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Peutz-Jeghers syndrome(PJS)

MedGen UID:
18404
Concept ID:
C0031269
Disease or Syndrome
Synonyms: Lentiginosis, perioral; Periorificial lentiginosis syndrome; Peutz-Jeghers polyposis; PJS; Polyposis, hamartomatous intestinal; Polyps-and-spots syndrome
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Autosomal dominant inheritance refers to genetic conditions that occur when a mutation is present in one copy of a given gene (i.e., the person is heterozygous).
SNOMED CT: Perioral lentiginosis (54411001); PJS - Peutz-Jehgers syndrome (54411001); Peutz-Jeghers polyposis (54411001); Peutz-Jeghers syndrome (54411001); Periorificial lentiginosis syndrome (54411001)
 
Gene: STK11
Cytogenetic location: 19p13.3
OMIM®: 175200
Orphanet: ORPHA2869

Disease characteristics

Excerpted from the GeneReview: Peutz-Jeghers Syndrome
Peutz-Jeghers syndrome (PJS) is an autosomal-dominant condition characterized by the association of gastrointestinal polyposis, mucocutaneous pigmentation, and cancer predisposition. Peutz-Jeghers-type hamartomatous polyps are most common in the small intestine (in order of prevalence: in the jejunum, ileum, and duodenum) but can also occur in the stomach, large bowel, and extraintestinal sites including the renal pelvis, bronchus, gall bladder, nasal passages, urinary bladder, and ureters. Gastrointestinal polyps can result in chronic bleeding and anemia and also cause recurrent obstruction and intussusception requiring repeated laparotomy and bowel resection. Mucocutaneous hyperpigmentation presents in childhood as dark blue to dark brown macules around the mouth, eyes, and nostrils, in the perianal area, and on the buccal mucosa. Hyperpigmented macules on the fingers are common. The macules may fade in puberty and adulthood. Individuals with Peutz-Jeghers syndrome are at increased risk for a wide variety of epithelial malignancies (colorectal, gastric, pancreatic, breast, and ovarian cancers). Females are at risk for sex cord tumors with annular tubules (SCTAT), a benign neoplasm of the ovaries, and adenoma malignum of the cervix, a rare aggressive cancer. Males occasionally develop large calcifying Sertoli cell tumors (LCST) of the testes, which secrete estrogen and can lead to gynecomastia, advanced skeletal age, and ultimately short stature, if untreated. [from GeneReviews]
Full text of GeneReview (by section):
Summary  |  Diagnosis  |  Clinical Characteristics  |  Differential Diagnosis  |  Management  |  Genetic Counseling  |  Resources  |  Molecular Genetics  |  References  |  Chapter Notes
Authors:
Thomas J McGarrity  |  Christopher I Amos  |  Marsha L Frazier, et. al.   view full author information

Additional descriptions

From OMIM
Peutz-Jeghers syndrome is an autosomal dominant disorder characterized by melanocytic macules of the lips, buccal mucosa, and digits; multiple gastrointestinal hamartomatous polyps; and an increased risk of various neoplasms.  http://www.omim.org/entry/175200
From GHR
Peutz-Jeghers syndrome is characterized by the development of noncancerous growths called hamartomatous polyps in the gastrointestinal tract (particularly the stomach and intestines) and a greatly increased risk of developing certain types of cancer. Children with Peutz-Jeghers syndrome often develop small, dark-colored spots on the lips, around and inside the mouth, near the eyes and nostrils, and around the anus. These spots may also occur on the hands and feet. They appear during childhood and often fade as the person gets older. In addition, most people with Peutz-Jeghers syndrome develop multiple polyps in the stomach and intestines during childhood or adolescence. Polyps can cause health problems such as recurrent bowel obstructions, chronic bleeding, and abdominal pain. People with Peutz-Jeghers syndrome have a high risk of developing cancer during their lifetimes. Cancers of the gastrointestinal tract, pancreas, cervix, ovary, and breast are among the most commonly reported tumors.  http://ghr.nlm.nih.gov/condition/peutz-jeghers-syndrome

Clinical features

Intestinal polyposis
MedGen UID:
152871
Concept ID:
C0744333
Finding
A polypoid tumor that arises from any part of the gastrointestinal tract and protrudes into the lumen. Representative examples include adenomatous polyps, hyperplastic polyps, and hamartomatous polyps.
Precocious puberty with Sertoli cell tumor
MedGen UID:
357406
Concept ID:
C1868007
Finding
Gastrointestinal carcinoma
MedGen UID:
505328
Concept ID:
CN002428
Finding
Neoplasm of the pancreas
MedGen UID:
425115
Concept ID:
CN002617
Finding
A tumor (abnormal growth of tissue) of the pancreas.
Breast carcinoma
MedGen UID:
428324
Concept ID:
CN002714
Finding
The presence of a carcinoma of the breast.
Hamartomatous polyposis
MedGen UID:
505621
Concept ID:
CN003889
Finding
Polyp-like protrusions which are histologically hamartomas. These can occur throughout the gastrointestinal tract. Hamartomatous polyps are composed of the normal cellular elements of the gastrointestinal tract, but have a markedly distorted architecture.
Neoplasm of the stomach
MedGen UID:
425846
Concept ID:
CN005879
Finding
A tumor (abnormal growth of tissue) of the stomach.
Renal neoplasm
MedGen UID:
506302
Concept ID:
CN008586
Finding
The presence of a neoplasm of the kidney.
Uterine neoplasm
MedGen UID:
426773
Concept ID:
CN009610
Finding
A tumor (abnormal growth of tissue) of the uterus.
Testicular neoplasm
MedGen UID:
429628
Concept ID:
CN009614
Finding
The presence of a neoplasm of the testis.
Neoplasm of the breast
MedGen UID:
506444
Concept ID:
CN116912
Finding
A tumor (abnormal growth of tissue) of the breast.
Neoplasm of the colon
MedGen UID:
451644
Concept ID:
CN117169
Finding
Neoplasm of the lung
MedGen UID:
506475
Concept ID:
CN117419
Finding
Tumor of the lung.
Biliary tract neoplasm
MedGen UID:
506486
Concept ID:
CN117467
Finding
A tumor (abnormal growth of tissue) of the biliary system.
Ovarian neoplasm
MedGen UID:
506498
Concept ID:
CN117507
Finding
A tumor (abnormal growth of tissue) of the ovary.
Neoplasm of the rectum
MedGen UID:
451989
Concept ID:
CN117633
Finding
Esophageal neoplasm
MedGen UID:
451997
Concept ID:
CN117641
Finding
A tumor (abnormal growth of tissue) of the esophagus.
Neoplasm of the small intestine
MedGen UID:
452045
Concept ID:
CN117722
Finding
The presence of a neoplasm of the small intestine.
Abnormality of the ureter
MedGen UID:
374455
Concept ID:
C1840382
Finding
Precocious puberty with Sertoli cell tumor
MedGen UID:
357406
Concept ID:
C1868007
Finding
Ovarian cyst
MedGen UID:
504360
Concept ID:
CN000134
Finding
The presence of one or more cysts of the ovary.
Renal neoplasm
MedGen UID:
506302
Concept ID:
CN008586
Finding
The presence of a neoplasm of the kidney.
Uterine neoplasm
MedGen UID:
426773
Concept ID:
CN009610
Finding
A tumor (abnormal growth of tissue) of the uterus.
Testicular neoplasm
MedGen UID:
429628
Concept ID:
CN009614
Finding
The presence of a neoplasm of the testis.
Ovarian neoplasm
MedGen UID:
506498
Concept ID:
CN117507
Finding
A tumor (abnormal growth of tissue) of the ovary.
Abnormality of the mouth
MedGen UID:
424981
Concept ID:
CN000149
Finding
An abnormality of the mouth.
Nasal polyposis
MedGen UID:
506489
Concept ID:
CN117475
Finding
Polypoidal masses arising mainly from the mucous membranes of the nose and paranasal sinuses. They are freely movable and nontender overgrowths of the mucosa that frequently accompany allergic rhinitis.
Abnormal pigmentation of the oral mucosa
MedGen UID:
451944
Concept ID:
CN117561
Finding
An abnormality of the pigmentation of the mucosa of the mouth.
Lip hyperpigmentation
MedGen UID:
452036
Concept ID:
CN117706
Finding
Gynecomastia
MedGen UID:
409558
Concept ID:
C1963120
Finding
Breast carcinoma
MedGen UID:
428324
Concept ID:
CN002714
Finding
The presence of a carcinoma of the breast.
Neoplasm of the breast
MedGen UID:
506444
Concept ID:
CN116912
Finding
A tumor (abnormal growth of tissue) of the breast.
Precocious puberty with Sertoli cell tumor
MedGen UID:
357406
Concept ID:
C1868007
Finding
Clubbing of fingers
MedGen UID:
451999
Concept ID:
CN117649
Finding
Terminal broadening of the fingers (distal phalanges of the fingers).
Intestinal polyposis
MedGen UID:
152871
Concept ID:
C0744333
Finding
A polypoid tumor that arises from any part of the gastrointestinal tract and protrudes into the lumen. Representative examples include adenomatous polyps, hyperplastic polyps, and hamartomatous polyps.
Gastrointestinal infarctions
MedGen UID:
463581
Concept ID:
C3152231
Finding
Biliary tract abnormality
MedGen UID:
504714
Concept ID:
CN001013
Finding
An abnormality of the biliary tree.
Nausea and vomiting
MedGen UID:
505054
Concept ID:
CN001825
Finding
Abdominal pain
MedGen UID:
505060
Concept ID:
CN001834
Finding
An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) and perceived to originate in the abdomen.
Rectal prolapse
MedGen UID:
505063
Concept ID:
CN001840
Finding
Protrusion of the rectal mucous membrane through the anus.
Gastrointestinal hemorrhage
MedGen UID:
505164
Concept ID:
CN002030
Finding
Hemorrhage affecting the gastrointestinal tract.
Intussusception
MedGen UID:
505276
Concept ID:
CN002338
Finding
An abnormality of the intestine in which part of the intestine invaginates (telescopes) into another part of the intestine.
Intestinal bleeding
MedGen UID:
505281
Concept ID:
CN002346
Finding
Bleeding from the intestines.
Gastrointestinal carcinoma
MedGen UID:
505328
Concept ID:
CN002428
Finding
Neoplasm of the pancreas
MedGen UID:
425115
Concept ID:
CN002617
Finding
A tumor (abnormal growth of tissue) of the pancreas.
Hamartomatous polyposis
MedGen UID:
505621
Concept ID:
CN003889
Finding
Polyp-like protrusions which are histologically hamartomas. These can occur throughout the gastrointestinal tract. Hamartomatous polyps are composed of the normal cellular elements of the gastrointestinal tract, but have a markedly distorted architecture.
Intestinal obstruction
MedGen UID:
505771
Concept ID:
CN004620
Finding
Blockage or impairment of the normal flow of the contents of the intestine towards the anal canal.
Neoplasm of the stomach
MedGen UID:
425846
Concept ID:
CN005879
Finding
A tumor (abnormal growth of tissue) of the stomach.
Neoplasm of the colon
MedGen UID:
451644
Concept ID:
CN117169
Finding
Biliary tract neoplasm
MedGen UID:
506486
Concept ID:
CN117467
Finding
A tumor (abnormal growth of tissue) of the biliary system.
Neoplasm of the rectum
MedGen UID:
451989
Concept ID:
CN117633
Finding
Esophageal neoplasm
MedGen UID:
451997
Concept ID:
CN117641
Finding
A tumor (abnormal growth of tissue) of the esophagus.
Neoplasm of the small intestine
MedGen UID:
452045
Concept ID:
CN117722
Finding
The presence of a neoplasm of the small intestine.
Melanocytic nevus
MedGen UID:
504679
Concept ID:
CN000931
Finding
A oval and round, colored (usually medium-to dark brown, reddish brown, or flesh colored) lesion. Typically, a melanocytic nevus is less than 6 mm in diameter, but may be much smaller or larger.
Hypermelanotic macule
MedGen UID:
500898
Concept ID:
CN000969
Finding
A hyperpigmented circumscribed area of change in normal skin color without elevation or depression of any size.
Abnormality of nail color
MedGen UID:
451931
Concept ID:
CN117535
Finding
An anomaly of the color of the nail.
Lip hyperpigmentation
MedGen UID:
452036
Concept ID:
CN117706
Finding
Gastrointestinal hemorrhage
MedGen UID:
505164
Concept ID:
CN002030
Finding
Hemorrhage affecting the gastrointestinal tract.
Intestinal bleeding
MedGen UID:
505281
Concept ID:
CN002346
Finding
Bleeding from the intestines.
Iron deficiency anemia
MedGen UID:
504991
Concept ID:
CN001710
Finding
Gastrointestinal hemorrhage
MedGen UID:
505164
Concept ID:
CN002030
Finding
Hemorrhage affecting the gastrointestinal tract.
Intestinal bleeding
MedGen UID:
505281
Concept ID:
CN002346
Finding
Bleeding from the intestines.
Neoplasm of the lung
MedGen UID:
506475
Concept ID:
CN117419
Finding
Tumor of the lung.
Clubbing of fingers
MedGen UID:
451999
Concept ID:
CN117649
Finding
Terminal broadening of the fingers (distal phalanges of the fingers).

Professional guidelines

PubMed

Hampel H, Bennett RL, Buchanan A, Pearlman R, Wiesner GL; Guideline Development Group, American College of Medical Genetics and Genomics Professional Practice and Guidelines Committee and National Society of Genetic Counselors Practice Guidelines Committee
Genet Med 2015 Jan;17(1):70-87. Epub 2014 Nov 13 doi: 10.1038/gim.2014.147. [Epub ahead of print] PMID: 25394175
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. [Epub ahead of print] PMID: 23788249Free PMC Article
Canto MI, Harinck F, Hruban RH, Offerhaus GJ, Poley JW, Kamel I, Nio Y, Schulick RS, Bassi C, Kluijt I, Levy MJ, Chak A, Fockens P, Goggins M, Bruno M; International Cancer of Pancreas Screening (CAPS) Consortium
Gut 2013 Mar;62(3):339-47. Epub 2012 Nov 7 doi: 10.1136/gutjnl-2012-303108. [Epub ahead of print] PMID: 23135763Free PMC Article
Trepanier A, Ahrens M, McKinnon W, Peters J, Stopfer J, Grumet SC, Manley S, Culver JO, Acton R, Larsen-Haidle J, Correia LA, Bennett R, Pettersen B, Ferlita TD, Costalas JW, Hunt K, Donlon S, Skrzynia C, Farrell C, Callif-Daley F, Vockley CW; National Society of Genetic Counselors
J Genet Couns 2004 Apr;13(2):83-114. doi: 10.1023/B:JOGC.0000018821.48330.77. PMID: 15604628

Recent clinical studies

Etiology

Wang Z, Wu B, Mosig RA, Chen Y, Ye F, Zhang Y, Gong W, Gong L, Huang F, Wang X, Nie B, Zheng H, Cui M, Wang Y, Wang J, Chen C, Polydorides AD, Zhang DY, Martignetti JA, Jiang B
Hum Mutat 2014 Jul;35(7):851-8. Epub 2014 Jun 3 doi: 10.1002/humu.22549. [Epub ahead of print] PMID: 24652667
Dai L, Fu L, Liu D, Zhang K, Wu Y, Meng H, Zhang B, Guan X, Guo H, Bai Y
Dig Dis Sci 2014 Aug;59(8):1856-61. Epub 2014 Mar 7 doi: 10.1007/s10620-014-3077-7. [Epub ahead of print] PMID: 24604241
Urquhart P, Grimpen F, Lim GJ, Pizzey C, Stella DL, Tesar PA, Macrae FA, Appleyard MA, Brown GJ
Fam Cancer 2014 Jun;13(2):249-55. doi: 10.1007/s10689-014-9700-0. PMID: 24509884
Kobayashi Y, Masuda K, Kimura T, Nomura H, Hirasawa A, Banno K, Susumu N, Sugano K, Aoki D
Future Oncol 2014 Feb;10(2):171-7. doi: 10.2217/fon.13.180. PMID: 24490603
Vageli DP, Doukas SG, Markou A
Pediatr Blood Cancer 2013 Oct;60(10):E116-7. Epub 2013 May 15 doi: 10.1002/pbc.24579. [Epub ahead of print] PMID: 23677888

Diagnosis

Maslyankov S, Trifonov G, Kyoseva D, Fidoshev I, Tzoneva D, Velev G, Dimova I, Sokolov M, Koleva Q, Todorov G
Khirurgiia (Sofiia) 2014;(1):43-8. PMID: 25199243
Szanto P, Barbieru V, Badea R, Pop T, Rusu I, Al Hajjar N
J Gastrointestin Liver Dis 2014 Mar;23(1):91-4. PMID: 24689103
Wang Z, Wu B, Mosig RA, Chen Y, Ye F, Zhang Y, Gong W, Gong L, Huang F, Wang X, Nie B, Zheng H, Cui M, Wang Y, Wang J, Chen C, Polydorides AD, Zhang DY, Martignetti JA, Jiang B
Hum Mutat 2014 Jul;35(7):851-8. Epub 2014 Jun 3 doi: 10.1002/humu.22549. [Epub ahead of print] PMID: 24652667
Kobayashi Y, Masuda K, Kimura T, Nomura H, Hirasawa A, Banno K, Susumu N, Sugano K, Aoki D
Future Oncol 2014 Feb;10(2):171-7. doi: 10.2217/fon.13.180. PMID: 24490603
Tutar O, Kocak B, Velidedeoglu M, Baca B, Dikici S, Nurili F, Kantarci F
Scott Med J 2014 Feb;59(1):e9-13. Epub 2014 Jan 21 doi: 10.1177/0036933013519028. [Epub ahead of print] PMID: 24448402

Therapy

Ferraro GA, Romano T, De Francesco F, Grandone A, D'Andrea F, del Giudice EM, Cataldo C, Gatta G, Di Grezia G, Perrone L, Nicoletti G
Aesthetic Plast Surg 2013 Oct;37(5):1012-22. Epub 2013 Jul 17 doi: 10.1007/s00266-013-0188-z. [Epub ahead of print] PMID: 23860822
Resta N, Pierannunzio D, Lenato GM, Stella A, Capocaccia R, Bagnulo R, Lastella P, Susca FC, Bozzao C, Loconte DC, Sabbà C, Urso E, Sala P, Fornasarig M, Grammatico P, Piepoli A, Host C, Turchetti D, Viel A, Memo L, Giunti L, Stigliano V, Varesco L, Bertario L, Genuardi M, Lucci Cordisco E, Tibiletti MG, Di Gregorio C, Andriulli A, Ponz de Leon M; AIFEG
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Photodermatol Photoimmunol Photomed 2012 Aug;28(4):196-9. doi: 10.1111/j.1600-0781.2012.00672.x. PMID: 23017172
Langeveld D, Jansen M, de Boer DV, van Sprundel M, Brosens LA, Morsink FH, Giardiello FM, Offerhaus GJ, de Leng WW
Gut 2012 Jun;61(6):839-46. Epub 2011 Sep 22 doi: 10.1136/gutjnl-2011-300622. [Epub ahead of print] PMID: 21940722Free PMC Article
Triggiani V, Guastamacchia E, Renzulli G, Giagulli VA, Tafaro E, Licchelli B, Resta F, Sabbà C, Bagnulo R, Lastella P, Stella A, Resta N
Thyroid 2011 Nov;21(11):1273-7. Epub 2011 Aug 30 doi: 10.1089/thy.2011.0063. [Epub ahead of print] PMID: 21877933

Prognosis

Dai L, Fu L, Liu D, Zhang K, Wu Y, Meng H, Zhang B, Guan X, Guo H, Bai Y
Dig Dis Sci 2014 Aug;59(8):1856-61. Epub 2014 Mar 7 doi: 10.1007/s10620-014-3077-7. [Epub ahead of print] PMID: 24604241
Urquhart P, Grimpen F, Lim GJ, Pizzey C, Stella DL, Tesar PA, Macrae FA, Appleyard MA, Brown GJ
Fam Cancer 2014 Jun;13(2):249-55. doi: 10.1007/s10689-014-9700-0. PMID: 24509884
Tutar O, Kocak B, Velidedeoglu M, Baca B, Dikici S, Nurili F, Kantarci F
Scott Med J 2014 Feb;59(1):e9-13. Epub 2014 Jan 21 doi: 10.1177/0036933013519028. [Epub ahead of print] PMID: 24448402
Zaba O, Holbe D, Aretz S, Grohé C
Lung Cancer 2013 Nov;82(2):368-9. Epub 2013 Sep 2 doi: 10.1016/j.lungcan.2013.08.019. [Epub ahead of print] PMID: 24054548
Tse JY, Wu S, Shinagare SA, Lauwers GY, Yilmaz O, Wu CL, Deshpande V
Mod Pathol 2013 Sep;26(9):1235-40. Epub 2013 Apr 19 doi: 10.1038/modpathol.2013.44. [Epub ahead of print] PMID: 23599156

Clinical prediction guides

Dai L, Fu L, Liu D, Zhang K, Wu Y, Meng H, Zhang B, Guan X, Guo H, Bai Y
Dig Dis Sci 2014 Aug;59(8):1856-61. Epub 2014 Mar 7 doi: 10.1007/s10620-014-3077-7. [Epub ahead of print] PMID: 24604241
Urquhart P, Grimpen F, Lim GJ, Pizzey C, Stella DL, Tesar PA, Macrae FA, Appleyard MA, Brown GJ
Fam Cancer 2014 Jun;13(2):249-55. doi: 10.1007/s10689-014-9700-0. PMID: 24509884
Tutar O, Kocak B, Velidedeoglu M, Baca B, Dikici S, Nurili F, Kantarci F
Scott Med J 2014 Feb;59(1):e9-13. Epub 2014 Jan 21 doi: 10.1177/0036933013519028. [Epub ahead of print] PMID: 24448402
Ham S, Meachem SJ, Choong CS, Charles AK, Baynam GS, Jones TW, Samarajeewa NU, Simpson ER, Brown KA
J Clin Endocrinol Metab 2013 Dec;98(12):E1979-87. Epub 2013 Sep 13 doi: 10.1210/jc.2013-2291. [Epub ahead of print] PMID: 24037887
Tse JY, Wu S, Shinagare SA, Lauwers GY, Yilmaz O, Wu CL, Deshpande V
Mod Pathol 2013 Sep;26(9):1235-40. Epub 2013 Apr 19 doi: 10.1038/modpathol.2013.44. [Epub ahead of print] PMID: 23599156

Recent systematic reviews

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. [Epub ahead of print] PMID: 25645574
Chen XD, Yu YY, Yang L, Rui YY, Zhou ZG
Eur J Gastroenterol Hepatol 2012 Jun;24(6):722-6. doi: 10.1097/MEG.0b013e328351c1df. PMID: 22356785
Beggs AD, Latchford AR, Vasen HF, Moslein G, Alonso A, Aretz S, Bertario L, Blanco I, Bülow S, Burn J, Capella G, Colas C, Friedl W, Møller P, Hes FJ, Järvinen H, Mecklin JP, Nagengast FM, Parc Y, Phillips RK, Hyer W, Ponz de Leon M, Renkonen-Sinisalo L, Sampson JR, Stormorken A, Tejpar S, Thomas HJ, Wijnen JT, Clark SK, Hodgson SV
Gut 2010 Jul;59(7):975-86. doi: 10.1136/gut.2009.198499. PMID: 20581245
van Lier MG, Wagner A, Mathus-Vliegen EM, Kuipers EJ, Steyerberg EW, van Leerdam ME
Am J Gastroenterol 2010 Jun;105(6):1258-64; author reply 1265. Epub 2010 Jan 5 doi: 10.1038/ajg.2009.725. [Epub ahead of print] PMID: 20051941
Cienfuegos JA, Baixauli J, Zozaya G, Bueno A, Arredondo J, Regueira FM, Angós R, Hernández-Lizoáin JL, Idoate MA
Rev Esp Enferm Dig 2009 Dec;101(12):875-9. PMID: 20082550

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