicting interpretations of pathogenicity rs202198133 GRCh37 Chromosome 11, 111959626: 111959626

Expression for Paraganglioma and Gastric Stromal Sarcoma

Search GEO for disease gene expression data for Paraganglioma and Gastric Stromal Sarcoma.

Pathways for Paraganglioma and Gastric Stromal Sarcoma

GO Terms for Paraganglioma and Gastric Stromal Sarcoma

Cellular components related to Paraganglioma and Gastric Stromal Sarcoma according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrion GO:0005739 9.56 SDHB SDHC SDHD TIMM8B
2 mitochondrial inner membrane GO:0005743 9.46 SDHB SDHC SDHD TIMM8B
3 respiratory chain complex II GO:0045273 8.96 SDHB SDHC
4 mitochondrial respiratory chain complex II, succinate dehydrogenase complex (ubiquinone) GO:0005749 8.8 SDHB SDHC SDHD

Biological processes related to Paraganglioma and Gastric Stromal Sarcoma according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 oxidation-reduction process GO:0055114 9.5 SDHB SDHC SDHD
2 electron transport chain GO:0022900 9.26 SDHB SDHC
3 aerobic respiration GO:0009060 9.16 SDHB SDHC
4 mitochondrial electron transport, succinate to ubiquinone GO:0006121 8.96 SDHC SDHD
5 tricarboxylic acid cycle GO:0006099 8.8 SDHB SDHC SDHD

Molecular functions related to Paraganglioma and Gastric Stromal Sarcoma according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 metal ion binding GO:0046872 9.62 SDHB SDHC SDHD TIMM8B
2 electron transfer activity GO:0009055 9.33 SDHB SDHC SDHD
3 heme binding GO:0020037 9.26 SDHC SDHD
4 ubiquinone binding GO:0048039 9.13 SDHB SDHC SDHD
5 succinate dehydrogenase (ubiquinone) activity GO:0008177 8.8 SDHB SDHC SDHD

Sources for Paraganglioma and Gastric Stromal Sarcoma

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 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 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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