RT Book, Section
A1 Eggert, Stacey L.
A1 Morton, Cynthia C.
A2 Murray, Michael F.
A2 Babyatsky, Mark W.
A2 Giovanni, Monica A.
A2 Alkuraya, Fowzan S.
A2 Stewart, Douglas R.
SR Print(0)
ID 1102703952
T1 Uterine Leiomyomata
T2 Clinical Genomics: Practical Applications in Adult Patient Care
YR 2014
FD 2014
PB McGraw-Hill Education
PP New York, NY
SN 9780071622448
LK accessmedicine.mhmedical.com/content.aspx?aid=1102703952
RD 2024/04/19
AB Disease  summary:Uterine  leiomyomata  (UL)  are  benign  tumors  of  the  uterine  myometrium.UL  are  classified  by  tumor  location  within  the  uterus:  subserosal,  intramural,  and  submucosal.The  prevalence  of  UL  is  estimated  around  75%  for  women  of  reproductive  age.Approximately  25%  of  women  of  reproductive  age  have  symptoms  related  to  UL.  These  symptoms  include  menorrhagia,  pelvic  pressure,  infertility,  and  a  range  of  complications  during  pregnancy.UL  are  hormonally  dependent  tumors  and  are  not  observed  prior  to  puberty.  Estrogen,  progesterone,  and  other  small  growth  factors  promote  tumor  growth.  UL  may  regress  at  menopause.Rarely,  estimated  at  0.1%,  UL  may  progress  to  their  malignant  counterpart,  uterine  leiomyosarcoma  (LMS).Differential  diagnosis:Adenomyosis,  solid  adnexal  mass,  focal  myometrial  contraction,  and  LMSMonogenic  forms:Hereditary  leiomyomatosis  and  renal  cell  cancer  (HLRCC)  is  a  disorder  that  predisposes  the  carrier  to  renal  cell  cancer  and  UL.  HLRCC  is  caused  by  mutations  in  the  FH  gene  encoding  fumarate  hydratase,  an  enzyme  involved  in  the  citric  acid  cycle.Family  history:There  is  evidence  of  genetic  liability  for  UL.  First-degree  relatives  of  an  affected  individual  are  2.2  times  more  likely  to  also  have  UL.Twin  studies:Monozygotic  (MZ)  twins  have  about  twice  the  rate  of  hospitalization  due  to  UL  when  compared  to  dizygotic  (DZ)  twins,  and  the  correlation  for  hysterectomy  in  MZ  twins  is  about  twice  that  observed  in  DZ  twins.Environmental  factors:Early-life  exposure  to  diethylstilbestrol  (DES),  a  synthetic  estrogen,  has  been  associated  with  the  development  of  UL.  Other  conditions  that  affect  estrogen  levels  in  the  body,  including  parity  and  obesity,  are  also  linked  to  UL  growth.Genome-wide  associations:A  genome-wide  linkage  analysis  for  nonsyndromic  UL  has  identified  multiple  linkage  peaks  with  significant  LOD  scores.  Fine  mapping  in  two  replication  populations  detected  several  markers  in  17q25.3  associated  with  UL  diagnosis.  The  associated  markers  are  in  linkage  disequilibrium  with  each  other  including  the  genes  FASN,  CCDC57  and  SLC16A3.  Functional  studies  are  required  to  elucidate  the  possible  role  of  these  genomic  regions  in  UL  predisposition.Pharmacogenomics:Pharmacogenomics  do  not  yet  play  a  role  in  UL  management.