Cowden disease

カウデン症候群

WordNet

1. an impairment of health or a condition of abnormal functioning
2. caused by or altered by or manifesting disease or pathology; "diseased tonsils"; "a morbid growth"; "pathologic tissue"; "pathological bodily processes" (同)morbid, pathologic, pathological

PrepTutorEJDIC

1. (体の)『病気』,疾患 / (精神・道徳などの)病気,病弊
2. 女性の話術芸人 =diseur
3. 病気にかかった / 病的な,不健全な(morbid)

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/09/17 16:31:24」(JST)

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Cowden syndrome
Classification and external resources
ICD-9-CM	759.6
OMIM	158350
DiseasesDB	31336
eMedicine	derm/86
MeSH	D006223

Cowden syndrome (also known as "Cowden's disease," and "Multiple hamartoma syndrome") is a rare autosomal dominant inherited disorder characterized by multiple tumor-like growths called hamartomas and an increased risk of certain forms of cancer.

Cowden syndrome is associated with mutations in PTEN, a tumor suppressor gene, that cause the PTEN protein not to work properly leading to hyperactivity of the mTOR pathway. These mutations lead to characteristic features including macrocephaly, intestinal hamartomatous polyps, benign skin tumors (multiple trichilemmomas, papillomatous papules, and acral keratoses) and dysplastic gangliocytoma of the cerebellum (Lhermitte-Duclos disease). In addition, there is a predisposition to breast carcinoma, follicular carcinoma of the thyroid, and endometrial carcinoma.

Signs and symptoms

See also: List of cutaneous neoplasms associated with systemic syndromes

Clinical features of Cowden syndrome are diverse, including breast, endometrial, thyroid, kidney and colorectal cancers, dermatologic features such as oral and skin papillomas, trichilemmomas, gastrointestinal features such as mixed polyposis including hamartomas, and neurologic features such as Lhermitte–Duclos disease. Diagnostic criteria have evolved over the years; the most recent is the Cleveland Clinic scoring system in 2011 derived from 3,042 probands. For an individual patient, these features may be evaluated by the Cleveland Clinic web calculator to derive an individual probability of a relevant gene mutation.

The characteristic hamartomas of Cowden syndrome are small, noncancerous growths that are most commonly found on the skin and mucous membranes (such as the lining of the mouth and nose), but can also occur in the intestinal tract and other parts of the body. They are largely benign. However, people with Cowden syndrome have an increased risk of developing several types of cancer, including cancers of the breast, thyroid, and uterus.

Up to 75% have benign breast conditions such as ductal hyperplasia, intraductal papillomatosis, adenosis, lobular atrophy, fibroadenomas, and fibrocystic changes. Nonmedullary thyroid cancer develops in up to 10 percent of affected individuals. In addition, over one-half of those affected have follicular adenomas or multinodular goiter of the thyroid. Other malignancies that appear to be associated with Cowden and Cowden-like syndrome include endometrial and renal cancers. Other signs and symptoms of Cowden syndrome can include an enlarged head, a rare noncancerous brain tumor called Lhermitte-Duclos disease, and glycogenic acanthosis of the esophagus. The majority of affected individuals develop the characteristic skin lesions by age 20.

A 2010 review of 211 patients (21 from one center, and the remaining 190 from the external literature) studied the risks for cancer and Lhermitte-Duclos disease in Cowden syndrome patients.

Cumulative risk of any cancer diagnosis in female (red) and male (blue) patients with Cowden syndrome from birth to age 70 (Kaplan-Meier).

The cumulative lifetime (age 70 years) risks were 89% for any cancer diagnosis (95% confidence interval (CI) = 80%,95%), breast cancer [female] 81% (CI = 66%,90%), LDD 32% (CI = 19%,49%), thyroid cancer 21% (CI = 14%,29%), endometrial cancer 19% (CI = 10%,32%) and renal cancer 15% (CI = 6%,32%). A previously unreported increased lifetime risk for colorectal cancer was identified (16%, CI = 8%,24%). Male CS patients had fewer cancers diagnosed than female patients and often had cancers not classically associated with CS.

Genetics

Mutations in the PTEN gene cause Cowden syndrome. PTEN is a tumor suppressor gene, which means it helps control the growth and division of cells. Inherited mutations in the PTEN gene have been found in about 80 percent of people with Cowden syndrome. These mutations prevent the PTEN protein from effectively regulating cell survival and division, which can lead to the formation of tumors. Cowden syndrome is one of several inherited diseases caused by mutations in the PTEN gene.

In the other 20 percent of Cowden syndrome cases, the cause is not yet known. Some of these cases may be caused by mutations in a region of DNA that regulates the activity of the PTEN gene. Others may have mutations in certain subunits of succinate dehydrogenase, a mitochondrial enzyme. Recently, methylation of the KILLIN gene has also been reported in patients with similar clinical features.

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In some cases, an affected person inherits the mutation from one affected parent. Other cases may result from new ("de novo") mutations in the gene. These cases occur in people with no history of the disorder in their family. It is characterized by numerous hamartomas, among other symptoms.

Treatment

Patients are usually managed by a multidisciplinary team including surgeons, gynecologists, and dermatologists because of the complex nature of this disorder. Follow-up for the increased risk of breast cancer risk includes monthly breast self-examination, annual breast examination, and mammography at age 30 or five years earlier than the youngest age of breast cancer in the family. The magnitude of the risk of breast cancer justifies routine screening with breast MRI as per published guidelines.

Epidemiology

Because Cowden syndrome can be difficult to diagnose, the exact prevalence is unknown; however, it probably occurs in at least 1 in 200,000 people.

History

Cowden syndrome was first described in 1963 by Lloyd & Dennis. They named the condition after the surname of the patient.

See also

• List of cutaneous neoplasms associated with systemic syndromes

References

Notes

• de Jong MM, Nolte IM, te Meerman GJ, van der Graaf WT, Oosterwijk JC, Kleibeuker JH, Schaapveld M, de Vries EG (2002). "Genes other than BRCA1 and BRCA2 involved in breast cancer susceptibility". J Med Genet 39 (4): 225–42. doi:10.1136/jmg.39.4.225. PMC 1735082. PMID 11950848. 
• Eng C (2000). "Will the real Cowden syndrome please stand up: revised diagnostic criteria". J Med Genet 37 (11): 828–30. doi:10.1136/jmg.37.11.828. PMC 1734465. PMID 11073535. 
• Kelly P (2003). "Hereditary breast cancer considering Cowden syndrome: a case study". Cancer Nurs 26 (5): 370–5. doi:10.1097/00002820-200310000-00005. PMID 14710798. 
• Pilarski R, Eng C (2004). "Will the real Cowden syndrome please stand up (again)? Expanding mutational and clinical spectra of the PTEN hamartoma tumour syndrome". J Med Genet 41 (5): 323–6. doi:10.1136/jmg.2004.018036. PMC 1735782. PMID 15121767. 
• Waite KA, Eng C (2002). "Protean PTEN: Form and Function". Am J Hum Genet 70 (4): 829–44. doi:10.1086/340026. PMC 379112. PMID 11875759. 
• Zhou XP, Waite KA, Pilarski R, Hampel H, Fernandez MJ, Bos C, Dasouki M, Feldman GL, Greenberg LA, Ivanovich J, Matloff E, Patterson A, Pierpont ME, Russo D, Nassif NT, Eng C (2003). "Germline PTEN Promoter Mutations and Deletions in Cowden/Bannayan-Riley-Ruvalcaba Syndrome Result in Aberrant PTEN Protein and Dysregulation of the Phosphoinositol-3-Kinase/Akt Pathway". Am J Hum Genet 73 (2): 404–11. doi:10.1086/377109. PMC 1180378. PMID 12844284. 

External links

• GeneReviews/NCBI/NIH/UW entry on PTEN Hamartoma Tumor Syndrome (PHTS)
• Cancer.Net: Cowden Syndrome

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

• 1. カウデン症候群などのPTEN過誤腫症候群 pten hamartoma tumor syndrome including cowden syndrome
• 2. 表皮母斑および表皮母斑症候群 epidermal nevus and epidermal nevus syndrome
• 3. 子宮体癌：臨床的特徴および診断 endometrial carcinoma clinical features and diagnosis
• 4. BRCA1 and BRCA2: Prevalence and risks for breast and ovarian cancer
• 5. 小児における甲状腺結節および癌 thyroid nodules and cancer in children

English Journal

• Should patients with Cowden syndrome undergo prophylactic thyroidectomy?

• Milas M, Mester J, Metzger R, Shin J, Mitchell J, Berber E, Siperstein AE, Eng C.SourceDepartment of Surgery, Oregon Health and Sciences University, Portland, OR. Electronic address: milas@ohsu.edu.
• Surgery.Surgery.2012 Dec;152(6):1201-10. doi: 10.1016/j.surg.2012.08.055.
• BACKGROUND: Cowden syndrome (CS) is dominantly inherited and predisposes patients to tumors in multiple organs. We characterized CS-associated malignant and benign thyroid disease.METHODS: Of data from 3,477 prospectively recruited CS patients with known genetic analysis, we analyzed 225 PTEN mutati
• PMID 23158187

• ["Molecular apocrine" carcinoma and disease of Cowden].

• Longy M.SourceLaboratoire de génétique moléculaire, département de pathologie, CRLCC, institut Bergonié, 229, Cours de l'Argonne, 33076 Bordeaux, France. Electronic address: longy@bergonie.org.
• Annales de pathologie.Ann Pathol.2012 Nov;32(5 Suppl):S42-3. doi: 10.1016/j.annpat.2012.09.010. Epub 2012 Oct 11.
• PMID 23127936

Japanese Journal

• 便潜血を契機に診断され<I>PTEN</I>遺伝子変異を認めたCowden病の1例

• 日本臨床外科学会雑誌 75(5), 1180-1185, 2014
• NAID 130004706259

• 人間ドックの上部消化管内視鏡検査を契機にCowden病の診断に至った1例

• 人間ドック (Ningen Dock) 29(1), 47-51, 2014
• NAID 130004697498

• 胸腺腫瘍を合併したCowden病の1例

• 日本臨床外科学会雑誌 74(10), 2685-2689, 2013
• NAID 130004518515

Related Links

• Cowden Disease (Multiple Hamartoma Syndrome)

Cowden disease, also termed Cowden syndrome and multiple hamartoma syndrome, is an autosomal dominant condition with variable expression that results most commonly (80%) from a mutation in the PTEN gene on arm 10q, as reported by Liaw et al. [1] Originally described in 1963 by Lloyd and Dennis, Cowden disease ...

• Cowden Disease - definition of Cowden Disease in the ...

disease /dis·ease/ (dĭ-zēz´) any deviation from or interruption of the normal structure or function of any body part, organ, or system that is manifested by a characteristic set of symptoms and signs and whose etiology, pathology, and ...

Related Pictures

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★リンクテーブル★

リンク元	「カウデン症候群」「multiple hamartoma syndrome」
関連記事	「disease」

「カウデン症候群」

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英

Cowden syndrome, CS

同

Cowden症候群、カウデン病 コードン病 Cowden病 Cowden disease Cowden's disease、多発性過誤腫症候群 multiple hamartoma syndrome

関

[[]]

「multiple hamartoma syndrome」

　　[★] カウデン症候群

関

Cowden disease

「disease」

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• n.

疾患：illnessより厳密な概念。「ある臓器に明確な障害が確認され、それによって症状が出ているとはっきり説明できる場合」 (PSY.9)

特定の原因、病態生理、症状、経過、予後、病理組織所見が全てそろった場合 (PSY.9)

• something that is very wrong with people's attitudes, way of life or with society.

関

ail、ailment、disease entity、disorder、ill、illness、malady、sick、sickness

• 注意

disease ≠ illness ≠ disorder