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 74 52 25 58 36 29 6 15 39
Multiple Hamartoma Syndrome 12 52 25 58
Cowden Disease 12 52 25 58
Lhermitte-Duclos Disease 12 74 52
Cowden's Disease 74 52 25
Mham 52 25
Cs 52 25
Cd 52 25
Dysplastic Gangliocytoma of the Cerebellum 52
Dysplastic Gangliocytoma of Cerebellum 12
Cowden's Syndrome 25

Characteristics:

Orphanet epidemiological data:

58
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:

Orphanet: 58  
Rare gastroenterological diseases
Rare skin diseases
Developmental anomalies during embryogenesis


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 Non-alcoholic fatty liver disease (NAFLD) and Endometrial cancer. The drugs Lactitol and Fluorodeoxyglucose F18 have been mentioned in the context of this disorder. Affiliated tissues include breast, thyroid and skin, and related phenotypes are generalized hyperkeratosis and palmoplantar keratoderma

Disease Ontology : 12 A syndrome 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 : 52 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 : 36 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 : 74 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 1116)
# Related Disease Score Top Affiliating Genes
1 cowden syndrome 1 35.2 TNS1 SMAD4 SDHB PTEN PIK3CA LYPD1
2 proteus syndrome 33.5 TNS1 PTEN PIK3CA LYPD1 AKT1
3 thyroid carcinoma 31.8 PTEN PIK3CA AKT1
4 endometrial cancer 31.7 SMAD4 PTEN PIK3CA EGFR CDKN3 BRCA2
5 kidney cancer 31.4 TNS1 SDHB PTEN PIK3CA MIR21 EGFR
6 leukemia, chronic lymphocytic 31.4 PTEN MIR21 MIR19A EGFR BRCA2 AKT1
7 neurofibromatosis, type iv, of riccardi 31.4 SDHD SDHC SDHB PTEN AKT1
8 bilateral breast cancer 31.3 PTEN PIK3CA BRCA2
9 meningioma, familial 31.3 PTEN KLLN EGFR AKT1
10 juvenile polyposis syndrome 31.2 SMAD4 PTEN LYPD1 BMPR1A
11 adenocarcinoma 31.2 SMAD4 PTEN PIK3CA EGFR BRCA2 AKT1
12 thyroid gland cancer 31.2 SDHB PTEN PIK3CA MIR21 EGFR CDKN3
13 lipomatosis 31.1 SDHB PTEN PIK3CA
14 peutz-jeghers syndrome 31.1 SMAD4 PTEN EGFR BRCA2
15 sarcoma 31.1 SDHD SDHC SDHB PIK3CA AKT1
16 breast ductal carcinoma 31.1 SMAD4 PTEN EGFR BRCA2
17 lynch syndrome 31.1 SMAD4 PTEN PIK3CA EGFR BRCA2 BMPR1A
18 leukemia, acute myeloid 31.0 PTEN MIR21 EGFR CDKN3 BRCA2 AKT1
19 endometrial adenocarcinoma 31.0 PTEN EGFR AKT1
20 glioblastoma multiforme 31.0 PTEN PIK3CA MIR21 EGFR CDKN3 BRCA2
21 squamous cell carcinoma 31.0 SMAD4 PTEN PIK3CA EGFR AKT1
22 renal cell carcinoma, nonpapillary 31.0 SDHC SDHB PTEN PIK3CA MIR21 EGFR
23 skin papilloma 30.9 PTEN EGFR AKT1
24 in situ carcinoma 30.9 PTEN EGFR BRCA2 AKT1
25 ductal carcinoma in situ 30.9 PTEN PIK3CA EGFR BRCA2 AKT1
26 oropharynx cancer 30.9 PTEN PIK3CA EGFR AKT1
27 carcinosarcoma 30.9 PTEN PIK3CA EGFR
28 hereditary paraganglioma-pheochromocytoma syndromes 30.9 SDHD SDHC SDHB
29 gastrointestinal stromal tumor 30.9 SDHD SDHC SDHB PTEN EGFR AKT1
30 uterine carcinosarcoma 30.9 PTEN PIK3CA EGFR AKT1
31 small cell cancer of the lung 30.8 PTEN PIK3CA MIR21 EGFR
32 glioma susceptibility 1 30.8 PTEN PIK3CA MIR21 EGFR
33 gastric adenocarcinoma 30.8 SMAD4 PTEN PIK3CA EGFR BMPR1A AKT1
34 lung adenoma 30.8 PTEN EGFR AKT1
35 glioma 30.8 PTEN PIK3CA MIR21 MIR19A EGFR BRCA2
36 sporadic breast cancer 30.8 PTEN EGFR BRCA2
37 suppression of tumorigenicity 12 30.8 SMAD4 PTEN PIK3CA EGFR BRCA2 AKT1
38 melanoma, uveal 30.7 SMAD4 PTEN EGFR AKT1
39 nasopharyngeal carcinoma 30.7 SMAD4 PTEN PIK3CA MIR21 EGFR AKT1
40 myeloma, multiple 30.7 PTEN MIR21 MIR19A EGFR AKT1
41 lymphoma, non-hodgkin, familial 30.6 PTEN PIK3CA MIR21 CDKN3 AKT1
42 cervical cancer 30.6 SMAD4 PTEN PIK3CA MIR21 EGFR AKT1
43 esophageal cancer 30.6 SMAD4 PTEN PIK3CA MIR21 EGFR CDKN3
44 hereditary breast ovarian cancer syndrome 30.6 PTEN BRCA2 BMPR1A
45 brain cancer 30.5 PTEN PIK3CA EGFR BRCA2 AKT1
46 obsolete: squamous cell carcinoma of head and neck 30.5 SMAD4 PTEN PIK3CA EGFR
47 ovarian disease 30.5 PTEN PIK3CA MIR21 EGFR BRCA2 AKT1
48 colon adenocarcinoma 30.5 SMAD4 PTEN PIK3CA MIR21 EGFR
49 von hippel-lindau syndrome 30.5 SDHD SDHC SDHB
50 pancreatic adenocarcinoma 30.5 SMAD4 PTEN PIK3CA MIR21 EGFR BRCA2

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:

58 31 (show top 50) (show all 57)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 generalized hyperkeratosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0005595
2 palmoplantar keratoderma 58 31 hallmark (90%) Very frequent (99-80%) HP:0000982
3 macule 58 31 hallmark (90%) Very frequent (99-80%) HP:0012733
4 papule 58 31 hallmark (90%) Very frequent (99-80%) HP:0200034
5 goiter 58 31 hallmark (90%) Very frequent (99-80%) HP:0000853
6 breast carcinoma 58 31 hallmark (90%) Very frequent (99-80%) HP:0003002
7 colorectal polyposis 58 31 hallmark (90%) Very frequent (99-80%) HP:0200063
8 papilloma 58 31 hallmark (90%) Very frequent (99-80%) HP:0012740
9 conjunctival hamartoma 58 31 hallmark (90%) Very frequent (99-80%) HP:0100780
10 macrocephaly 58 31 frequent (33%) Frequent (79-30%) HP:0000256
11 intellectual disability 58 31 frequent (33%) Frequent (79-30%) HP:0001249
12 ataxia 58 31 frequent (33%) Frequent (79-30%) HP:0001251
13 macroglossia 58 31 frequent (33%) Frequent (79-30%) HP:0000158
14 global developmental delay 58 31 frequent (33%) Frequent (79-30%) HP:0001263
15 cognitive impairment 58 31 frequent (33%) Frequent (79-30%) HP:0100543
16 subcutaneous nodule 58 31 frequent (33%) Frequent (79-30%) HP:0001482
17 cavernous hemangioma 58 31 frequent (33%) Frequent (79-30%) HP:0001048
18 mucosal telangiectasiae 58 31 frequent (33%) Frequent (79-30%) HP:0100579
19 melanocytic nevus 58 31 frequent (33%) Frequent (79-30%) HP:0000995
20 meningioma 58 31 frequent (33%) Frequent (79-30%) HP:0002858
21 abnormality of the penis 58 31 frequent (33%) Frequent (79-30%) HP:0000036
22 furrowed tongue 58 31 frequent (33%) Frequent (79-30%) HP:0000221
23 hamartomatous polyposis 58 31 frequent (33%) Frequent (79-30%) HP:0004390
24 adenoma sebaceum 58 31 frequent (33%) Frequent (79-30%) HP:0009720
25 lipoma 58 31 frequent (33%) Frequent (79-30%) HP:0012032
26 pectus excavatum 58 31 occasional (7.5%) Occasional (29-5%) HP:0000767
27 seizures 58 31 occasional (7.5%) Occasional (29-5%) HP:0001250
28 failure to thrive 58 31 occasional (7.5%) Occasional (29-5%) HP:0001508
29 scoliosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0002650
30 kyphosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0002808
31 high palate 58 31 occasional (7.5%) Occasional (29-5%) HP:0000218
32 hearing impairment 58 31 occasional (7.5%) Occasional (29-5%) HP:0000365
33 cataract 58 31 occasional (7.5%) Occasional (29-5%) HP:0000518
34 increased intracranial pressure 58 31 occasional (7.5%) Occasional (29-5%) HP:0002516
35 brachydactyly 58 31 occasional (7.5%) Occasional (29-5%) HP:0001156
36 short stature 58 31 occasional (7.5%) Occasional (29-5%) HP:0004322
37 hypopigmented skin patches 58 31 occasional (7.5%) Occasional (29-5%) HP:0001053
38 autism 58 31 occasional (7.5%) Occasional (29-5%) HP:0000717
39 myopia 58 31 occasional (7.5%) Occasional (29-5%) HP:0000545
40 melanoma 58 31 occasional (7.5%) Occasional (29-5%) HP:0002861
41 renal cell carcinoma 58 31 occasional (7.5%) Occasional (29-5%) HP:0005584
42 cellular immunodeficiency 58 31 occasional (7.5%) Occasional (29-5%) HP:0005374
43 multiple cafe-au-lait spots 58 31 occasional (7.5%) Occasional (29-5%) HP:0007565
44 gynecomastia 58 31 occasional (7.5%) Occasional (29-5%) HP:0000771
45 enlarged polycystic ovaries 58 31 occasional (7.5%) Occasional (29-5%) HP:0008675
46 abnormal cerebellum morphology 58 31 occasional (7.5%) Occasional (29-5%) HP:0001317
47 follicular thyroid carcinoma 58 31 occasional (7.5%) Occasional (29-5%) HP:0006731
48 bone cyst 58 31 occasional (7.5%) Occasional (29-5%) HP:0012062
49 endometrial carcinoma 58 31 occasional (7.5%) Occasional (29-5%) HP:0012114
50 neoplasm 58 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 (show all 37)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability GR00055-A-2 10.54 EGFR PIK3CA
2 Decreased viability GR00221-A-1 10.54 AKT1 BMPR1A EGFR PIK3CA SDHD
3 Decreased viability GR00221-A-2 10.54 AKT1 BMPR1A PIK3CA SDHD
4 Decreased viability GR00221-A-3 10.54 AKT1 BMPR1A
5 Decreased viability GR00221-A-4 10.54 AKT1 BMPR1A EGFR PIK3CA SDHD
6 Decreased viability GR00381-A-1 10.54 SDHD
7 Decreased viability GR00402-S-2 10.54 AKT1 BMPR1A EGFR PIK3CA SDHD
8 Increased shRNA abundance (Z-score > 2) GR00366-A-107 9.9 SMAD4
9 Increased shRNA abundance (Z-score > 2) GR00366-A-151 9.9 PTEN
10 Increased shRNA abundance (Z-score > 2) GR00366-A-152 9.9 PTEN
11 Increased shRNA abundance (Z-score > 2) GR00366-A-157 9.9 PIK3CA
12 Increased shRNA abundance (Z-score > 2) GR00366-A-16 9.9 AKT1 PIK3CA PTEN
13 Increased shRNA abundance (Z-score > 2) GR00366-A-166 9.9 PIK3CA
14 Increased shRNA abundance (Z-score > 2) GR00366-A-168 9.9 PTEN
15 Increased shRNA abundance (Z-score > 2) GR00366-A-177 9.9 AKT1 PIK3CA
16 Increased shRNA abundance (Z-score > 2) GR00366-A-182 9.9 USF2
17 Increased shRNA abundance (Z-score > 2) GR00366-A-190 9.9 PIK3CA
18 Increased shRNA abundance (Z-score > 2) GR00366-A-21 9.9 SMAD4
19 Increased shRNA abundance (Z-score > 2) GR00366-A-214 9.9 PTEN
20 Increased shRNA abundance (Z-score > 2) GR00366-A-25 9.9 SMAD4
21 Increased shRNA abundance (Z-score > 2) GR00366-A-35 9.9 USF2
22 Increased shRNA abundance (Z-score > 2) GR00366-A-42 9.9 AKT1 PIK3CA PTEN SMAD4 USF2
23 Increased shRNA abundance (Z-score > 2) GR00366-A-43 9.9 SMAD4
24 Increased shRNA abundance (Z-score > 2) GR00366-A-46 9.9 SMAD4
25 Increased shRNA abundance (Z-score > 2) GR00366-A-49 9.9 PIK3CA
26 Increased shRNA abundance (Z-score > 2) GR00366-A-50 9.9 AKT1
27 Increased shRNA abundance (Z-score > 2) GR00366-A-54 9.9 SMAD4
28 Increased shRNA abundance (Z-score > 2) GR00366-A-60 9.9 AKT1 PIK3CA
29 Increased shRNA abundance (Z-score > 2) GR00366-A-63 9.9 PTEN USF2
30 Increased shRNA abundance (Z-score > 2) GR00366-A-70 9.9 AKT1
31 Increased shRNA abundance (Z-score > 2) GR00366-A-73 9.9 SMAD4
32 Increased shRNA abundance (Z-score > 2) GR00366-A-74 9.9 SMAD4
33 Increased shRNA abundance (Z-score > 2) GR00366-A-81 9.9 SMAD4
34 Increased shRNA abundance (Z-score > 2) GR00366-A-85 9.9 AKT1 USF2
35 Increased shRNA abundance (Z-score > 2) GR00366-A-93 9.9 PTEN
36 Decreased sensitivity to paclitaxel GR00112-A-0 9.26 PTEN SMAD4
37 Increased mitotic index GR00110-A-0 9.26 BMPR1A SDHD SMAD4 TNS1

MGI Mouse Phenotypes related to Cowden Syndrome:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 10.18 AKT1 BMPR1A BRCA2 CDKN3 LYPD1 PIK3CA
2 mortality/aging MP:0010768 10.07 AKT1 BMPR1A BRCA2 EGFR PIK3CA PTEN
3 endocrine/exocrine gland MP:0005379 10.02 AKT1 BMPR1A BRCA2 EGFR PIK3CA PTEN
4 neoplasm MP:0002006 9.81 AKT1 BMPR1A BRCA2 EGFR PIK3CA PTEN
5 nervous system MP:0003631 9.7 AKT1 BMPR1A BRCA2 EGFR LYPD1 PIK3CA
6 normal MP:0002873 9.36 AKT1 BMPR1A BRCA2 EGFR PTEN SDHB

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
4 Cola 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 Sirolimus for Cowden Syndrome With Colon Polyposis Recruiting NCT04094675 Phase 2 Sirolimus
4 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
5 Open Label Phase II Study of Everolimus (RAD001) in Patients With Segmental Overgrowth Syndrome Withdrawn NCT02569125 Phase 2 Everolimus
6 Eculizumab in HELLP Syndrome Not yet recruiting NCT04103489 Phase 1 Eculizumab
7 Clinical, Genetic, Behavioral, Laboratory and Epidemiologic Characterization of Individuals and Families at High Risk of Breast/Ovarian Cancer Completed NCT00040222
8 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:

40
Breast, Thyroid, Skin, Kidney, Cerebellum, Uterus, Brain

Publications for Cowden Syndrome

Articles related to Cowden Syndrome:

(show top 50) (show all 675)
# Title Authors PMID Year
1
Germline Heterozygous Variants in SEC23B Are Associated with Cowden Syndrome and Enriched in Apparently Sporadic Thyroid Cancer. 61 6
26522472 2015
2
Genetic/familial high-risk assessment: breast and ovarian, version 1.2014. 61 6
25190698 2014
3
Germline PIK3CA and AKT1 mutations in Cowden and Cowden-like syndromes. 61 6
23246288 2013
4
Succinate dehydrogenase gene variants and their role in Cowden syndrome. 61 6
21565294 2011
5
Germline epigenetic regulation of KILLIN in Cowden and Cowden-like syndrome. 61 6
21177507 2010
6
Germline mutations and variants in the succinate dehydrogenase genes in Cowden and Cowden-like syndromes. 61 6
18678321 2008
7
Clinical genetics evaluation in identifying the etiology of autism spectrum disorders: 2013 guideline revisions. 6
23519317 2013
8
The first Dutch SDHB founder deletion in paraganglioma-pheochromocytoma patients. 6
19368708 2009
9
Differential expression of PTEN-targeting microRNAs miR-19a and miR-21 in Cowden syndrome. 61 46
18460397 2008
10
Absence of somatic SDHD mutations in sporadic neuroendocrine tumors and detection of two germline variants in paraganglioma patients. 6
12386824 2002
11
Identification of novel SDHD mutations in patients with phaeochromocytoma and/or paraganglioma. 6
12111639 2002
12
Alterations of the SDHD gene locus in midgut carcinoids, Merkel cell carcinomas, pheochromocytomas, and abdominal paragangliomas. 6
12007193 2002
13
Germline SDHD mutation in paraganglioma of the spinal cord. 6
11526495 2001
14
Somatic and occult germ-line mutations in SDHD, a mitochondrial complex II gene, in nonfamilial pheochromocytoma. 6
11156372 2000
15
Mutations in SDHD, a mitochondrial complex II gene, in hereditary paraganglioma. 6
10657297 2000
16
Pacinian collagenoma: A distinct form of sclerotic fibroma. 61
31606915 2020
17
BRCA and Beyond: Comprehensive Image-rich Review of Hereditary Breast and Gynecologic Cancer Syndromes. 61
32031911 2020
18
An update on the CNS manifestations of brain tumor polyposis syndromes. 61
31970492 2020
19
Genome sequencing analysis of a family with a child displaying severe abdominal distention and recurrent hypoglycemia. 61
31971667 2020
20
Multiple Eyelid Neoplasms in Cowden Syndrome. 61
31923094 2020
21
The Clinical Spectrum of PTEN Mutations. 61
31433956 2020
22
Endometrial Endometrioid Carcinoma With Ovarian Metastasis Showing Morula-like Features in a Patient With Cowden Syndrome: A Case Report. 61
30676432 2020
23
Resection of a Symptomatic Dysplastic Cerebellar Gangliocytoma: 2-Dimensional Operative Video. 61
31807781 2019
24
Hereditary Cancer Syndromes and Risk Assessment: ACOG COMMITTEE OPINION SUMMARY, Number 793. 61
31764755 2019
25
Hereditary Cancer Syndromes and Risk Assessment: ACOG COMMITTEE OPINION, Number 793. 61
31764758 2019
26
Gingival Papillomatosis as the Oral Sign of Cowden Syndrome: A Case Report. 61
31969239 2019
27
Thyroid Tumors You Don't Want to Miss. 61
31672297 2019
28
PTEN Hamartoma tumor syndrome in childhood: A review of the clinical literature. 61
31609537 2019
29
Imaging of PTEN-related abnormalities in the central nervous system. 61
31927175 2019
30
Spectrum of gastrointestinal tract pathology in a multicenter cohort of 43 Cowden syndrome patients. 61
31273317 2019
31
A Pilot Study of Sirolimus in Subjects with Cowden Syndrome or Other Syndromes Characterized by Germline Mutations in PTEN. 61
31350329 2019
32
Signet ring cell variant of follicular thyroid carcinoma: Report of two cases with focus on morphological, expressional and genetic characteristics. 61
31699114 2019
33
Mystery Case: Cowden syndrome presenting with paraneoplastic encephalitis. 61
31659132 2019
34
Cowden syndrome: gastrointestinal manifestations of an infrequent polyposis. 61
31096272 2019
35
Metachronous ovarian endometrioid carcinomas in a patient with a PTEN variant: case report of incidentally detected Cowden syndrome. 61
31664961 2019
36
Distinct Alterations in Tricarboxylic Acid Cycle Metabolites Associate with Cancer and Autism Phenotypes in Cowden Syndrome and Bannayan-Riley-Ruvalcaba Syndrome. 61
31564436 2019
37
Toward Systems Pathology for PTEN Diagnostics. 61
31615872 2019
38
Clinical, Imaging, and Pathologic Features of Conditions with Combined Esophageal and Cutaneous Manifestations. 61
31419189 2019
39
Hereditary Gastrointestinal Cancer Syndromes: Role of Imaging in Screening, Diagnosis, and Management. 61
31373866 2019
40
Intramucosal fat is uncommon in large bowel polyps but raises three differential diagnoses. 61
31097491 2019
41
Bilateral Recurrent Dysplastic Cerebellar Gangliocytoma (Lhermitte-Duclos Disease) in Cowden Syndrome: A Case Report and Literature Review. 61
30905649 2019
42
Left atrial cavernous haemangioma presenting with cardiac tamponade in a patient with Cowden syndrome. 61
31289165 2019
43
Enlarging left atrial haemangioma in a patient with Cowden syndrome. 61
31352392 2019
44
Letter to the Editor Regarding "Giant Cerebral Aneurysm in a Patient with Cowden Syndrome Treated with Surgical Clipping". 61
31266126 2019
45
In Reply to the Letter to Editor Regarding "Giant Cerebral Aneurysm in a Patient with Cowden Syndrome Treated with Surgical Clipping". 61
31266127 2019
46
Giant Cerebral Aneurysm in a Patient with Cowden Syndrome Treated with Surgical Clipping. 61
30904793 2019
47
Is Malignant Germ-Cell Tumor Associated With Cowden Syndrome? 61
30733184 2019
48
Cowden syndrome caused by a novel mutation: Endoscopy aided diagnosis. 61
30952542 2019
49
PTEN Hamartoma Tumor Syndrome: A Clinical Overview. 61
31216739 2019
50
Current Knowledge of Germline Genetic Risk Factors for the Development of Non-Medullary Thyroid Cancer. 61
31247975 2019

Variations for Cowden Syndrome

ClinVar genetic disease variations for Cowden Syndrome:

6 (show top 50) (show all 125) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 PTEN NM_000314.7(PTEN):c.406T>C (p.Cys136Arg)SNV Pathogenic 183726 rs786201044 10:89692922-89692922 10:87933165-87933165
2 PIK3CA NM_006218.4(PIK3CA):c.3129G>T (p.Met1043Ile)SNV Pathogenic 217292 rs121913283 3:178952074-178952074 3:179234286-179234286
3 PTEN NM_000314.7(PTEN):c.118G>T (p.Glu40Ter)SNV Pathogenic 224545 rs869312778 10:89653820-89653820 10:87894063-87894063
4 PTEN NM_001304718.2(PTEN):c.-327deldeletion Pathogenic 224546 rs869312779 10:89692940-89692940 10:87933183-87933183
5 PTEN NM_000314.7(PTEN):c.765_766AG[1] (p.Glu256fs)short repeat Pathogenic 224547 rs869312780 10:89717740-89717741 10:87957983-87957984
6 PTEN NM_000314.7(PTEN):c.697C>T (p.Arg233Ter)SNV Pathogenic 7813 rs121909219 10:89717672-89717672 10:87957915-87957915
7 PIK3CA NM_006218.4(PIK3CA):c.1133G>A (p.Cys378Tyr)SNV Pathogenic 39704 rs397514565 3:178922364-178922364 3:179204576-179204576
8 PIK3CA NM_006218.4(PIK3CA):c.3139C>T (p.His1047Tyr)SNV Pathogenic 39705 rs121913281 3:178952084-178952084 3:179234296-179234296
9 SDHB NM_003000.2(SDHB):c.591del (p.Ser198fs)deletion Pathogenic 412462 rs1060503757 1:17350519-17350519 1:17024024-17024024
10 PIK3CA NM_006218.4(PIK3CA):c.1093G>A (p.Glu365Lys)SNV Pathogenic 419222 rs1064793732 3:178922324-178922324 3:179204536-179204536
11 PIK3CA NM_006218.4(PIK3CA):c.3129G>A (p.Met1043Ile)SNV Pathogenic/Likely pathogenic 179173 rs121913283 3:178952074-178952074 3:179234286-179234286
12 PIK3CA NM_006218.4(PIK3CA):c.1030G>A (p.Val344Met)SNV Pathogenic/Likely pathogenic 376498 rs1057519942 3:178921548-178921548 3:179203760-179203760
13 PTEN NM_000314.7(PTEN):c.486C>G (p.Asp162Glu)SNV Likely pathogenic 224544 rs869312777 10:89693002-89693002 10:87933245-87933245
14 PTEN NM_000314.7(PTEN):c.344A>G (p.Asp115Gly)SNV Likely pathogenic 224542 rs869312775 10:89692860-89692860 10:87933103-87933103
15 PTEN NM_000314.7(PTEN):c.408T>G (p.Cys136Trp)SNV Likely pathogenic 224543 rs869312776 10:89692924-89692924 10:87933167-87933167
16 PTEN NM_000314.8(PTEN):c.1023del (p.Phe341fs)deletion Likely pathogenic 623215 rs1564568689 10:89720869-89720869 10:87961112-87961112
17 SDHB NM_003000.2(SDHB):c.8C>G (p.Ala3Gly)SNV Conflicting interpretations of pathogenicity 12791 rs11203289 1:17380507-17380507 1:17054012-17054012
18 SDHB NM_003000.2(SDHB):c.487T>C (p.Ser163Pro)SNV Conflicting interpretations of pathogenicity 12792 rs33927012 1:17354297-17354297 1:17027802-17027802
19 SDHB NM_003000.2(SDHB):c.32G>A (p.Arg11His)SNV Conflicting interpretations of pathogenicity 36768 rs111430410 1:17380483-17380483 1:17053988-17053988
20 SDHB NM_003000.2(SDHB):c.650G>A (p.Arg217His)SNV Conflicting interpretations of pathogenicity 412491 rs747518441 1:17349218-17349218 1:17022723-17022723
21 SDHB NM_003000.2(SDHB):c.200+7A>GSNV Conflicting interpretations of pathogenicity 239424 rs371329778 1:17371249-17371249 1:17044754-17044754
22 PIK3CA NM_006218.4(PIK3CA):c.*29T>CSNV Conflicting interpretations of pathogenicity 246606 rs141178472 3:178952181-178952181 3:179234393-179234393
23 PTEN NM_000314.7(PTEN):c.838A>G (p.Ile280Val)SNV Conflicting interpretations of pathogenicity 468719 rs1474354667 10:89720687-89720687 10:87960930-87960930
24 PIK3CA NM_006218.4(PIK3CA):c.742G>A (p.Gly248Ser)SNV Uncertain significance 523491 rs1553820694 3:178919257-178919257 3:179201469-179201469
25 PIK3CA NM_006218.4(PIK3CA):c.178C>A (p.Gln60Lys)SNV Uncertain significance 526635 rs71310379 3:178916791-178916791 3:179199003-179199003
26 PIK3CA NM_006218.4(PIK3CA):c.141T>G (p.His47Gln)SNV Uncertain significance 456528 rs768265254 3:178916754-178916754 3:179198966-179198966
27 PIK3CA NM_006218.4(PIK3CA):c.466C>T (p.Leu156Phe)SNV Uncertain significance 456547 rs201705993 3:178917591-178917591 3:179199803-179199803
28 PIK3CA NM_006218.4(PIK3CA):c.931A>G (p.Ile311Val)SNV Uncertain significance 526636 rs201238717 3:178921449-178921449 3:179203661-179203661
29 PIK3CA NM_006218.4(PIK3CA):c.995G>T (p.Ser332Ile)SNV Uncertain significance 526639 rs1262394031 3:178921513-178921513 3:179203725-179203725
30 PIK3CA NM_006218.4(PIK3CA):c.386A>G (p.Asp129Gly)SNV Uncertain significance 526634 rs1553820490 3:178917511-178917511 3:179199723-179199723
31 PIK3CA NM_006218.4(PIK3CA):c.2651A>G (p.Lys884Arg)SNV Uncertain significance 526637 rs1395235750 3:178947215-178947215 3:179229427-179229427
32 PIK3CA NM_006218.4(PIK3CA):c.436G>A (p.Val146Ile)SNV Uncertain significance 526641 rs755969956 3:178917561-178917561 3:179199773-179199773
33 PIK3CA NM_006218.4(PIK3CA):c.560A>C (p.Lys187Thr)SNV Uncertain significance 526638 rs1553820520 3:178917685-178917685 3:179199897-179199897
34 PIK3CA NM_006218.4(PIK3CA):c.361A>G (p.Ile121Val)SNV Uncertain significance 246688 rs371727887 3:178917486-178917486 3:179199698-179199698
35 PIK3CA NM_006218.4(PIK3CA):c.1490A>G (p.Asn497Ser)SNV Uncertain significance 246681 rs753879573 3:178928304-178928304 3:179210516-179210516
36 PIK3CA NM_006218.4(PIK3CA):c.2016-3T>CSNV Uncertain significance 246682 rs879254354 3:178938771-178938771 3:179220983-179220983
37 SDHB NM_003000.2(SDHB):c.112C>T (p.Arg38Cys)SNV Uncertain significance 371801 rs202119350 1:17371344-17371344 1:17044849-17044849
38 PIK3CA NM_006218.4(PIK3CA):c.317G>T (p.Gly106Val)SNV Uncertain significance 376479 rs1057519930 3:178916930-178916930 3:179199142-179199142
39 SDHB NM_003000.2(SDHB):c.721T>G (p.Tyr241Asp)SNV Uncertain significance 412464 rs1060503758 1:17349147-17349147 1:17022652-17022652
40 SDHB NM_003000.2(SDHB):c.307A>G (p.Met103Val)SNV Uncertain significance 239429 rs140178341 1:17355211-17355211 1:17028716-17028716
41 PIK3CA NM_006218.4(PIK3CA):c.1747A>G (p.Met583Val)SNV Uncertain significance 456533 rs1553823608 3:178937359-178937359 3:179219571-179219571
42 PIK3CA NM_006218.4(PIK3CA):c.2453G>A (p.Arg818His)SNV Uncertain significance 456540 rs371049193 3:178943786-178943786 3:179225998-179225998
43 PIK3CA NM_006218.4(PIK3CA):c.154G>C (p.Glu52Gln)SNV Uncertain significance 456530 rs1553820355 3:178916767-178916767 3:179198979-179198979
44 PIK3CA NM_006218.4(PIK3CA):c.321_323del (p.Arg108del)deletion Uncertain significance 456545 rs1553820399 3:178916934-178916936 3:179199146-179199148
45 PIK3CA NM_006218.4(PIK3CA):c.400C>T (p.Pro134Ser)SNV Uncertain significance 456546 rs750545881 3:178917525-178917525 3:179199737-179199737
46 PIK3CA NM_006218.4(PIK3CA):c.1528C>A (p.His510Asn)SNV Uncertain significance 456529 rs199747934 3:178928342-178928342 3:179210554-179210554
47 PIK3CA NM_006218.4(PIK3CA):c.2728A>G (p.Ile910Val)SNV Uncertain significance 456542 rs1553825421 3:178947853-178947853 3:179230065-179230065
48 PIK3CA NM_006218.4(PIK3CA):c.2915C>T (p.Thr972Ile)SNV Uncertain significance 456544 rs1553825480 3:178948143-178948143 3:179230355-179230355
49 PIK3CA NM_006218.4(PIK3CA):c.211G>A (p.Val71Ile)SNV Uncertain significance 456536 rs201269904 3:178916824-178916824 3:179199036-179199036
50 SDHB NM_003000.2(SDHB):c.440A>G (p.Tyr147Cys)SNV Uncertain significance 412466 rs774568101 1:17354344-17354344 1:17027849-17027849

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 COSM133535772 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 KEGG:

36
# Name Kegg Source Accession
1 Non-alcoholic fatty liver disease (NAFLD) hsa04932

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

(show all 29)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.75 SMAD4 PTEN PIK3CA EGFR BRCA2 AKT1
2 12.71 SMAD4 PTEN PIK3CA EGFR BRCA2 AKT1
3
Show member pathways
12.59 PTEN PIK3CA EGFR BRCA2 AKT1
4
Show member pathways
12.51 SMAD4 PTEN PIK3CA EGFR BRCA2 AKT1
5 12.43 PTEN PIK3CA MIR21 MIR19A EGFR
6
Show member pathways
12.36 PIK3CA EGFR BMPR1A AKT1
7 12.26 SMAD4 PTEN PIK3CA AKT1
8 12.22 PIK3CA MIR21 EGFR AKT1
9
Show member pathways
12.05 PTEN PIK3CA EGFR AKT1
10
Show member pathways
12.02 PTEN PIK3CA EGFR AKT1
11 11.99 SMAD4 PIK3CA BMPR1A AKT1
12 11.82 SMAD4 PTEN PIK3CA AKT1
13 11.78 PTEN PIK3CA AKT1
14 11.78 PTEN PIK3CA AKT1
15 11.66 SEC23B PIK3CA AKT1
16 11.61 PTEN PIK3CA AKT1
17 11.58 SMAD4 PTEN EGFR AKT1
18 11.5 PTEN PIK3CA AKT1
19 11.49 PTEN PIK3CA AKT1
20
Show member pathways
11.49 SMAD4 PIK3CA EGFR AKT1
21
Show member pathways
11.49 SMAD4 PTEN PIK3CA EGFR AKT1
22 11.45 PIK3CA EGFR AKT1
23 11.3 PTEN PIK3CA EGFR AKT1
24 11.29 SMAD4 PTEN EGFR BRCA2 BMPR1A AKT1
25 11.14 PIK3CA EGFR AKT1
26
Show member pathways
11.13 SMAD4 PIK3CA AKT1
27 11.09 PTEN PIK3CA AKT1
28 11.06 SMAD4 EGFR AKT1
29 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 24)
# Name GO ID Score Top Affiliating Genes
1 negative regulation of apoptotic process GO:0043066 10 PTEN MIR21 MIR19A EGFR AKT1
2 intracellular signal transduction GO:0035556 9.95 TNS1 SMAD4 RASAL1 EGFR AKT1
3 cellular response to insulin stimulus GO:0032869 9.79 USF1 PTEN AKT1
4 BMP signaling pathway GO:0030509 9.77 SMAD4 MIR21 BMPR1A
5 positive regulation of peptidyl-serine phosphorylation GO:0033138 9.77 PIK3CA EGFR AKT1
6 negative regulation of ERK1 and ERK2 cascade GO:0070373 9.73 SMAD4 PTEN MIR21
7 cellular response to growth factor stimulus GO:0071363 9.71 EGFR BMPR1A AKT1
8 glucose metabolic process GO:0006006 9.69 USF1 PIK3CA AKT1
9 epidermal growth factor receptor signaling pathway GO:0007173 9.65 PIK3CA EGFR AKT1
10 negative regulation of macroautophagy GO:0016242 9.61 PIK3CA AKT1
11 positive regulation of SMAD protein signal transduction GO:0060391 9.58 SMAD4 BMPR1A
12 anoikis GO:0043276 9.58 PIK3CA AKT1
13 protein kinase B signaling GO:0043491 9.58 PTEN PIK3CA AKT1
14 negative regulation of cell size GO:0045792 9.57 PTEN AKT1
15 tricarboxylic acid cycle GO:0006099 9.54 SDHD SDHC SDHB
16 mesendoderm development GO:0048382 9.52 SMAD4 BMPR1A
17 mitochondrial electron transport, succinate to ubiquinone GO:0006121 9.49 SDHD SDHC
18 cellular response to decreased oxygen levels GO:0036294 9.46 PTEN AKT1
19 late viral transcription GO:0019086 9.43 USF2 USF1
20 cell proliferation GO:0008283 9.35 SMAD4 PTEN EGFR BRCA2 AKT1
21 response to UV-A GO:0070141 9.32 EGFR AKT1
22 positive regulation of transcription from RNA polymerase II promoter by glucose GO:0000432 9.26 USF2 USF1
23 positive regulation of transcription, DNA-templated GO:0045893 9.17 USF2 USF1 SMAD4 EGFR BRCA2 BMPR1A
24 regulation of transcription from RNA polymerase II promoter by glucose GO:0000430 9.16 USF2 USF1

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 9.5 SDHD SDHC SDHB
2 ubiquinone binding GO:0048039 9.26 SDHD SDHB
3 nitric-oxide synthase regulator activity GO:0030235 9.16 EGFR AKT1
4 succinate dehydrogenase (ubiquinone) activity GO:0008177 8.96 SDHD SDHB
5 succinate dehydrogenase activity GO:0000104 8.62 SDHD SDHC

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 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
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48 NCI
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50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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