TY  - CHAP
M1  - Book, Section
TI  - Juvenile Polyposis Syndrome
A1  - Howe, James R.
A2  - Valle, David L.
A2  - Antonarakis, Stylianos
A2  - Ballabio, Andrea
A2  - Beaudet, Arthur L.
A2  - Mitchell, Grant A.
Y1  - 2019
N1  - 10.1036/ommbid.336
T2  - The Online Metabolic and Molecular Bases of Inherited Disease
AB  - Juvenile  polyposis  (JP)  is  an  autosomal  dominant  syndrome  characterized  by  multiple  hamartomatous  polyps  of  the  gastrointestinal  (GI)  tract.  Patients  may  have  juvenile  polyps  of  the  stomach,  small  intestine,  and/or  colon.  The  diagnosis  of  JP  is  made  by  having  more  than  five  juvenile  polyps  in  the  colon,  juvenile  polyps  throughout  the  GI  tract,  or  one  or  more  juvenile  polyps  in  the  setting  of  a  family  history  of  JP.  Patients  with  other  genetically  distinct  syndromes  may  also  have  hamartomatous  polyps,  and  these  conditions  need  to  be  excluded  by  careful  history  and  physical  examination.  Due  to  the  association  of  juvenile  polyps  with  several  heterogeneous  syndromes,  it  is  likely  that  there  are  multiple  genes  that  predispose  to  JP.Approximately  20  to  50  percent  of  JP  cases  are  familial,  with  the  remainder  arising  de  novo.  As  many  as  20  percent  of  patients  may  have  associated  anomalies,  which  are  more  common  in  sporadic  cases.  Patients  with  JP  are  at  approximately  50  percent  risk  for  the  developing  GI  cancers,  the  majority  of  which  are  colorectal  cancers,  but  they  are  also  at  risk  for  upper  GI  cancers.The  pathologic  features  of  juvenile  polyps  are  dilated,  cystic  glands,  infiltration  of  the  lamina  propria  by  inflammatory  cells,  and  an  overabundance  of  stroma.  Larger  polyps  may  also  contain  adenomatous  areas;  adenocarcinoma  has  also  been  described  within  juvenile  polyps.  Although  the  exact  mechanism  of  carcinogenesis  is  unclear,  it  has  been  suggested  that  the  changes  seen  in  the  lamina  propria  are  brought  about  through  landscaper  defects,  where  changes  in  this  tissue  layer  lead  to  an  environment  predisposing  to  neoplastic  transformation  of  the  overlying  epithelium.Loss  of  heterozygosity  studies  have  revealed  a  tumor-suppressor  locus  for  JP  on  chromosome  10q22,  with  the  minimal  region  of  overlap  defining  a  3-cM  region  approximately  7  cM  centromeric  to  the  PTEN  gene.  Germ  line  PTEN  mutations  have  been  described  in  four  unrelated  patients  with  JP,  but  it  is  possible  that  some  of  these  patients  had  Cowden  syndrome.A  gene  for  JP  has  been  mapped  to  chromosome  18q21.1  by  genetic  linkage  analysis,  within  an  interval  containing  the  two  tumor-suppressor  genes  DCC  and  DPC4  (Smad4).  Germ  line  mutations  in  one  of  these  genes,  Smad4,  have  been  found  in  6  of  10  familial  and  sporadic  JP  patients.  In  familial  cases,  these  mutations  segregated  with  the  JP  phenotype,  and  all  were  predicted  to  cause  truncation  of  the  Smad4  protein,  resulting  in  loss  of  its  C-terminus  required  for  oligomerization.The  Smad4  gene  consists  of  11  exons  and  encodes  for  552  amino  acids.  Smad4  is  a  common  mediator  for  the  transforming  growth  factor-β,  activin,  and  bone  morphogenetic  protein  signaling  pathways.  The  Smad4  protein  associates  with  other  Smad  proteins  following  their  phosphorylation  by  activated  receptors,  then  translocates  to  the  nucleus  where  it  regulates  transcription  through  direct  binding  to  specific  DNA  sequences.  Smad4  is  required  for  differentiation  of  the  mesoderm  and  visceral  endoderm  during  embryogenesis;  transgenic  mice  with  Smad4  and  Apc  mutations  have  polyps  with  stromal  proliferation  reminiscent  of  juvenile  polyps.  
SN  - 
PB  - McGraw-Hill Education
CY  - New York, NY
M3  - doi: 10.1036/ommbid.336
Y2  - 2024/04/19
UR  - ommbid.mhmedical.com/content.aspx?aid=1181414701
ER  -