title: JP-HHT phenotype in Danish patients with SMAD4 mutations.
abstract: Patients with germline mutations in SMAD4 can present symptoms of both juvenile polyposis syndrome (JPS) and hereditary hemorrhagic telangiectasia (HHT): the JP-HHT syndrome. The complete phenotypic picture of this syndrome is only just emerging. We describe the clinical characteristics of 14 patients with SMAD4-mutations. The study was a retrospective, register-based study. SMAD4 mutations carriers were identified through the Danish HHT-registry, the genetic laboratories - and the genetic departments in Denmark. The medical files from relevant departments were reviewed and symptoms of HHT, JPS, aortopathy and family history were noted. We detected 14 patients with SMAD4 mutations. All patients had polyps removed and 11 of 14 fulfilled the diagnostic criteria for JPS. Eight patients were screened for HHT-symptoms and seven of these fulfilled the Curaçao criteria. One patient had aortic root dilation. Our findings support that SMAD4 mutations carriers have symptoms of both HHT and JPS and that the frequency of PAVM and gastric involvement with polyps is higher than in patients with HHT or JPS not caused by a SMAD4 mutation. Out of eight patients screened for aortopathy, one had aortic root dilatation, highlighting the need for additional screening for aortopathy.
authors.affiliation: Department of Clinical Genetics, Odense University Hospital, Odense, Denmark.|Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.
authors.forename: A M
authors.initials: AM
authors.lastname: Jelsig
authors.affiliation: Department of Clinical Genetics, Odense University Hospital, Odense, Denmark.
authors.forename: P M
authors.initials: PM
authors.lastname: Tørring
authors.affiliation: Department of Otorhinolaryngology Head and Neck Surgery, HHT-Center, Odense, Denmark.
authors.forename: A D
authors.initials: AD
authors.lastname: Kjeldsen
authors.affiliation: Department of Surgery, Odense University Hospital, Odense, Denmark.
authors.forename: N
authors.initials: N
authors.lastname: Qvist
authors.affiliation: Department of Clinical Genetics, Vejle Hospital, Lillebaelt Hospital, Vejle, Denmark.|Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark.
authors.forename: A
authors.initials: A
authors.lastname: Bojesen
authors.affiliation: Department of Clinical Genetics, Aarhus University Hospital, Aarhus, Denmark.|Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark.
authors.forename: U B
authors.initials: UB
authors.lastname: Jensen
authors.affiliation: Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet, Denmark.
authors.forename: M K
authors.initials: MK
authors.lastname: Andersen
authors.affiliation: Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet, Denmark.
authors.forename: A M
authors.initials: AM
authors.lastname: Gerdes
authors.affiliation: Department of Clinical Genetics, Odense University Hospital, Odense, Denmark.|Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.
authors.forename: K
authors.initials: K
authors.lastname: Brusgaard
authors.affiliation: Department of Clinical Genetics, Odense University Hospital, Odense, Denmark.|Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.
authors.forename: L B
authors.initials: LB
authors.lastname: Ousager
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D003718:Denmark; D005260:Female; D015870:Gene Expression; D006579:Heterozygote; D006801:Humans; D044483:Intestinal Polyposis / Q000150:complications / Q000151:congenital* / Q000175:diagnosis / Q000235:genetics / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009386:Neoplastic Syndromes, Hereditary / Q000150:complications / Q000175:diagnosis / Q000235:genetics* / Q000601:surgery; D010641:Phenotype; D012042:Registries; D012189:Retrospective Studies; D051901:Smad4 Protein / Q000235:genetics*; D013683:Telangiectasia, Hereditary Hemorrhagic / Q000150:complications / Q000175:diagnosis / Q000235:genetics* / Q000601:surgery
chemical_list: C497796:SMAD4 protein, human; D051901:Smad4 Protein
keywords: Osler-Rendu disease; Smad4 protein; Smad4-related juvenile polyposis; epistaxis; hereditary hemorrhagic telangiectasia; juvenile polyposis syndrome; melena