TY  - CHAP
M1  - Book, Section
TI  - Down Syndrome (Trisomy 21)
A1  - Epstein, Charles J.
A2  - Valle, David L.
A2  - Antonarakis, Stylianos
A2  - Ballabio, Andrea
A2  - Beaudet, Arthur L.
A2  - Mitchell, Grant A.
Y1  - 2019
N1  - 10.1036/ommbid.373
T2  - The Online Metabolic and Molecular Bases of Inherited Disease
AB  - The  salient  clinical  features  of  Down  syndrome  include  several  minor  malformations  or  dysmorphic  features,  which,  while  not  all  are  invariably  present,  together  constitute  the  distinctive  physical  phenotype  of  the  syndrome.  Mental  retardation  and  hypotonia  are  virtually  always  present,  and  congenital  heart  disease  (particularly  endocardial  cushion  defects)  occurs  in  about  40  percent  of  affected  individuals.  Gastrointestinal  anomalies  (especially  duodenal  atresia  and  Hirschsprung  disease)  are  found  in  about  5  percent.There  is  a  wide  range  of  ultimate  intellectual  attainment  and  rate  of  psychomotor  development,  which,  to  some  extent,  may  be  influenced  by  both  environmental  and  genetic  factors.  No  pharmacologic  therapy  as  yet  has  been  shown  to  have  a  beneficial  effect.  The  specific  causes  of  mental  retardation  have  not  been  elucidated,  although  decreased  nerve  cell  densities,  changes  in  phospholipid  composition,  and  alterations  in  certain  electrophysiologic  properties  of  the  brain  and  isolated  neurons  have  been  demonstrated.  The  pathologic,  metabolic,  and  neurochemical  changes  of  Alzheimer  disease  are  present  after  the  third  decade  in  the  brains  of  all  individuals  with  Down  syndrome,  who  also  have  a  progressive  loss  in  cognitive  functions.  Many  develop  a  frank  dementia.There  is  a  fifteen-  to  twentyfold  increase  in  the  incidence  of  leukemia  in  children  with  Down  syndrome,  with  acute  megakaryoblastic  leukemia  being  particularly  frequent  among  cases  of  acute  nonlymphocytic  leukemia.  Leukemoid  reactions  or  transient  leukemia  occurs  in  infants,  as  does  macrocytosis  and  increased  hematocrit.  The  activities  of  several  erythrocyte  and  granulocyte  enzymes  not  coded  for  by  genes  on  chromosome  21  are  increased,  and  hyperuricemia  may  be  present.Males  with  Down  syndrome  are  almost  invariably  infertile,  whereas  females,  while  decreased  in  fertility,  are  often  capable  of  reproduction.  Longitudinal  growth  is  impaired,  and  there  is  an  increased  frequency  of  thyroid  dysfunction  in  newborns  and  of  thyroid  autoantibodies  throughout  life.  A  variety  of  cellular  abnormalities  are  present,  including  enhanced  responses  to  interferon  and  β-adrenergic  agonists,  and  possibly  small  increases  in  sensitivity  to  radiation,  mutagenic  and  carcinogenic  chemicals,  and  viruses.The  principal  causes  of  death  in  Down  syndrome  are  infection,  congenital  heart  disease,  and  malignancy.  Longevity  has  been  steadily  increasing  in  recent  years,  and  the  life  expectancy  for  individuals  without  congenital  heart  disease  may  be  greater  than  60  years.  The  increased  susceptibility  to  infection  appears  to  be  the  result  of  abnormalities  of  the  immune  system,  particularly  in  the  maturation  and  function  of  T  lymphocytes.In  most  instances,  Down  syndrome  results  from  trisomy  21,  the  presence  of  an  extra  chromosome  21  either  free  or  as  part  of  a  robertsonian  fusion  chromosome  or  isochromosome.  Occasional  cases  result  from  triplication  of  just  the  distal  part  of  the  long  arm  of  chromosome  21,  or  from  the  presence  of  trisomy  21/diploid  mosaicism.  Depending  on  the  frequency  and  distribution  of  trisomic  cells,  mosaic  individuals  may  range  from  being  normal  to  having  the  typical  phenotypic  features  of  Down  syndrome.  There  is  a  very  strong  effect  of  maternal  age,  but  not  of  paternal  age,  on  the  incidence  of  trisomy  21.  The  nondisjunction  event  leading  to  the  trisomy  occurs  in  the  mother  about  86  percent  of  the  time,  with  the  maternal  error  being  predominantly  (75  percent)  in  meiosis  I.  Meiosis  ...
SN  - 
PB  - McGraw-Hill Education
CY  - New York, NY
M3  - doi: 10.1036/ommbid.373
Y2  - 2024/04/19
UR  - ommbid.mhmedical.com/content.aspx?aid=1181418811
ER  -