Cowden syndrome: Difference between revisions

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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 mutations in the gene. These cases occur in people with no history of the disorder in their family.  It is characterized by numerous [[hamartoma]]s, among other symptoms.
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 mutations in the gene. These cases occur in people with no history of the disorder in their family.  It is characterized by numerous [[hamartoma]]s, among other symptoms.


==DIfferentiating Cowden syndrome from other diseases==
==Differentiating Cowden syndrome from other diseases==


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===Differentiating from other diseases causing multiple polyps===
{|
|- style="background: #4479BA; color: #FFFFFF; text-align: center;"
! rowspan="2" |Diseases
! colspan="3" |History and Symptoms
! colspan="3" |Physical Examination
! colspan="3" |Laboratory Findings
! rowspan="2" |Other Findings
|- style="background: #4479BA; color: #FFFFFF; text-align: center;"
!Abdominal Pain
!Rectal Bleeding
!Fatigue
!Abdominal Tenderness
!Hyperpigmentation
!Anemia
!Gene(s)
!Gastrointestinal Tumors
!Cancers
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |'''Familial Adenomatous Polyposis'''
| style="background: #F5F5F5; padding: 5px; text-align: center;" | +
| style="background: #F5F5F5; padding: 5px; text-align: center;" | +
| style="background: #F5F5F5; padding: 5px; text-align: center;" | +
| style="background: #F5F5F5; padding: 5px; text-align: center;" | +/–
| style="background: #F5F5F5; padding: 5px; text-align: center;" | –
| style="background: #F5F5F5; padding: 5px; text-align: center;" | +
| style="background: #F5F5F5; padding: 5px; text-align: left;" |
* [[APC (gene)|''APC'' gene]]
* [[MUTYH|''MUTYH'' gene]]
| style="background: #F5F5F5; padding: 5px; text-align: left;" |
* [[Adenoma]]+++
| style="background: #F5F5F5; padding: 5px; text-align: left;" |
* [[Colon (anatomy)|Colon]]
* [[Brain]]
* [[Thyroid]]
| style="background: #F5F5F5; padding: 5px; text-align: left;" |
* [[Desmoid tumor]]
* [[Osteoma]]
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Peutz-Jeghers syndrome|'''Peutz–Jeghers syndrome''']]
| style="background: #F5F5F5; padding: 5px; text-align: center;" | +
| style="background: #F5F5F5; padding: 5px; text-align: center;" | +
| style="background: #F5F5F5; padding: 5px; text-align: center;" | +
| style="background: #F5F5F5; padding: 5px; text-align: center;" | +
| style="background: #F5F5F5; padding: 5px; text-align: center;" | +
| style="background: #F5F5F5; padding: 5px; text-align: center;" | +
| style="background: #F5F5F5; padding: 5px; text-align: center;" |
* [[STK11]] (LBK1) gene
| style="background: #F5F5F5; padding: 5px; text-align: left;" |
* [[Adenoma]]+
* [[Hamartoma]]+++
| style="background: #F5F5F5; padding: 5px; text-align: left;" |
* Breast
* Lung
* Pancreas
* [[Ovaries]]
* Sertoli cells
* Uterine
| style="background: #F5F5F5; padding: 5px; text-align: left;" |
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |'''Juvenile Polyposis Syndrome'''
| style="background: #F5F5F5; padding: 5px; text-align: center;" | +
| style="background: #F5F5F5; padding: 5px; text-align: center;" |
| style="background: #F5F5F5; padding: 5px; text-align: center;" | +
| style="background: #F5F5F5; padding: 5px; text-align: center;" | –
| style="background: #F5F5F5; padding: 5px; text-align: center;" | –
| style="background: #F5F5F5; padding: 5px; text-align: center;" | –
| style="background: #F5F5F5; padding: 5px; text-align: left;" |
* SMAD4
* [[BMPR1A]]
| style="background: #F5F5F5; padding: 5px; text-align: left;" |
* [[Adenoma]]+ 
* [[Hamartoma]]+++
| style="background: #F5F5F5; padding: 5px; text-align: left;" |
* [[Colon (anatomy)|Colon]]
| style="background: #F5F5F5; padding: 5px; text-align: center;" |
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Cowden syndrome|'''Cowden Syndrome''']]
| style="background: #F5F5F5; padding: 5px; text-align: center;" | –
| style="background: #F5F5F5; padding: 5px; text-align: center;" | –
| style="background: #F5F5F5; padding: 5px; text-align: center;" | –
| style="background: #F5F5F5; padding: 5px; text-align: center;" | –
| style="background: #F5F5F5; padding: 5px; text-align: left;" |
* [[Axillary]]+ [[Inguinal region|Inguinal]]+ [[Facial]]+
| style="background: #F5F5F5; padding: 5px; text-align: center;" | –
| style="background: #F5F5F5; padding: 5px; text-align: left;" |
* [[PTEN (gene)|PTEN]]
| style="background: #F5F5F5; padding: 5px; text-align: left;" |
* [[Adenoma]]+ 
* [[Hamartoma]]+++
| style="background: #F5F5F5; padding: 5px; text-align: left;" |
* [[Breast]]
* [[Thyroid]]
* [[Endometrium]]
| style="background: #F5F5F5; padding: 5px; text-align: left;" |
* [[Trichilemmoma]]
* Skin hamartoma
* Hyperplastic polyp
* Macrocephaly
* Breast fibrosis
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Carney syndrome|'''Carney Syndrome''']]
| style="background: #F5F5F5; padding: 5px; text-align: center;" | –
| style="background: #F5F5F5; padding: 5px; text-align: center;" | –
| style="background: #F5F5F5; padding: 5px; text-align: center;" | –
| style="background: #F5F5F5; padding: 5px; text-align: center;" | –
| style="background: #F5F5F5; padding: 5px; text-align: left;" |
* [[Facial]]+ [[Mucous membrane|Mucosal]]+
| style="background: #F5F5F5; padding: 5px; text-align: center;" | –
| style="background: #F5F5F5; padding: 5px; text-align: left;" |
* [[PRKAR1A]]
| style="background: #F5F5F5; padding: 5px; text-align: center;" |
| style="background: #F5F5F5; padding: 5px; text-align: left;" |
* [[Thyroid]]
* [[Sertoli-Leydig cell tumor|Sertoli Cell]]
| style="background: #F5F5F5; padding: 5px; text-align: left;" |
* Myxoma of [[skin]]
* Myxoma of [[heart]]
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Hereditary nonpolyposis colorectal cancer|'''Hereditary Non–Polyposis Colon Cancer''']]
| style="background: #F5F5F5; padding: 5px; text-align: center;" | –
| style="background: #F5F5F5; padding: 5px; text-align: center;" | +
| style="background: #F5F5F5; padding: 5px; text-align: center;" | +
| style="background: #F5F5F5; padding: 5px; text-align: center;" | +/–
| style="background: #F5F5F5; padding: 5px; text-align: center;" | –
| style="background: #F5F5F5; padding: 5px; text-align: center;" | +
| style="background: #F5F5F5; padding: 5px; text-align: left;" |
* [[MLH1]]
* [[MSH2]]
* [[MSH3]]
* [[MSH6]]
* [[PMS1]]
* [[PMS2]]
| style="background: #F5F5F5; padding: 5px; text-align: left;" |
* [[Adenoma]]+
| style="background: #F5F5F5; padding: 5px; text-align: left;" |
* [[Endometrium]]
* [[Stomach]]
* [[Kidney|Kidneys]]
* [[Ureter]]
* [[Ovary|Ovaries]]
| style="background: #F5F5F5; padding: 5px; text-align: left;" |
* [[Sebaceous gland|Sebaceous]] [[adenoma]]
|}


==References==
==References==

Revision as of 23:26, 27 February 2018

Cowden syndrome
ICD-9 759.6
OMIM 158350
DiseasesDB 31336
MeSH D006223

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Cowden syndrome is an inherited disorder characterized by multiple tumor-like growths called hamartomas and an increased risk of certain forms of cancer. Almost everyone with this condition has hamartomas. These small, noncancerous growths 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. People with Cowden syndrome have an increased risk of developing several types of cancer, including cancers of the breast, thyroid, and uterus. Indeed, women with Cowden syndrome have as much as a 25-50% lifetime risk of developing breast cancer. (Robbins & Cotran (2004). Pathological Basis of Disease, 7th Edition. Elsevier. p. 1134.) Noncancerous breast and thyroid diseases are also common. Other signs and symptoms of Cowden syndrome can include an enlarged head, a rare noncancerous brain tumor called Lhermitte-Duclos disease and mental retardation.

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.

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.

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 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.

Differentiating Cowden syndrome from other diseases

Disease Gene Chromosome Differentiating Features Components of MEN Diagnosis
Parathyroid Pitutary Pancreas
von Hippel-Lindau syndrome Von Hippel–Lindau tumor suppressor 3p25.3
  • Angiomatosis, 
  • Hemangioblastomas,
  • Pheochromocytoma, 
  • Renal cell carcinoma,
  • Pancreatic cysts (pancreatic serous cystadenoma)
  • Endolymphatic sac tumor,
  • Bilateral papillary cystadenomas of the epididymis (men) or broad ligament of the uterus (women)
- - +
  • Clinical diagnosis
  • In hereditary VHL, disease techniques such as Southern blotting and gene sequencing can be used to analyse DNA and identify mutations.
Carney complex  PRKAR1A 17q23-q24
  • Myxomas of the heart
  • Hyperpigmentation of the skin (lentiginosis)
  • Endocrine (ACTH-independent Cushing's syndrome due to primary pigmented nodular adrenocortical disease)
- - -
  • Clinical diagnosis
Neurofibromatosis type 1 RAS 17 - - - Prenatal
  • Chorionic villus sampling or amniocentesis can be used to detect NF-1 in the fetus.

Postnatal Cardinal Clinical Features" are required for positive diagnosis.

  • Six or more café-au-lait spots over 5 mm in greatest diameter in pre-pubertal individuals and over 15 mm in greatest diameter in post-pubertal individuals.
  • Two or more neurofibromas of any type or 1 plexiform neurofibroma
  • Freckling in the axillary (Crowe sign) or inguinal regions
  • Optic glioma
  • Two or more Lisch nodules (pigmented iris hamartomas)
  • A distinctive osseous lesion such as sphenoid dysplasia, or thinning of the long bone cortex with or without pseudarthrosis.
Li-Fraumeni syndrome TP53 17 Early onset of diverse amount of cancers such as - - -

Criteria

  • Sarcoma at a young age (below 45)
  • A first-degree relative diagnosed with any cancer at a young age (below 45)
  • A first or second degree relative with any cancer diagnosed before age 60.
Gardner's syndrome APC  5q21
  • Multiple polyps in the colon 
  • Osteomas of the skull
  • Thyroid cancer,
  • Epidermoid cysts,
  • Fibromas
  • Desmoid tumors
- - -
  • Clinical diagnosis
  • Colonoscopy
Multiple endocrine neoplasia type 2 RET - + - -

Criteria Two or more specific endocrine tumors

Cowden syndrome PTEN -  Hamartomas - - -
  • PTEN mutation probability risk calculator
Acromegaly/gigantism - - - + -
Pituitary adenoma - - - + -
Hyperparathyroidism - - - + - -
  • An elevated concentration of serum calcium with elevated parathyroid hormone level is diagnostic of primary hyperparathyroidism.
  • Most consistent laboratory findings associated with the diagnosis of secondary hyperparathyroidism include elevated serum parathyroid hormone level and low to normal serum calcium.
  • An elevated concentration of serum calcium with elevated parathyroid hormone level in post renal transplant patients is diagnostic of tertiary hyperparathyoidism.
Pheochromocytoma/paraganglioma

VHL RET NF1   SDHB  SDHD

- Characterized by - - -
  • Increased catecholamines and metanephrines in plasma (blood) or through a 24-hour urine collection.
Adrenocortical carcinoma
  • p53
  • Retinoblastoma h19
  • Insulin-like growth factor II (IGF-II)
  • p57kip2
17p, 13q  - - -
  • Increased serum glucose
  • Increased urine cortisol
  • Serum androstenedione and dehydroepiandrosterone
  • Low serum potassium
  • Low plasma renin activity
  • High serum aldosterone.
  • Excess serum estrogen.
Adapted from Toledo SP, Lourenço DM, Toledo RA. A differential diagnosis of inherited endocrine tumors and their tumor counterparts, journal=Clinics (Sao Paulo), volume= 68, issue= 7, 07/24/2013[1]

Differentiating from other diseases causing multiple polyps

Diseases History and Symptoms Physical Examination Laboratory Findings Other Findings
Abdominal Pain Rectal Bleeding Fatigue Abdominal Tenderness Hyperpigmentation Anemia Gene(s) Gastrointestinal Tumors Cancers
Familial Adenomatous Polyposis + + + +/– +
Peutz–Jeghers syndrome + + + + + +
  • Breast
  • Lung
  • Pancreas
  • Ovaries
  • Sertoli cells
  • Uterine
Juvenile Polyposis Syndrome + +
Cowden Syndrome
  • Trichilemmoma
  • Skin hamartoma
  • Hyperplastic polyp
  • Macrocephaly
  • Breast fibrosis
Carney Syndrome
Hereditary Non–Polyposis Colon Cancer + + +/– +

References

  1. Toledo SP, Lourenço DM, Toledo RA (2013). "A differential diagnosis of inherited endocrine tumors and their tumor counterparts". Clinics (Sao Paulo). 68 (7): 1039–56. doi:10.6061/clinics/2013(07)24. PMC 3715026. PMID 23917672.
  • 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. PMID 11950848.
  • Eng C (2000). "Will the real Cowden syndrome please stand up: revised diagnostic criteria". J Med Genet. 37 (11): 828–30. PMID 11073535.
  • Kelly P (2003). "Hereditary breast cancer considering Cowden syndrome: a case study". Cancer Nurs. 26 (5): 370–5. 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. PMID 15121767.
  • Waite KA, Eng C (2002). "Protean PTEN: form and function". Am J Hum Genet. 70 (4): 829–44. 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. PMID 12844284.

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