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PTEN hamartoma tumor syndrome(PHTS)

MedGen UID:
368366
Concept ID:
C1959582
Neoplastic Process
Synonyms: PHTS; PTEN Hamartomatous Tumour Syndrome
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Sources: HPO, OMIM, Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
Autosomal dominant inheritance (HPO, OMIM, Orphanet)
SNOMED CT: PTEN hamartoma tumor syndrome (722859001)
 
Gene (location): PTEN (10q23.31)
Related gene: AKT1
OMIM®: 601728
Orphanet: ORPHA306498

Definition

The PTEN hamartoma tumor syndrome (PHTS) includes Cowden syndrome (CS), Bannayan-Riley-Ruvalcaba syndrome (BRRS), PTEN-related Proteus syndrome (PS), and Proteus-like syndrome. CS is a multiple hamartoma syndrome with a high risk for benign and malignant tumors of the thyroid, breast, and endometrium. Affected individuals usually have macrocephaly, trichilemmomas, and papillomatous papules, and present by the late 20s. The lifetime risk of developing breast cancer is 85%, with an average age of diagnosis between 38 and 46 years. The lifetime risk for thyroid cancer (usually follicular, rarely papillary, but never medullary thyroid cancer) is approximately 35%. The risk for endometrial cancer may approach 28%. BRRS is a congenital disorder characterized by macrocephaly, intestinal hamartomatous polyposis, lipomas, and pigmented macules of the glans penis. PS is a complex, highly variable disorder involving congenital malformations and hamartomatous overgrowth of multiple tissues, as well as connective tissue nevi, epidermal nevi, and hyperostoses. Proteus-like syndrome is undefined but refers to individuals with significant clinical features of PS who do not meet the diagnostic criteria for PS. [from GTR]

Additional description

From GeneReviews
The PTEN hamartoma tumor syndrome (PHTS) includes Cowden syndrome (CS), Bannayan-Riley-Ruvalcaba syndrome (BRRS), PTEN-related Proteus syndrome (PS), and Proteus-like syndrome. CS is a multiple hamartoma syndrome with a high risk for benign and malignant tumors of the thyroid, breast, and endometrium. Affected individuals usually have macrocephaly, trichilemmomas, and papillomatous papules, and present by the late 20s. The lifetime risk of developing breast cancer is 85%, with an average age of diagnosis between 38 and 46 years. The lifetime risk for thyroid cancer (usually follicular, rarely papillary, but never medullary thyroid cancer) is approximately 35%. The risk for endometrial cancer may approach 28%. BRRS is a congenital disorder characterized by macrocephaly, intestinal hamartomatous polyposis, lipomas, and pigmented macules of the glans penis. PS is a complex, highly variable disorder involving congenital malformations and hamartomatous overgrowth of multiple tissues, as well as connective tissue nevi, epidermal nevi, and hyperostoses. Proteus-like syndrome is undefined but refers to individuals with significant clinical features of PS who do not meet the diagnostic criteria for PS.  https://www.ncbi.nlm.nih.gov/books/NBK1488

Professional guidelines

PubMed

Syngal S, Brand RE, Church JM, Giardiello FM, Hampel HL, Burt RW; American College of Gastroenterology.
Am J Gastroenterol 2015 Feb;110(2):223-62; quiz 263. Epub 2015 Feb 3 doi: 10.1038/ajg.2014.435. PMID: 25645574Free PMC Article
ACMG Board of Directors.
Genet Med 2015 Jan;17(1):68-9. Epub 2014 Nov 13 doi: 10.1038/gim.2014.151. PMID: 25356965
Daly MB, Pilarski R, Axilbund JE, Buys SS, Crawford B, Friedman S, Garber JE, Horton C, Kaklamani V, Klein C, Kohlmann W, Kurian A, Litton J, Madlensky L, Marcom PK, Merajver SD, Offit K, Pal T, Pasche B, Reiser G, Shannon KM, Swisher E, Voian NC, Weitzel JN, Whelan A, Wiesner GL, Dwyer MA, Kumar R; National comprehensive cancer network.
J Natl Compr Canc Netw 2014 Sep;12(9):1326-38. PMID: 25190698
Green RC, Berg JS, Grody WW, Kalia SS, Korf BR, Martin CL, McGuire AL, Nussbaum RL, O'Daniel JM, Ormond KE, Rehm HL, Watson MS, Williams MS, Biesecker LG; American College of Medical Genetics and Genomics.
Genet Med 2013 Jul;15(7):565-74. Epub 2013 Jun 20 doi: 10.1038/gim.2013.73. PMID: 23788249Free PMC Article
Schaefer GB, Mendelsohn NJ; Professional Practice and Guidelines Committee.
Genet Med 2013 May;15(5):399-407. Epub 2013 Mar 21 doi: 10.1038/gim.2013.32. PMID: 23519317
Saslow D, Boetes C, Burke W, Harms S, Leach MO, Lehman CD, Morris E, Pisano E, Schnall M, Sener S, Smith RA, Warner E, Yaffe M, Andrews KS, Russell CA; American Cancer Society Breast Cancer Advisory Group.
CA Cancer J Clin 2007 Mar-Apr;57(2):75-89. PMID: 17392385

External

Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics.

Recent clinical studies

Etiology

Saletti V, Esposito S, Maccaro A, Giglio S, Valentini LG, Chiapparini L
Eur J Med Genet 2017 May;60(5):261-264. Epub 2017 Mar 7 doi: 10.1016/j.ejmg.2017.03.002. PMID: 28286253
Ngeow J, Eng C
Methods Mol Biol 2016;1388:63-73. doi: 10.1007/978-1-4939-3299-3_6. PMID: 27033071
Mester J, Charis E
Handb Clin Neurol 2015;132:129-37. doi: 10.1016/B978-0-444-62702-5.00009-3. PMID: 26564076
Ngeow J, Eng C
Methods 2015 May;77-78:11-9. Epub 2014 Oct 22 doi: 10.1016/j.ymeth.2014.10.011. PMID: 25461771
Stanich PP, Pilarski R, Rock J, Frankel WL, El-Dika S, Meyer MM
World J Gastroenterol 2014 Feb 21;20(7):1833-8. doi: 10.3748/wjg.v20.i7.1833. PMID: 24587660Free PMC Article

Diagnosis

Ngeow J, Eng C
Methods Mol Biol 2016;1388:63-73. doi: 10.1007/978-1-4939-3299-3_6. PMID: 27033071
Nosé V
Head Neck Pathol 2016 Jun;10(2):131-8. Epub 2016 Mar 14 doi: 10.1007/s12105-016-0708-7. PMID: 26975628Free PMC Article
Mester J, Charis E
Handb Clin Neurol 2015;132:129-37. doi: 10.1016/B978-0-444-62702-5.00009-3. PMID: 26564076
Cameselle-Teijeiro J, Fachal C, Cabezas-Agrícola JM, Alfonsín-Barreiro N, Abdulkader I, Vega-Gliemmo A, Hermo JA
Am J Clin Pathol 2015 Aug;144(2):322-8. doi: 10.1309/AJCP84INGJUVTBME. PMID: 26185318
Ngeow J, Eng C
Methods 2015 May;77-78:11-9. Epub 2014 Oct 22 doi: 10.1016/j.ymeth.2014.10.011. PMID: 25461771

Therapy

Leipert J, Kässner F, Schuster S, Händel N, Körner A, Kiess W, Garten A
Nutr Cancer 2016;68(2):342-9. Epub 2016 Mar 4 doi: 10.1080/01635581.2016.1145244. PMID: 26943752
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Nat Clin Pract Oncol 2008 Jun;5(6):357-61. Epub 2008 Apr 22 doi: 10.1038/ncponc1112. PMID: 18431376

Prognosis

Stanich PP, Pilarski R, Rock J, Frankel WL, El-Dika S, Meyer MM
World J Gastroenterol 2014 Feb 21;20(7):1833-8. doi: 10.3748/wjg.v20.i7.1833. PMID: 24587660Free PMC Article
Hopman SM, Van Rijn RR, Eng C, Bras J, Alders M, van der Horst CM, Hennekam RC, Merks JH
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Breast Cancer Res Treat 2010 Nov;124(2):459-65. Epub 2010 Mar 27 doi: 10.1007/s10549-010-0839-6. PMID: 20349131
Jenny B, Radovanovic I, Haenggeli CA, Delavelle J, Rüfenacht D, Kaelin A, Blouin JL, Bottani A, Rilliet B
J Neurosurg 2007 Oct;107(4 Suppl):307-13. doi: 10.3171/PED-07/10/307. PMID: 17941496
Schaffer JV, Kamino H, Witkiewicz A, McNiff JM, Orlow SJ
Arch Dermatol 2006 May;142(5):625-32. doi: 10.1001/archderm.142.5.625. PMID: 16702501

Clinical prediction guides

Nathan N, Keppler-Noreuil KM, Biesecker LG, Moss J, Darling TN
Dermatol Clin 2017 Jan;35(1):51-60. doi: 10.1016/j.det.2016.07.001. PMID: 27890237Free PMC Article
Galatola M, Miele E, Strisciuglio C, Paparo L, Rega D, Delrio P, Duraturo F, Martinelli M, Rossi GB, Staiano A, Izzo P, De Rosa M
World J Gastroenterol 2013 Dec 14;19(46):8659-70. doi: 10.3748/wjg.v19.i46.8659. PMID: 24379584Free PMC Article
Venturini G, Moulin AP, Deprez M, Uffer S, Bottani A, Zografos L, Rivolta C
Ophthalmology 2012 Apr;119(4):857-64. Epub 2012 Jan 26 doi: 10.1016/j.ophtha.2011.09.057. PMID: 22281088
Shiovitz S, Everett J, Huang SC, Orloff MS, Eng C, Gruber SB
Breast Cancer Res Treat 2010 Nov;124(2):459-65. Epub 2010 Mar 27 doi: 10.1007/s10549-010-0839-6. PMID: 20349131
Schaffer JV, Kamino H, Witkiewicz A, McNiff JM, Orlow SJ
Arch Dermatol 2006 May;142(5):625-32. doi: 10.1001/archderm.142.5.625. PMID: 16702501

Recent systematic reviews

Daly MB, Pilarski R, Axilbund JE, Buys SS, Crawford B, Friedman S, Garber JE, Horton C, Kaklamani V, Klein C, Kohlmann W, Kurian A, Litton J, Madlensky L, Marcom PK, Merajver SD, Offit K, Pal T, Pasche B, Reiser G, Shannon KM, Swisher E, Voian NC, Weitzel JN, Whelan A, Wiesner GL, Dwyer MA, Kumar R; National comprehensive cancer network.
J Natl Compr Canc Netw 2014 Sep;12(9):1326-38. PMID: 25190698
Stanich PP, Pilarski R, Rock J, Frankel WL, El-Dika S, Meyer MM
World J Gastroenterol 2014 Feb 21;20(7):1833-8. doi: 10.3748/wjg.v20.i7.1833. PMID: 24587660Free PMC Article
Pilarski R, Burt R, Kohlman W, Pho L, Shannon KM, Swisher E
J Natl Cancer Inst 2013 Nov 6;105(21):1607-16. Epub 2013 Oct 17 doi: 10.1093/jnci/djt277. PMID: 24136893

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