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Disease pattern in Danish patients with Peutz-Jeghers syndrome

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International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Purpose

In this paper, we aimed to collect genetic and medical information on all Danish patients with Peutz-Jeghers syndrome (PJS), in order to contribute to the knowledge of phenotype and genotype. Peutz-Jeghers syndrome is a hereditary syndrome characterized by multiple hamartomatous polyps in the GI tract, mucocutaneous pigmentations, and an increased risk of cancer in the GI tract and at extraintestinal sites. Over 90 % of patients harbour a pathogenic mutation in STK11.

Methods

Based on the Danish Pathology Data Bank, the Danish National Patient Register, as well as information from relevant departments at Danish hospitals, we identified patients and collected clinical and genetic information.

Results

We identified 43 patients of which 14 were deceased. The prevalence was estimated to be ∼1 in 195,000 individuals. The median age at first symptom was 27.5 with invagination of the small bowel as the most frequent presenting symptom. We noted 18 occurrences of cancer at various anatomical sites, including a case of thyroid cancer and penile cancer. Eight of the deceased patients had died of cancer. Eighteen different mutations in STK11 had been detected in 28 patients.

Conclusion

This is the first comprehensive study of patients with Peutz-Jeghers syndrome in the Danish population identified from nationwide registers and databases. We have demonstrated that the expressivity of Peutz-Jeghers syndrome varies greatly among the patients, even within the same families, underlining the great phenotypic spectrum. Patients with PJS should be offered surveillance from childhood in order to prevent morbidity and reduce mortality.

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References

  1. Latchford AR, Phillips RK (2011) Gastrointestinal polyps and cancer in Peutz-Jeghers syndrome: clinical aspects. Fam Cancer 10:455–61

    Article  CAS  PubMed  Google Scholar 

  2. Beggs AD, Latchford AR, Vasen HF, Moslein G, Alonso A, Aretz S, Bertario L, Blanco I, Bulow S, Burn J, Capella G, Colas C, Friedl W, Moller P, Hes FJ, Jarvinen 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 (2010) Peutz-Jeghers syndrome: a systematic review and recommendations for management. Gut 59:975–86

    Article  CAS  PubMed  Google Scholar 

  3. Amos CI, Keitheri-Cheteri MB, Sabripour M, Wei C, McGarrity TJ, Seldin MF, Nations L, Lynch PM, Fidder HH, Friedman E, Frazier ML (2004) Genotype-phenotype correlations in Peutz-Jeghers syndrome. J Med Genet 41:327–33

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Choi HS, Park YJ, Youk EG, Yoon KA, Ku JL, Kim NK, Kim SM, Kim YJ, Moon DJ, Min JS, Park CJ, Bae OS, Yang DH, Jun SH, Chung ES, Jung PM, Whang Y, Park JG (2000) Clinical characteristics of Peutz-Jeghers syndrome in Korean polyposis patients. Int J Colorectal Dis 15:35–8

    Article  CAS  PubMed  Google Scholar 

  5. Correa R, Salpea P, Stratakis CA (2015) Carney complex: an update. Eur J Endocrinol 173:85–97

    Article  Google Scholar 

  6. Lampe AK, Hampton PJ, Woodford-Richens K, Tomlinson I, Lawrence CM, Douglas FS (2003) Laugier-Hunziker syndrome: an important differential diagnosis for Peutz-Jeghers syndrome. J Med Genet 40:e77

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Vogel T, Schumacher V, Saleh A, Trojan J, Moslein G (2000) Extraintestinal polyps in Peutz-Jeghers syndrome: presentation of four cases and review of the literature. Deutsche Peutz-Jeghers-Studiengruppe. Int J Colorectal Dis 15:118–23

    Article  CAS  PubMed  Google Scholar 

  8. Aretz S, Stienen D, Uhlhaas S, Loff S, Back W, Pagenstecher C, McLeod DR, Graham GE, Mangold E, Santer R, Propping P, Friedl W (2005) High proportion of large genomic STK11 deletions in Peutz-Jeghers syndrome. Hum Mutat 26:513–9

    Article  CAS  PubMed  Google Scholar 

  9. Hearle N, Schumacher V, Menko FH, Olschwang S, Boardman LA, Gille JJ, Keller JJ, Westerman AM, Scott RJ, Lim W, Trimbath JD, Giardiello FM, Gruber SB, Offerhaus GJ, de Rooij FW, Wilson JH, Hansmann A, Moslein G, Royer-Pokora B, Vogel T, Phillips RK, Spigelman AD, Houlston RS (2006) Frequency and spectrum of cancers in the Peutz-Jeghers syndrome. Clin Cancer Res 12:3209–15

    Article  CAS  PubMed  Google Scholar 

  10. Fan D, Ma C, Zhang H (2009) The molecular mechanisms that underlie the tumor suppressor function of LKB1. Acta Biochim Biophys Sin (Shanghai) 41:97–107

    Article  CAS  Google Scholar 

  11. Giardiello FM, Trimbath JD (2006) Peutz-Jeghers syndrome and management recommendations. Clin Gastroenterol Hepatol 4:408–15

    Article  PubMed  Google Scholar 

  12. Giardiello FM, Brensinger JD, Tersmette AC, Goodman SN, Petersen GM, Booker SV, Cruz-Correa M, Offerhaus JA (2000) Very high risk of cancer in familial Peutz-Jeghers syndrome. Gastroenterology 119:1447–53

    Article  CAS  PubMed  Google Scholar 

  13. Resta N, Pierannunzio D, Lenato GM, Stella A, Capocaccia R, Bagnulo R, Lastella P, Susca FC, Bozzao C, Loconte DC, Sabba 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 (2013) Cancer risk associated with STK11/LKB1 germline mutations in Peutz-Jeghers syndrome patients: results of an Italian multicenter study. Dig Liver Dis 45:606–11

    Article  CAS  PubMed  Google Scholar 

  14. Rebsdorf Pedersen I, Hartvigsen A, Fischer Hansen B, Toftgaard C, Konstantin-Hansen K, Büllow S (1994) Management of Peutz-Jeghers syndrome. Int J Colorectal Dis 9(4):177–9

  15. Lynge E, Sandegaard JL, Rebolj M (2011) The Danish National Patient Register. Scand J Public Health 39:30–3

    Article  PubMed  Google Scholar 

  16. Bjerregaard B, Larsen OB (2011) The Danish Pathology Register. Scand J Public Health 39:72–4

    Article  PubMed  Google Scholar 

  17. Utsunomiya J, Gocho H, Miyanaga T, Hamaguchi E, Kashimure A (1975) Peutz-Jeghers syndrome: its natural course and management. Johns Hopkins Med J 136:71–82

    CAS  PubMed  Google Scholar 

  18. Naitoh H, Sumiyoshi Y, Kumashiro R, Inutsuka S, Fujita K, Yamamoto T, Murayama H (1988) A solitary Peutz-Jeghers type hamartomatous polyp in the duodenum—a case report. Jpn J Surg 18:475–7

    Article  CAS  PubMed  Google Scholar 

  19. Kuwano H, Takano H, Sugimachi K (1989) Solitary Peutz-Jeghers type polyp of the stomach in the absence of familial polyposis coli in a teenage boy. Endoscopy 21:188–90

    Article  CAS  PubMed  Google Scholar 

  20. Kitaoka F, Shiogama T, Mizutani A, Tsurunaga Y, Fukui H, Higami Y, Shimokawa I, Taguchi T, Kanematsu T (2004) A solitary Peutz-Jeghers-type hamartomatous polyp in the duodenum. A case report including results of mutation analysis. Digestion 69:79–82

    Article  PubMed  Google Scholar 

  21. Burkart AL, Sheridan T, Lewin M, Fenton H, Ali NJ, Montgomery E (2007) Do sporadic Peutz-Jeghers polyps exist? Experience of a large teaching hospital. Am J Surg Pathol 31:1209–14

    Article  PubMed  Google Scholar 

  22. Bosman FT (1999) The hamartoma-adenoma-carcinoma sequence. J Pathol 188:1–2

    Article  CAS  PubMed  Google Scholar 

  23. Entius MM, Keller JJ, Westerman AM, van Rees BP, van Velthuysen ML, de Goeij AF, Wilson JH, Giardiello FM, Offerhaus GJ (2001) Molecular genetic alterations in hamartomatous polyps and carcinomas of patients with Peutz-Jeghers syndrome. J Clin Pathol 54:126–31

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Miyaki M, Iijima T, Hosono K, Ishii R, Yasuno M, Mori T, Toi M, Hishima T, Shitara N, Tamura K, Utsunomiya J, Kobayashi N, Kuroki T, Iwama T (2000) Somatic mutations of LKB1 and beta-catenin genes in gastrointestinal polyps from patients with Peutz-Jeghers syndrome. Cancer Res 60:6311–3

    CAS  PubMed  Google Scholar 

  25. Mehenni H, Resta N, Park JG, Miyaki M, Guanti G, Costanza MC (2006) Cancer risks in LKB1 germline mutation carriers. Gut 55:984–90

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Salloch H, Reinacher-Schick A, Schulmann K, Pox C, Willert J, Tannapfel A, Heringlake S, Goecke TO, Aretz S, Stemmler S, Schmiegel W (2010) Truncating mutations in Peutz-Jeghers syndrome are associated with more polyps, surgical interventions and cancers. Int J Colorectal Dis 25:97–107

    Article  PubMed  Google Scholar 

  27. Hearle N, Schumacher V, Menko FH, Olschwang S, Boardman LA, Gille JJ, Keller JJ, Westerman AM, Scott RJ, Lim W, Trimbath JD, Giardiello FM, Gruber SB, Offerhaus GJ, Rooij FW, Wilson JH, Hansmann A, Moslein G, Royer-Pokora B, Vogel T, Phillips RK, Spigelman AD, Houlston RS (2006) STK11 status and intussusception risk in Peutz-Jeghers syndrome. J Med Genet 43:e41

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Wei S, LiVolsi VA, Brose MS, Montone KT, Morrissette JJ, Baloch ZW (2016) STK11 mutation identified in thyroid carcinoma. Endocr Pathol 27:65–9

    Article  CAS  PubMed  Google Scholar 

  29. Syngal S, Brand RE, Church JM, Giardiello FM, Hampel HL, Burt RW (2015) ACG clinical guideline: genetic testing and management of hereditary gastrointestinal cancer syndromes. Am J Gastroenterol 110:223–62, quiz 63

    Article  PubMed  PubMed Central  Google Scholar 

  30. Cairns SR, Scholefield JH, Steele RJ, Dunlop MG, Thomas HJ, Evans GD, Eaden JA, Rutter MD, Atkin WP, Saunders BP, Lucassen A, Jenkins P, Fairclough PD, Woodhouse CR (2010) Guidelines for colorectal cancer screening and surveillance in moderate and high risk groups (update from 2002). Gut 59:666–89

    Article  PubMed  Google Scholar 

  31. Brown G, Fraser C, Schofield G, Taylor S, Bartram C, Phillips R, Saunders B (2006) Video capsule endoscopy in Peutz-Jeghers syndrome: a blinded comparison with barium follow-through for detection of small-bowel polyps. Endoscopy 38:385–90

    Article  CAS  PubMed  Google Scholar 

  32. Postgate A, Hyer W, Phillips R, Gupta A, Burling D, Bartram C, Marshall M, Taylor S, Brown G, Schofield G, Bassett P, Spray C, Fitzpatrick A, Latchford A, Fraser C (2009) Feasibility of video capsule endoscopy in the management of children with Peutz-Jeghers syndrome: a blinded comparison with barium enterography for the detection of small bowel polyps. J Pediatr Gastroenterol Nutr 49:417–23

    Article  PubMed  Google Scholar 

  33. Gupta A, Postgate AJ, Burling D, Ilangovan R, Marshall M, Phillips RK, Clark SK, Fraser CH (2010) A prospective study of MR enterography versus capsule endoscopy for the surveillance of adult patients with Peutz-Jeghers syndrome. AJR Am J Roentgenol 195:108–16

    Article  PubMed  Google Scholar 

  34. Maccioni F, Al Ansari N, Mazzamurro F, Barchetti F, Marini M (2012) Surveillance of patients affected by Peutz-Jeghers syndrome: diagnostic value of MR enterography in prone and supine position. Abdom Imaging 37:279–87

    Article  CAS  PubMed  Google Scholar 

  35. Pennazio M, Spada C, Eliakim R, Keuchel M, May A, Mulder CJ, Rondonotti E, Adler SN, Albert J, Baltes P, Barbaro F, Cellier C, Charton JP, Delvaux M, Despott EJ, Domagk D, Klein A, McAlindon M, Rosa B, Rowse G, Sanders DS, Saurin JC, Sidhu R, Dumonceau JM, Hassan C, Gralnek IM (2015) Small-bowel capsule endoscopy and device-assisted enteroscopy for diagnosis and treatment of small-bowel disorders: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline. Endoscopy 47:352–76

    Article  PubMed  Google Scholar 

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Acknowledgments

We would like to acknowledge Inga R. Pedersen, MD, for contributing to the identification of patients and helping with obtaining medical information. The study was supported by grants from the Region of Southern Denmark, Odense University Hospital: Frie forskningsmidler, and the University of Southern Denmark.

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Authors and Affiliations

  1. Department of Clinical Genetics, Odense University Hospital, Sdr. Boulevard 29, 5000, Odense, Denmark

    A. M. Jelsig, K. Brusgaard & L. B. Ousager

  2. Institute of Clinical Research, University of Southern Denmark, Winsløwparken 19, 3, 5000, Odense, Denmark

    A. M. Jelsig, K. Brusgaard & L. B. Ousager

  3. Department of Surgery A, Odense University Hospital, Sdr. Boulevard 29, 5000, Odense, Denmark

    N. Qvist

  4. Department of Clinical Genetics, Aarhus University Hospital, Brendstrupgaardsvej 21 C, 8200, Aarhus, Denmark

    L. Sunde

  5. Center for Genomic Medicine, Rigshospitalet, University Hospital of Copenhagen, Blegdamsvej 9, 2100, Copenhagen, Denmark

    Tvo Hansen

  6. Department of Molecular Medicine, Aarhus University Hospital, Brendstrupgaardsvej 21 C, 8200, Aarhus, Denmark

    F. P. Wikman

  7. Department of Surgery, Hvidovre Hospital, Kettegårds Alle 30, 2650, Hvidovre, Denmark

    C. B. Nielsen

  8. Department of Clinical Genetics, Aalborg University Hospital, Ladegaardsgade 5, 9000, Aalborg, Denmark

    I. K. Nielsen

  9. Department of Clinical Genetics, University Hospital of Copenhagen, Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen, Denmark

    A. M. Gerdes

  10. Department of Clinical Genetics, Vejle Hospital, Lillebaelt Hospital, Kabbeltoft 25, 7100, Vejle, Denmark

    A. Bojesen

  11. Institute of Regional Health Research, University of Southern Denmark, Winsløwparken 19, 3, 5000, Odense, Denmark

    A. Bojesen

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  1. A. M. Jelsig
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  2. N. Qvist
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  3. L. Sunde
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  8. I. K. Nielsen
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  11. L. B. Ousager
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Correspondence to A. M. Jelsig.

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Jelsig, A.M., Qvist, N., Sunde, L. et al. Disease pattern in Danish patients with Peutz-Jeghers syndrome. Int J Colorectal Dis 31, 997–1004 (2016). https://doi.org/10.1007/s00384-016-2560-3

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  • DOI: https://doi.org/10.1007/s00384-016-2560-3

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