CD
MCID: CWD010
MIFTS: 66

Cowden Syndrome (CD)

Categories: Cancer diseases, Cardiovascular diseases, Eye diseases, Fetal diseases, Gastrointestinal diseases, Genetic diseases, Neuronal diseases, Rare diseases, Reproductive diseases, Skin diseases

Aliases & Classifications for Cowden Syndrome

MalaCards integrated aliases for Cowden Syndrome:

Name: Cowden Syndrome 12 75 53 25 59 37 29 6 15 40
Multiple Hamartoma Syndrome 12 53 25 59
Cowden Disease 12 53 25 59
Lhermitte-Duclos Disease 12 75 53
Cowden's Disease 75 53 25
Mham 53 25
Cs 53 25
Cd 53 25
Dysplastic Gangliocytoma of the Cerebellum 53
Dysplastic Gangliocytoma of Cerebellum 12
Cowden's Syndrome 25

Characteristics:

Orphanet epidemiological data:

59
cowden syndrome
Inheritance: Autosomal dominant; Prevalence: 1-9/1000000 (Netherlands),1-9/1000000 (Europe); Age of onset: All ages; Age of death: any age;

Classifications:



External Ids:

Disease Ontology 12 DOID:6457
KEGG 37 H01222
MeSH 44 D006223
NCIt 50 C3076
SNOMED-CT 68 58037000
MESH via Orphanet 45 D006223
ICD10 via Orphanet 34 Q85.8
UMLS via Orphanet 73 C0018553
Orphanet 59 ORPHA201
UMLS 72 C0018553 C0391826

Summaries for Cowden Syndrome

Genetics Home Reference : 25 Cowden syndrome is a disorder characterized by multiple noncancerous, tumor-like growths called hamartomas and an increased risk of developing certain cancers. Almost everyone with Cowden syndrome develops hamartomas. These growths are most commonly found on the skin and mucous membranes (such as the lining of the mouth and nose), but they can also occur in the intestine and other parts of the body. The growth of hamartomas on the skin and mucous membranes typically becomes apparent by a person's late twenties. Cowden syndrome is associated with an increased risk of developing several types of cancer, particularly cancers of the breast, a gland in the lower neck called the thyroid, and the lining of the uterus (the endometrium). Other cancers that have been identified in people with Cowden syndrome include colorectal cancer, kidney cancer, and a form of skin cancer called melanoma. Compared with the general population, people with Cowden syndrome develop these cancers at younger ages, often beginning in their thirties or forties. Other diseases of the breast, thyroid, and endometrium are also common in Cowden syndrome. Additional signs and symptoms can include an enlarged head (macrocephaly) and a rare, noncancerous brain tumor called Lhermitte-Duclos disease. A small percentage of affected individuals have delayed development or intellectual disability. The features of Cowden syndrome overlap with those of another disorder called Bannayan-Riley-Ruvalcaba syndrome. People with Bannayan-Riley-Ruvalcaba syndrome also develop hamartomas and other noncancerous tumors. Both conditions can be caused by mutations in the PTEN gene. Some people with Cowden syndrome have had relatives diagnosed with Bannayan-Riley-Ruvalcaba syndrome, and other individuals have had the characteristic features of both conditions. Based on these similarities, researchers have proposed that Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome represent a spectrum of overlapping features known as PTEN hamartoma tumor syndrome instead of two distinct conditions. PTEN PTEN Some people have some of the characteristic features of Cowden syndrome, particularly the cancers associated with this condition, but do not meet the strict criteria for a diagnosis of Cowden syndrome. These individuals are often described as having Cowden-like syndrome.

MalaCards based summary : Cowden Syndrome, also known as multiple hamartoma syndrome, is related to cowden syndrome 1 and proteus syndrome, and has symptoms including seizures and action tremor. An important gene associated with Cowden Syndrome is PTEN (Phosphatase And Tensin Homolog), and among its related pathways/superpathways are Focal Adhesion and Endometrial cancer. The drugs Lactitol and Fluorodeoxyglucose F18 have been mentioned in the context of this disorder. Affiliated tissues include breast, thyroid and cerebellum, and related phenotypes are generalized hyperkeratosis and palmoplantar keratoderma

Disease Ontology : 12 An autosomal dominant disease characterized by multiple noncancerous, tumor-like growths (hamartomas) and an increased risk of certain forms of cancer, especially breast, thyroid and endometrium.

NIH Rare Diseases : 53 Cowden syndrome is an inherited condition that is characterized primarily by multiple, noncancerous growths (called hamartomas) on various parts of the body. People with the syndrome usually have large head (macrocephaly), benign tumors of the hair follicle (trichilemmomas), and white papules with a smooth surface in the mouth (papillomatous papules), starting by the late 20s. It is considered part of the PTEN Hamartoma Tumor Syndrome spectrum which also includes Bannayan-Riley-Ruvalcaba syndrome and Proteus syndrome. People who have Cowden syndrome are at an increased risk of developing certain types of cancer, such as breast, thyroid, and endometrial (lining of the uterus) cancer. Most cases are caused by mutations in the PTEN gene and are inherited in an autosomal dominant manner. Management typically includes screening for associated tumors and/or prophylactic surgeries.

KEGG : 37
Cowden syndrome (CS) is a autosomal dominant inherited cancer syndrome characterized by benign and malignant breast, thyroid, and endometrial neoplasias in addition to cutaneous findings and macrocephaly. Germ line PTEN mutations have been found in 85% of those with CS. A large heterogeneous group of individuals with Cowden-like syndrome, who have various combinations of Cowden syndrome features but who do not meet Cowden syndrome diagnostic criteria, have PTEN mutations less than 10% of the time. In the absence of germline PTEN mutations, approximately 10% of individuals with Cowden syndrome or Cowden-like syndrome harbor germline succinate dehydrogenase variants SDHB and SDHD.

Wikipedia : 75 Cowden syndrome (also known as Cowden's disease and multiple hamartoma syndrome) is an autosomal... more...

Related Diseases for Cowden Syndrome

Diseases in the Cowden Syndrome family:

Cowden Syndrome 1 Cowden Syndrome 4
Cowden Syndrome 5 Cowden Syndrome 6
Cowden Syndrome 7

Diseases related to Cowden Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 1049)
# Related Disease Score Top Affiliating Genes
1 cowden syndrome 1 34.3 TNS1 PTEN KLLN EGFR CDKN3 BMPR1A
2 proteus syndrome 33.3 PTEN PIK3CA CDKN3 AKT1
3 gastric cancer 31.8 SMAD4 PTEN PIK3CA MIR21 EGFR AKT1
4 endometrial cancer 31.1 PTEN PIK3CA EGFR CDKN3 BRCA2 AKT1
5 lipomatosis 31.1 SDHB PTEN PIK3CA
6 juvenile polyposis syndrome 31.1 SMAD4 PTEN BMPR1A
7 neurofibromatosis, type iv, of riccardi 30.9 SDHD SDHC SDHB
8 ovarian cancer 1 30.9 PIK3CA BRCA2 AKT1
9 peutz-jeghers syndrome 30.8 SMAD4 PTEN BRCA2
10 endometrial adenocarcinoma 30.8 PTEN EGFR AKT1
11 adenocarcinoma 30.8 SMAD4 PTEN PIK3CA EGFR AKT1
12 squamous cell carcinoma 30.6 SMAD4 PTEN PIK3CA EGFR AKT1
13 ductal carcinoma in situ 30.5 EGFR BRCA2 AKT1
14 suppression of tumorigenicity 12 30.5 SMAD4 PTEN PIK3CA AKT1
15 hereditary paraganglioma-pheochromocytoma syndromes 30.5 TIMM8B SDHD SDHC SDHB
16 glioblastoma multiforme 30.5 PTEN PIK3CA MIR21 EGFR AKT1
17 uterine carcinosarcoma 30.5 PTEN PIK3CA EGFR
18 breast adenocarcinoma 30.5 SMAD4 PTEN PIK3CA EGFR AKT1
19 von hippel-lindau syndrome 30.4 SDHD SDHC SDHB
20 li-fraumeni syndrome 30.4 PTEN EGFR BRCA2
21 brain cancer 30.4 PTEN PIK3CA EGFR BRCA2 AKT1
22 gastric adenocarcinoma 30.4 SMAD4 PTEN PIK3CA EGFR AKT1
23 macrocephaly/autism syndrome 30.3 PTEN KLLN
24 small cell cancer of the lung 30.2 PTEN PIK3CA MIR21 EGFR AKT1
25 glioblastoma 30.2 PTEN PIK3CA MIR21 EGFR BRCA2 AKT1
26 pheochromocytoma 30.2 TIMM8B SDHD SDHC SDHB
27 gastrointestinal stromal tumor 30.1 SDHD SDHC SDHB PTEN EGFR AKT1
28 pancreatic neuroendocrine tumor 30.0 PIK3CA BRCA2
29 cervical cancer 30.0 SMAD4 PTEN PIK3CA MIR21 AKT1
30 ovarian cancer 29.9 PTEN PIK3CA MIR21 EGFR BRCA2 AKT1
31 esophageal cancer 29.8 SMAD4 PTEN PIK3CA MIR21 EGFR AKT1
32 glioma 29.8 PTEN PIK3CA MIR21 MIR19A EGFR BRCA2
33 pancreatic cancer 29.7 SMAD4 PIK3CA MIR21 EGFR BRCA2 AKT1
34 medulloblastoma 29.7 PTEN PIK3CA MIR19A EGFR BRCA2 AKT1
35 breast cancer 29.6 SMAD4 PTEN PIK3CA MIR21 KLLN EGFR
36 hepatocellular carcinoma 29.3 SMAD4 PTEN PIK3CA MIR21 MIR19A EGFR
37 prostate cancer 28.9 PTEN PIK3CA MIR21 EGFR CDKN3 BRCA2
38 cowden syndrome 4 12.7
39 cowden syndrome 7 12.7
40 cowden syndrome 5 12.6
41 cowden syndrome 6 12.6
42 cockayne syndrome 12.1
43 xeroderma pigmentosum, complementation group d 11.9
44 xeroderma pigmentosum, complementation group g 11.9
45 chanarin-dorfman syndrome 11.9
46 castleman disease 11.9
47 cervical dystonia 11.8
48 crouzon syndrome 11.8
49 xeroderma pigmentosum, complementation group f 11.8
50 xeroderma pigmentosum, complementation group b 11.8

Graphical network of the top 20 diseases related to Cowden Syndrome:



Diseases related to Cowden Syndrome

Symptoms & Phenotypes for Cowden Syndrome

Human phenotypes related to Cowden Syndrome:

59 32 (show top 50) (show all 57)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 generalized hyperkeratosis 59 32 hallmark (90%) Very frequent (99-80%) HP:0005595
2 palmoplantar keratoderma 59 32 hallmark (90%) Very frequent (99-80%) HP:0000982
3 macule 59 32 hallmark (90%) Very frequent (99-80%) HP:0012733
4 papule 59 32 hallmark (90%) Very frequent (99-80%) HP:0200034
5 goiter 59 32 hallmark (90%) Very frequent (99-80%) HP:0000853
6 breast carcinoma 59 32 hallmark (90%) Very frequent (99-80%) HP:0003002
7 colorectal polyposis 59 32 hallmark (90%) Very frequent (99-80%) HP:0200063
8 papilloma 59 32 hallmark (90%) Very frequent (99-80%) HP:0012740
9 conjunctival hamartoma 59 32 hallmark (90%) Very frequent (99-80%) HP:0100780
10 macrocephaly 59 32 frequent (33%) Frequent (79-30%) HP:0000256
11 intellectual disability 59 32 frequent (33%) Frequent (79-30%) HP:0001249
12 ataxia 59 32 frequent (33%) Frequent (79-30%) HP:0001251
13 macroglossia 59 32 frequent (33%) Frequent (79-30%) HP:0000158
14 global developmental delay 59 32 frequent (33%) Frequent (79-30%) HP:0001263
15 cognitive impairment 59 32 frequent (33%) Frequent (79-30%) HP:0100543
16 subcutaneous nodule 59 32 frequent (33%) Frequent (79-30%) HP:0001482
17 cavernous hemangioma 59 32 frequent (33%) Frequent (79-30%) HP:0001048
18 mucosal telangiectasiae 59 32 frequent (33%) Frequent (79-30%) HP:0100579
19 melanocytic nevus 59 32 frequent (33%) Frequent (79-30%) HP:0000995
20 meningioma 59 32 frequent (33%) Frequent (79-30%) HP:0002858
21 abnormality of the penis 59 32 frequent (33%) Frequent (79-30%) HP:0000036
22 furrowed tongue 59 32 frequent (33%) Frequent (79-30%) HP:0000221
23 hamartomatous polyposis 59 32 frequent (33%) Frequent (79-30%) HP:0004390
24 adenoma sebaceum 59 32 frequent (33%) Frequent (79-30%) HP:0009720
25 lipoma 59 32 frequent (33%) Frequent (79-30%) HP:0012032
26 pectus excavatum 59 32 occasional (7.5%) Occasional (29-5%) HP:0000767
27 high palate 59 32 occasional (7.5%) Occasional (29-5%) HP:0000218
28 seizures 59 32 occasional (7.5%) Occasional (29-5%) HP:0001250
29 failure to thrive 59 32 occasional (7.5%) Occasional (29-5%) HP:0001508
30 scoliosis 59 32 occasional (7.5%) Occasional (29-5%) HP:0002650
31 kyphosis 59 32 occasional (7.5%) Occasional (29-5%) HP:0002808
32 hearing impairment 59 32 occasional (7.5%) Occasional (29-5%) HP:0000365
33 cataract 59 32 occasional (7.5%) Occasional (29-5%) HP:0000518
34 increased intracranial pressure 59 32 occasional (7.5%) Occasional (29-5%) HP:0002516
35 short stature 59 32 occasional (7.5%) Occasional (29-5%) HP:0004322
36 hypopigmented skin patches 59 32 occasional (7.5%) Occasional (29-5%) HP:0001053
37 autism 59 32 occasional (7.5%) Occasional (29-5%) HP:0000717
38 myopia 59 32 occasional (7.5%) Occasional (29-5%) HP:0000545
39 melanoma 59 32 occasional (7.5%) Occasional (29-5%) HP:0002861
40 renal cell carcinoma 59 32 occasional (7.5%) Occasional (29-5%) HP:0005584
41 brachydactyly 59 32 occasional (7.5%) Occasional (29-5%) HP:0001156
42 cellular immunodeficiency 59 32 occasional (7.5%) Occasional (29-5%) HP:0005374
43 multiple cafe-au-lait spots 59 32 occasional (7.5%) Occasional (29-5%) HP:0007565
44 gynecomastia 59 32 occasional (7.5%) Occasional (29-5%) HP:0000771
45 enlarged polycystic ovaries 59 32 occasional (7.5%) Occasional (29-5%) HP:0008675
46 abnormal cerebellum morphology 59 32 occasional (7.5%) Occasional (29-5%) HP:0001317
47 follicular thyroid carcinoma 59 32 occasional (7.5%) Occasional (29-5%) HP:0006731
48 bone cyst 59 32 occasional (7.5%) Occasional (29-5%) HP:0012062
49 endometrial carcinoma 59 32 occasional (7.5%) Occasional (29-5%) HP:0012114
50 neoplasm 59 Frequent (79-30%)

UMLS symptoms related to Cowden Syndrome:


seizures, action tremor

GenomeRNAi Phenotypes related to Cowden Syndrome according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability GR00055-A-2 10.34 EGFR PIK3CA
2 Decreased viability GR00221-A-1 10.34 AKT1 BMPR1A EGFR PIK3CA SDHD
3 Decreased viability GR00221-A-2 10.34 AKT1 BMPR1A PIK3CA SDHD
4 Decreased viability GR00221-A-3 10.34 AKT1 BMPR1A
5 Decreased viability GR00221-A-4 10.34 AKT1 BMPR1A EGFR PIK3CA SDHD
6 Decreased viability GR00381-A-1 10.34 SDHD
7 Decreased viability GR00402-S-2 10.34 AKT1 BMPR1A EGFR PIK3CA SDHD
8 Decreased sensitivity to paclitaxel GR00112-A-0 9.16 PTEN SMAD4
9 Increased mitotic index GR00110-A-0 8.92 BMPR1A SDHD SMAD4 TNS1

MGI Mouse Phenotypes related to Cowden Syndrome:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 homeostasis/metabolism MP:0005376 10.15 AKT1 BMPR1A BRCA2 EGFR PIK3CA PTEN
2 endocrine/exocrine gland MP:0005379 10.13 AKT1 BMPR1A BRCA2 EGFR PIK3CA PTEN
3 embryo MP:0005380 10.11 AKT1 BMPR1A BRCA2 EGFR PIK3CA PTEN
4 hematopoietic system MP:0005397 10.1 AKT1 BMPR1A BRCA2 EGFR PTEN SDHB
5 mortality/aging MP:0010768 10.07 AKT1 BMPR1A BRCA2 EGFR PIK3CA PTEN
6 integument MP:0010771 9.97 AKT1 BMPR1A BRCA2 EGFR PIK3CA PTEN
7 neoplasm MP:0002006 9.85 AKT1 BMPR1A BRCA2 EGFR PIK3CA PTEN
8 normal MP:0002873 9.65 AKT1 BMPR1A BRCA2 EGFR PTEN SDHB
9 reproductive system MP:0005389 9.32 AKT1 BMPR1A BRCA2 EGFR PIK3CA PTEN

Drugs & Therapeutics for Cowden Syndrome

Drugs for Cowden Syndrome (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Lactitol Investigational Phase 2 585-86-4, 585-88-6 493591
2 Fluorodeoxyglucose F18 Phase 2
3 Radiopharmaceuticals Phase 2

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 A Pilot Study of Sirolimus (Rapamycin, Rapamune[Registered Trademark]) in Subjects With Cowden Syndrome or Other Syndromes Characterized by Germline Mutations in PTEN Completed NCT00971789 Phase 2 sirolimus
2 A Phase I/II, Multi-center, Open-label Study of BGT226, Administered Orally in Adult Patients With Advanced Solid Malignancies Including Patients With Advanced Breast Cancer Completed NCT00600275 Phase 1, Phase 2 BGT226
3 Phase 2 Study of Everolimus Therapy in Patients With Birt-Hogg-Dube Syndrome (BHD)-Associated Kidney Cancer or Sporadic Chromophobe Renal Cancer Terminated NCT02504892 Phase 2 Everolimus
4 Open Label Phase II Study of Everolimus (RAD001) in Patients With Segmental Overgrowth Syndrome Withdrawn NCT02569125 Phase 2 Everolimus
5 Clinical, Genetic, Behavioral, Laboratory and Epidemiologic Characterization of Individuals and Families at High Risk of Breast/Ovarian Cancer Completed NCT00040222
6 French Digestive Polyposis Cohorte Recruiting NCT01987518

Search NIH Clinical Center for Cowden Syndrome

Genetic Tests for Cowden Syndrome

Genetic tests related to Cowden Syndrome:

# Genetic test Affiliating Genes
1 Cowden Syndrome 29

Anatomical Context for Cowden Syndrome

MalaCards organs/tissues related to Cowden Syndrome:

41
Breast, Thyroid, Cerebellum, Uterus, Skin, Kidney, Brain

Publications for Cowden Syndrome

Articles related to Cowden Syndrome:

(show top 50) (show all 657)
# Title Authors PMID Year
1
Germline Heterozygous Variants in SEC23B Are Associated with Cowden Syndrome and Enriched in Apparently Sporadic Thyroid Cancer. 38 71
26522472 2015
2
Genetic/familial high-risk assessment: breast and ovarian, version 1.2014. 38 71
25190698 2014
3
Germline PIK3CA and AKT1 mutations in Cowden and Cowden-like syndromes. 38 71
23246288 2013
4
Succinate dehydrogenase gene variants and their role in Cowden syndrome. 38 71
21565294 2011
5
Germline epigenetic regulation of KILLIN in Cowden and Cowden-like syndrome. 38 71
21177507 2010
6
Germline mutations and variants in the succinate dehydrogenase genes in Cowden and Cowden-like syndromes. 38 71
18678321 2008
7
Clinical genetics evaluation in identifying the etiology of autism spectrum disorders: 2013 guideline revisions. 71
23519317 2013
8
The first Dutch SDHB founder deletion in paraganglioma-pheochromocytoma patients. 71
19368708 2009
9
Differential expression of PTEN-targeting microRNAs miR-19a and miR-21 in Cowden syndrome. 38 88
18460397 2008
10
Absence of somatic SDHD mutations in sporadic neuroendocrine tumors and detection of two germline variants in paraganglioma patients. 71
12386824 2002
11
Identification of novel SDHD mutations in patients with phaeochromocytoma and/or paraganglioma. 71
12111639 2002
12
Alterations of the SDHD gene locus in midgut carcinoids, Merkel cell carcinomas, pheochromocytomas, and abdominal paragangliomas. 71
12007193 2002
13
Germline SDHD mutation in paraganglioma of the spinal cord. 71
11526495 2001
14
Somatic and occult germ-line mutations in SDHD, a mitochondrial complex II gene, in nonfamilial pheochromocytoma. 71
11156372 2000
15
Mutations in SDHD, a mitochondrial complex II gene, in hereditary paraganglioma. 71
10657297 2000
16
Hereditary Gastrointestinal Cancer Syndromes: Role of Imaging in Screening, Diagnosis, and Management. 38
31373866 2019
17
Intramucosal fat is uncommon in large bowel polyps but raises three differential diagnoses. 38
31097491 2019
18
Clinical, Imaging, and Pathologic Features of Conditions with Combined Esophageal and Cutaneous Manifestations. 38
31419189 2019
19
The Clinical Spectrum of PTEN Mutations. 38
31433956 2019
20
Left atrial cavernous haemangioma presenting with cardiac tamponade in a patient with Cowden syndrome. 38
31289165 2019
21
Enlarging left atrial haemangioma in a patient with Cowden syndrome. 38
31352392 2019
22
Bilateral Recurrent Dysplastic Cerebellar Gangliocytoma (Lhermitte-Duclos Disease) in Cowden Syndrome: A Case Report and Literature Review. 38
30905649 2019
23
Spectrum of gastrointestinal tract pathology in a multicenter cohort of 43 Cowden syndrome patients. 38
31273317 2019
24
A Pilot Study of Sirolimus in Subjects with Cowden Syndrome or Other Syndromes Characterized by Germline Mutations in PTEN. 38
31350329 2019
25
Letter to the Editor Regarding "Giant Cerebral Aneurysm in a Patient with Cowden Syndrome Treated with Surgical Clipping". 38
31266126 2019
26
In Reply to the Letter to Editor Regarding "Giant Cerebral Aneurysm in a Patient with Cowden Syndrome Treated with Surgical Clipping". 38
31266127 2019
27
Cowden syndrome caused by a novel mutation: Endoscopy aided diagnosis. 38
30952542 2019
28
Is Malignant Germ-Cell Tumor Associated With Cowden Syndrome? 38
30733184 2019
29
Current Knowledge of Germline Genetic Risk Factors for the Development of Non-Medullary Thyroid Cancer. 38
31247975 2019
30
PTEN Hamartoma Tumor Syndrome: A Clinical Overview. 38
31216739 2019
31
Genetic and developmental disorders of the oral mucosa: Epidemiology; molecular mechanisms; diagnostic criteria; management. 38
31090139 2019
32
Novel PTEN mutation in Cowden syndrome: case report with late diagnosis and non-malignant course. 38
31220904 2019
33
Cowden syndrome: gastrointestinal manifestations of an infrequent polyposis. 38
31096272 2019
34
Exome sequencing in 51 early onset non-familial CRC cases. 38
30809968 2019
35
Giant cerebral aneurysm in a patient with Cowden syndrome treated with surgical clipping; a case report. 38
30904793 2019
36
Non-HPV Papillary Lesions of the Oral Mucosa: Clinical and Histopathologic Features of Reactive and Neoplastic Conditions. 38
30693457 2019
37
Undifferentiated pleomorphic sarcoma in a patient with Cowden syndrome after radiotherapy for breast cancer. 38
30047560 2019
38
A case of Cowden syndrome associated with melanoma: the role of the dermatologist. 38
30717572 2019
39
Ovarian Clear Cell Carcinoma in Cowden Syndrome. 38
30659124 2019
40
Endometrial Endometrioid Carcinoma With Ovarian Metastasis Showing Morula-like Features in a Patient With Cowden Syndrome: A Case Report. 38
30676432 2019
41
Follicular thyroid carcinoma metastatic to skin: a small papule and a big diagnostic change. 38
30726467 2019
42
A novel missense PTEN mutation identified in a patient with macrocephaly and developmental delay. 38
31149344 2019
43
PTEN Mutation Identified in Patient Diagnosed with Simultaneous Multiple Cancers. 38
29510612 2019
44
Constipation with megacolon in a 36-year-old man: a rare presentation of MEN2B from Sri Lanka. 38
30642858 2019
45
Variable expressivity and novel PTEN mutations in Cowden syndrome. 38
30316882 2019
46
Challenges in Managing Patients with Hereditary Cancer at Gynecological Services. 38
31263500 2019
47
Familial Syndromes Involving Meningiomas Provide Mechanistic Insight Into Sporadic Disease. 38
29660026 2018
48
[Dermal Clues to Systemic Diseases]. 38
30440073 2018
49
Cowden Syndrome: A Cause of Pulmonary Cysts. 38
30142139 2018
50
Gastrointestinal: Multiple venous malformations and polyps of the small intestine in Cowden syndrome. 38
29952025 2018

Variations for Cowden Syndrome

ClinVar genetic disease variations for Cowden Syndrome:

6 (show top 50) (show all 164)
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 PIK3CA NM_006218.4(PIK3CA): c.1093G> A (p.Glu365Lys) single nucleotide variant Pathogenic rs1064793732 3:178922324-178922324 3:179204536-179204536
2 PIK3CA NM_006218.4(PIK3CA): c.1133G> A (p.Cys378Tyr) single nucleotide variant Pathogenic rs397514565 3:178922364-178922364 3:179204576-179204576
3 PIK3CA NM_006218.4(PIK3CA): c.3129G> T (p.Met1043Ile) single nucleotide variant Pathogenic rs121913283 3:178952074-178952074 3:179234286-179234286
4 PTEN NM_000314.7(PTEN): c.118G> T (p.Glu40Ter) single nucleotide variant Pathogenic rs869312778 10:89653820-89653820 10:87894063-87894063
5 PTEN NM_000314.7(PTEN): c.424del (p.Arg142fs) deletion Pathogenic rs869312779 10:89692940-89692940 10:87933183-87933183
6 PTEN NM_000314.7(PTEN): c.765_766AG[1] (p.Glu256fs) short repeat Pathogenic rs869312780 10:89717742-89717743 10:87957985-87957986
7 PTEN NM_000314.7(PTEN): c.406T> C (p.Cys136Arg) single nucleotide variant Pathogenic rs786201044 10:89692922-89692922 10:87933165-87933165
8 PIK3CA NM_006218.4(PIK3CA): c.3139C> T (p.His1047Tyr) single nucleotide variant Pathogenic rs121913281 3:178952084-178952084 3:179234296-179234296
9 PTEN NM_000314.7(PTEN): c.697C> T (p.Arg233Ter) single nucleotide variant Pathogenic rs121909219 10:89717672-89717672 10:87957915-87957915
10 SDHB NM_003000.2(SDHB): c.591del (p.Ser198fs) deletion Pathogenic rs1060503757 1:17350519-17350519 1:17024024-17024024
11 PIK3CA NM_006218.4(PIK3CA): c.1030G> A (p.Val344Met) single nucleotide variant Pathogenic/Likely pathogenic rs1057519942 3:178921548-178921548 3:179203760-179203760
12 PIK3CA NM_006218.4(PIK3CA): c.3129G> A (p.Met1043Ile) single nucleotide variant Pathogenic/Likely pathogenic rs121913283 3:178952074-178952074 3:179234286-179234286
13 PTEN NM_000314.7(PTEN): c.486C> G (p.Asp162Glu) single nucleotide variant Likely pathogenic rs869312777 10:89693002-89693002 10:87933245-87933245
14 PTEN NM_000314.7(PTEN): c.344A> G (p.Asp115Gly) single nucleotide variant Likely pathogenic rs869312775 10:89692860-89692860 10:87933103-87933103
15 PTEN NM_000314.7(PTEN): c.408T> G (p.Cys136Trp) single nucleotide variant Likely pathogenic rs869312776 10:89692924-89692924 10:87933167-87933167
16 PTEN NM_000314.7(PTEN): c.1023del (p.Phe341fs) deletion Likely pathogenic 10:89720872-89720872 10:87961115-87961115
17 SDHB NM_003000.2(SDHB): c.487T> C (p.Ser163Pro) single nucleotide variant Conflicting interpretations of pathogenicity rs33927012 1:17354297-17354297 1:17027802-17027802
18 SDHB NM_003000.2(SDHB): c.8C> G (p.Ala3Gly) single nucleotide variant Conflicting interpretations of pathogenicity rs11203289 1:17380507-17380507 1:17054012-17054012
19 SDHB NM_003000.2(SDHB): c.200+7A> G single nucleotide variant Conflicting interpretations of pathogenicity rs371329778 1:17371249-17371249 1:17044754-17044754
20 PIK3CA NM_006218.4(PIK3CA): c.2985C> T (p.Ala995=) single nucleotide variant Conflicting interpretations of pathogenicity rs201884756 3:178951930-178951930 3:179234142-179234142
21 SDHB NM_003000.2(SDHB): c.650G> A (p.Arg217His) single nucleotide variant Conflicting interpretations of pathogenicity rs747518441 1:17349218-17349218 1:17022723-17022723
22 PTEN NM_000314.7(PTEN): c.838A> G (p.Ile280Val) single nucleotide variant Conflicting interpretations of pathogenicity rs1474354667 10:89720687-89720687 10:87960930-87960930
23 SDHB NM_003000.2(SDHB): c.32G> A (p.Arg11His) single nucleotide variant Conflicting interpretations of pathogenicity rs111430410 1:17380483-17380483 1:17053988-17053988
24 PIK3CA NM_006218.4(PIK3CA): c.327A> C (p.Glu109Asp) single nucleotide variant Uncertain significance rs1060500031 3:178916940-178916940 3:179199152-179199152
25 PIK3CA NM_006218.4(PIK3CA): c.1004_1005del (p.Arg335fs) deletion Uncertain significance rs1553821123 3:178921522-178921523 3:179203734-179203735
26 PIK3CA NM_006218.4(PIK3CA): c.995G> T (p.Ser332Ile) single nucleotide variant Uncertain significance rs1262394031 3:178921513-178921513 3:179203725-179203725
27 PIK3CA NM_006218.4(PIK3CA): c.1489A> C (p.Asn497His) single nucleotide variant Uncertain significance rs199563773 3:178928303-178928303 3:179210515-179210515
28 PIK3CA NM_006218.4(PIK3CA): c.1949T> C (p.Val650Ala) single nucleotide variant Uncertain significance rs1553823718 3:178937774-178937774 3:179219986-179219986
29 RINT1 NM_021930.6(RINT1): c.1447A> G (p.Met483Val) single nucleotide variant Uncertain significance rs869312982 7:105192130-105192130 7:105551683-105551683
30 RINT1 NM_021930.5(RINT1): c.1671_1671+2delTGT deletion Uncertain significance rs869312981 7:105195674-105195676 7:105555227-105555229
31 SDHB NM_003000.2(SDHB): c.559A> G (p.Ile187Val) single nucleotide variant Uncertain significance 1:17350551-17350551 1:17024056-17024056
32 PIK3CA NM_006218.4(PIK3CA): c.2975G> A (p.Arg992Gln) single nucleotide variant Uncertain significance 3:178951920-178951920 3:179234132-179234132
33 PIK3CA NM_006218.4(PIK3CA): c.470A> G (p.Asn157Ser) single nucleotide variant Uncertain significance 3:178917595-178917595 3:179199807-179199807
34 PIK3CA NM_006218.4(PIK3CA): c.623C> G (p.Thr208Ser) single nucleotide variant Uncertain significance 3:178919138-178919138 3:179201350-179201350
35 PIK3CA NM_006218.4(PIK3CA): c.2416+6G> A single nucleotide variant Uncertain significance 3:178942615-178942615 3:179224827-179224827
36 PIK3CA NM_006218.4(PIK3CA): c.563-3T> C single nucleotide variant Uncertain significance 3:178919075-178919075 3:179201287-179201287
37 PIK3CA NM_006218.4(PIK3CA): c.2524G> A (p.Gly842Ser) single nucleotide variant Uncertain significance 3:178947088-178947088 3:179229300-179229300
38 PIK3CA NM_006218.4(PIK3CA): c.29_53del (p.Leu10fs) deletion Uncertain significance 3:178916642-178916666 3:179198854-179198878
39 PIK3CA NM_006218.4(PIK3CA): c.214A> G (p.Ser72Gly) single nucleotide variant Uncertain significance 3:178916827-178916827 3:179199039-179199039
40 PIK3CA NM_006218.4(PIK3CA): c.817A> G (p.Ile273Val) single nucleotide variant Uncertain significance 3:178921335-178921335 3:179203547-179203547
41 PIK3CA NM_006218.4(PIK3CA): c.954G> A (p.Met318Ile) single nucleotide variant Uncertain significance 3:178921472-178921472 3:179203684-179203684
42 PIK3CA NM_006218.4(PIK3CA): c.1324G> C (p.Ala442Pro) single nucleotide variant Uncertain significance 3:178928046-178928046 3:179210258-179210258
43 PIK3CA NM_006218.4(PIK3CA): c.1597G> A (p.Ala533Thr) single nucleotide variant Uncertain significance 3:178936055-178936055 3:179218267-179218267
44 PIK3CA NM_006218.4(PIK3CA): c.2080G> T (p.Ala694Ser) single nucleotide variant Uncertain significance 3:178938838-178938838 3:179221050-179221050
45 PIK3CA NM_006218.4(PIK3CA): c.3194A> T (p.His1065Leu) single nucleotide variant Uncertain significance 3:178952139-178952139 3:179234351-179234351
46 PIK3CA NM_006218.4(PIK3CA): c.1747A> G (p.Met583Val) single nucleotide variant Uncertain significance rs1553823608 3:178937359-178937359 3:179219571-179219571
47 PIK3CA NM_006218.4(PIK3CA): c.2453G> A (p.Arg818His) single nucleotide variant Uncertain significance rs371049193 3:178943786-178943786 3:179225998-179225998
48 PIK3CA NM_006218.4(PIK3CA): c.211G> A (p.Val71Ile) single nucleotide variant Uncertain significance rs201269904 3:178916824-178916824 3:179199036-179199036
49 PIK3CA NM_006218.4(PIK3CA): c.742G> A (p.Gly248Ser) single nucleotide variant Uncertain significance rs1553820694 3:178919257-178919257 3:179201469-179201469
50 PIK3CA NM_006218.4(PIK3CA): c.178C> A (p.Gln60Lys) single nucleotide variant Uncertain significance rs71310379 3:178916791-178916791 3:179199003-179199003

Cosmic variations for Cowden Syndrome:

9
# Cosmic Mut ID Gene Symbol COSMIC Disease Classification
(Primary site, Site subtype, Primary histology, Histology subtype)
Mutation CDS Mutation AA GRCh38 Location Conf
1 COSM33765 AKT1 skin,neck,Overgrowth syndrome,Proteus syndrome c.49G>A p.E17K 14:104780214-104780214 4

Expression for Cowden Syndrome

Search GEO for disease gene expression data for Cowden Syndrome.

Pathways for Cowden Syndrome

Pathways related to Cowden Syndrome according to GeneCards Suite gene sharing:

(show all 36)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.83 TNS1 PTEN PIK3CA EGFR AKT1
2
Show member pathways
12.76 SMAD4 PTEN PIK3CA EGFR BRCA2 AKT1
3 12.71 SMAD4 PTEN PIK3CA EGFR BRCA2 AKT1
4
Show member pathways
12.61 PTEN PIK3CA EGFR BRCA2 AKT1
5
Show member pathways
12.51 SMAD4 PTEN PIK3CA EGFR BRCA2 AKT1
6
Show member pathways
12.42 PTEN PIK3CA EGFR AKT1
7 12.41 PTEN PIK3CA MIR21 MIR19A EGFR
8
Show member pathways
12.36 PIK3CA EGFR BMPR1A AKT1
9 12.22 PIK3CA MIR21 EGFR AKT1
10
Show member pathways
12.12 PTEN PIK3CA EGFR AKT1
11 12.05 PTEN PIK3CA EGFR AKT1
12
Show member pathways
12.05 PTEN PIK3CA EGFR AKT1
13
Show member pathways
12.02 PTEN PIK3CA EGFR AKT1
14 11.99 SMAD4 PIK3CA BMPR1A AKT1
15 11.87 PIK3CA EGFR AKT1
16
Show member pathways
11.85 SDHD SDHC SDHB
17 11.85 PIK3CA EGFR AKT1
18 11.83 SMAD4 PIK3CA AKT1
19 11.82 SMAD4 PTEN PIK3CA AKT1
20 11.79 PTEN PIK3CA AKT1
21 11.78 PTEN PIK3CA AKT1
22 11.66 SEC23B PIK3CA AKT1
23 11.61 PTEN PIK3CA AKT1
24 11.58 SMAD4 PTEN EGFR AKT1
25 11.5 PTEN PIK3CA AKT1
26 11.49 PTEN PIK3CA AKT1
27
Show member pathways
11.49 SMAD4 PIK3CA EGFR AKT1
28
Show member pathways
11.49 SMAD4 PTEN PIK3CA EGFR AKT1
29 11.45 PIK3CA EGFR AKT1
30 11.3 PTEN PIK3CA EGFR AKT1
31 11.29 SMAD4 PTEN EGFR BRCA2 BMPR1A AKT1
32 11.14 PIK3CA EGFR AKT1
33
Show member pathways
11.13 SMAD4 PIK3CA AKT1
34 11.09 PTEN PIK3CA AKT1
35 11.06 SMAD4 EGFR AKT1
36 10.71 PIK3CA EGFR AKT1

GO Terms for Cowden Syndrome

Cellular components related to Cowden Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 respiratory chain complex II GO:0045273 8.96 SDHC SDHB
2 mitochondrial respiratory chain complex II, succinate dehydrogenase complex (ubiquinone) GO:0005749 8.8 SDHD SDHC SDHB

Biological processes related to Cowden Syndrome according to GeneCards Suite gene sharing:

(show all 19)
# Name GO ID Score Top Affiliating Genes
1 negative regulation of apoptotic process GO:0043066 9.98 PTEN MIR21 MIR19A EGFR AKT1
2 intracellular signal transduction GO:0035556 9.88 TNS1 SMAD4 RASAL1 EGFR AKT1
3 positive regulation of transcription, DNA-templated GO:0045893 9.85 USF2 SMAD4 EGFR BRCA2 BMPR1A AKT1
4 cell proliferation GO:0008283 9.83 SMAD4 PTEN EGFR BRCA2 AKT1
5 transforming growth factor beta receptor signaling pathway GO:0007179 9.75 SMAD4 MIR21 BMPR1A
6 BMP signaling pathway GO:0030509 9.72 SMAD4 MIR21 BMPR1A
7 positive regulation of peptidyl-serine phosphorylation GO:0033138 9.71 PIK3CA EGFR AKT1
8 negative regulation of ERK1 and ERK2 cascade GO:0070373 9.67 SMAD4 PTEN MIR21
9 epidermal growth factor receptor signaling pathway GO:0007173 9.58 PIK3CA EGFR AKT1
10 negative regulation of macroautophagy GO:0016242 9.57 PIK3CA AKT1
11 positive regulation of SMAD protein signal transduction GO:0060391 9.56 SMAD4 BMPR1A
12 anoikis GO:0043276 9.52 PIK3CA AKT1
13 negative regulation of cell size GO:0045792 9.51 PTEN AKT1
14 mitochondrial electron transport, succinate to ubiquinone GO:0006121 9.46 SDHD SDHC
15 protein kinase B signaling GO:0043491 9.43 PTEN PIK3CA AKT1
16 cellular response to decreased oxygen levels GO:0036294 9.32 PTEN AKT1
17 response to UV-A GO:0070141 9.16 EGFR AKT1
18 tricarboxylic acid cycle GO:0006099 9.13 SDHD SDHC SDHB
19 regulation of signal transduction involved in mitotic G2 DNA damage checkpoint GO:1902504 8.62 RINT1 MIR21

Molecular functions related to Cowden Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 electron transfer activity GO:0009055 9.43 SDHD SDHC SDHB
2 nitric-oxide synthase regulator activity GO:0030235 9.16 EGFR AKT1
3 ubiquinone binding GO:0048039 8.96 SDHD SDHB
4 succinate dehydrogenase (ubiquinone) activity GO:0008177 8.8 SDHD SDHC SDHB

Sources for Cowden Syndrome

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
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