Hamartomatous polyps are composed of the normal cellular elements of the gastrointestinal tract, but have a markedly distorted architecture. The hamartomatous ...SkiptomaincontentThankyouforvisitingnature.com.YouareusingabrowserversionwithlimitedsupportforCSS.Toobtainthebestexperience,werecommendyouuseamoreuptodatebrowser(orturnoffcompatibilitymodeinInternetExplorer).Inthemeantime,toensurecontinuedsupport,wearedisplayingthesitewithoutstylesandJavaScript.Advertisementnaturenaturereviewsgastroenterology&hepatologyreviewarticlesarticleAbstractThehamartomatouspolyposissyndromesareaheterogeneousgroupofdisordersthatshareanautosomal-dominantpatternofinheritanceandarecharacterizedbyhamartomatouspolypsofthegastrointestinaltract.Thesesyndromesincludejuvenilepolyposissyndrome,Peutz–JegherssyndromeandthePTENhamartomatumorsyndrome.Thefrequencyandlocationofthepolypsvaryconsiderablyamongsyndromes,asdoestheaffectedpatient'spredispositiontothedevelopmentofgastrointestinalandothermalignancies.Althoughthesyndromesareuncommon,itisimportantforthecliniciantorecognizethesedisordersbecausetheyareassociatedwithconsiderablemorbidityandmortality,notonlyfrommalignancybutalsofromnonmalignantmanifestationssuchasbleeding,intussusception,andbowelobstruction.Eachhamartomatouspolyposissyndromehasitsowndistinctiveorgan-specificmanifestationsandeachrequiresadifferentsurveillancestrategy,whichmakesaccuratediagnosiscrucialforappropriatepatientmanagement.Theavailabilityofclinicalgenetictestingforthesedisordersmeansthatappropriaterecognitionallowsfortimelyreferralforcancergeneticcounseling,andoftenallowsforpredicativetestinginat-riskfamilymembers.Promisingly,anunderstandingofthemolecularpathogenesisofthesedisordersoffersinsightsintothemechanismsunderlyingthedevelopmentofsporadicmalignancy,andenablesrationalselectionoftargetedtherapiesthatwarrantfurtherinvestigation.KeyPointsHamartomatouspolyposissyndromesareinheritedautosomal-dominantsyndromesthatconferpredispositiontocancersandhavedivergentclinicalfeatur