BACKGROUND AND GOALS: Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant polyposis syndrome caused by STK11 germline mutations. PJS is associated with an increased risk of cancer. In our cohort, clinical and phenotypic parameters were correlated with genotypic findings and patients were prospectively followed by surveillance. STUDY: Thirty-one patients treated between 2000 and 2006, were evaluated. STK11 genotyping was performed and phenotypes of patients with truncating (TM) and nontruncating mutations (NTM) were compared. RESULTS: Median age at first symptoms was 11 years and complications occurred before the age of ten in 42% of patients. STK11 mutations were detected in 16 of 22 families (12 TM; four NTM). Patients with TM had more surgical gastrointestinal (GI) interventions (p = 0.021), and female patients in the TM group had an increased risk of undergoing gynecological surgery (p = 0.016). Also, there was a trend towards a higher polyp count (p = 0.11) and earlier age at first polypectomy (p = 0.13) in the TM group. Ten carcinomas were detected in six patients resulting in a cancer risk of 65% up to the age of 65 years. Patients with TM tended to develop more cancers (p = 0.10). Importantly, our surveillance strategy used detected 50% of cancers (n = 5) at an early potentially curable stage. CONCLUSIONS: Our study shows that almost half of PJ patients have complications early in life independent of mutational status. Patients with TM require more surgical GI interventions and tend to develop more polyps and cancers. Furthermore, close surveillance detects early stage cancers in patients. We propose that surveillance should be started as early as 8 years in all patients to avoid complications. Moreover, patients with TM may benefit from surveillance at shorter intervals.
BACKGROUND AND GOALS: Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant polyposis syndrome caused by STK11 germline mutations. PJS is associated with an increased risk of cancer. In our cohort, clinical and phenotypic parameters were correlated with genotypic findings and patients were prospectively followed by surveillance. STUDY: Thirty-one patients treated between 2000 and 2006, were evaluated. STK11 genotyping was performed and phenotypes of patients with truncating (TM) and nontruncating mutations (NTM) were compared. RESULTS: Median age at first symptoms was 11 years and complications occurred before the age of ten in 42% of patients. STK11 mutations were detected in 16 of 22 families (12 TM; four NTM). Patients with TM had more surgical gastrointestinal (GI) interventions (p = 0.021), and female patients in the TM group had an increased risk of undergoing gynecological surgery (p = 0.016). Also, there was a trend towards a higher polyp count (p = 0.11) and earlier age at first polypectomy (p = 0.13) in the TM group. Ten carcinomas were detected in six patients resulting in a cancer risk of 65% up to the age of 65 years. Patients with TM tended to develop more cancers (p = 0.10). Importantly, our surveillance strategy used detected 50% of cancers (n = 5) at an early potentially curable stage. CONCLUSIONS: Our study shows that almost half of PJ patients have complications early in life independent of mutational status. Patients with TM require more surgical GI interventions and tend to develop more polyps and cancers. Furthermore, close surveillance detects early stage cancers in patients. We propose that surveillance should be started as early as 8 years in all patients to avoid complications. Moreover, patients with TM may benefit from surveillance at shorter intervals.
Authors: Stefan Aretz; Dietlinde Stienen; Siegfried Uhlhaas; Steffan Loff; Walter Back; Constanze Pagenstecher; D Ross McLeod; Gail E Graham; Elisabeth Mangold; René Santer; Peter Propping; Waltraut Friedl Journal: Hum Mutat Date: 2005-12 Impact factor: 4.878
Authors: Nicholas Hearle; Valérie Schumacher; Fred H Menko; Sylviane Olschwang; Lisa A Boardman; Johan J P Gille; Josbert J Keller; Anne Marie Westerman; Rodney J Scott; Wendy Lim; Jill D Trimbath; Francis M Giardiello; Stephen B Gruber; G Johan A Offerhaus; Felix W M de Rooij; J H Paul Wilson; Anika Hansmann; Gabriela Möslein; Brigitte Royer-Pokora; Tilman Vogel; Robin K S Phillips; Allan D Spigelman; Richard S Houlston Journal: Clin Cancer Res Date: 2006-05-15 Impact factor: 12.531
Authors: N C M Hearle; M F Rudd; W Lim; V Murday; A G Lim; R K Phillips; P W Lee; J O'donohue; P J Morrison; A Norman; S V Hodgson; A Lucassen; R S Houlston Journal: J Med Genet Date: 2006-04 Impact factor: 6.318
Authors: F M Giardiello; S B Welsh; S R Hamilton; G J Offerhaus; A M Gittelsohn; S V Booker; A J Krush; J H Yardley; G D Luk Journal: N Engl J Med Date: 1987-06-11 Impact factor: 91.245
Authors: L A Boardman; S N Thibodeau; D J Schaid; N M Lindor; S K McDonnell; L J Burgart; D A Ahlquist; K C Podratz; M Pittelkow; L C Hartmann Journal: Ann Intern Med Date: 1998-06-01 Impact factor: 25.391
Authors: A M Jelsig; N Qvist; L Sunde; K Brusgaard; Tvo Hansen; F P Wikman; C B Nielsen; I K Nielsen; A M Gerdes; A Bojesen; L B Ousager Journal: Int J Colorectal Dis Date: 2016-03-15 Impact factor: 2.571