RT Book, Section
A1 Malcolm, William F.
SR Print(0)
ID 1105545570
T1 Down Syndrome
T2 Beyond the NICU: Comprehensive Care of the High-Risk Infant
YR 2015
FD 2015
PB McGraw-Hill Education
PP New York, NY
SN 978-0-07-174858-2
LK accesspediatrics.mhmedical.com/content.aspx?aid=1105545570
RD 2024/04/19
AB DefinitionIn  the  mid-1800s  several  physicians  described  groups  of  patients  who  had  intellectual  disability,  short  stature,  and  specific  facial  characteristics  including  upslanting  palpebral  fissures,  epicanthal  folds,  flat  nasal  bridge,  and  protruding  tongue.Subsequently,  J.  Langdon  Down,  after  whom  Down  syndrome  (DS)  was  named,  emphasized  that  affected  individuals  could  be  distinguished  from  the  heterogeneous  group  of  all  those  with  intellectual  disabilities  based  on  their  unique  physical  features.Unlike  other  genetic  conditions,  individuals  with  DS  are  typically  diagnosed  in  the  newborn  period  based  on  these  distinctive  physical  characteristics.Clinical  syndrome  is  phenotype  of  individuals  with  Trisomy  21.IncidenceDS,  or  trisomy  21,  is  the  most  common  genetic  cause  of  intellectual  disability,  occurring  in  one  in  691  live  births.DS  occurs  in  all  ethnic  groups,  socioeconomic  levels,  and  geographic  regions.Once  the  medical  complications  at  birth  are  appropriately  treated,  individuals  with  DS  can  live  well  into  their  60s  and  beyond  with  productive  lives  if  appropriate  educational,  medical,  and  societal  resources  are  provided.PathophysiologyDS  is  described  as  the  presence  of  an  additional  (third)  copy  of  the  genetic  material  located  on  the  21st  chromosome.The  typical  human  karyotype  is  composed  of  46  chromosomes,  which  group  into  23  pairs.  The  first  22  pairs  of  chromosomes  are  known  as  the  autosomes.  The  last  pair,  composed  of  the  X  chromosome  and/or  the  Y  chromosome,  is  known  as  the  sex  chromosomes.  Females  will  have  two  X  chromosomes,  while  males  will  have  one  X  chromosome  and  one  Y  chromosome.DS  can  occur  in  one  of  three  ways.NondisjunctionDS  due  to  nondisjunction,  also  known  as  standard  trisomy  21,  occurs  when  like  chromosomes  fail  to  separate  during  meiotic  division.  This  results  in  the  egg  or  sperm  cell  contributing  two  copies  of  chromosome  21,  producing  a  child  with  three  complete  copies  of  the  21st  chromosome.Standard  trisomy  21  is  the  most  common  form  of  DS,  accounting  for  95%  of  all  known  cases.The  recurrence  risk  for  parents  of  a  child  with  standard  trisomy  21  is  1%  or  one  in  100,  until  the  maternal  age–related  risk  for  having  a  child  with  a  chromosomal  variation  exceeds  1%  (>38  y/o).The  karyotype  for  an  individual  with  standard  trisomy  21  will  be  47,XY,+21  in  males  or  47,XX,+21  in  females.Robertsonian  translocationDS  due  to  a  Robertsonian  translocation  occurs  when  an  individual  inherits  a  complete  copy  of  the  21st  chromosome  from  each  parent,  as  well  as,  a  copy  of  the  long  arm  of  the  21st  chromosome  fused  to  the  long  arm  of  another  acrocentric  chromosome  (chromosome  13,  14,  15,  21,  or  22).DS  due  to  a  Robertsonian  translocation  accounts  for  3%  to  4%  of  all  known  cases.The  recurrence  risk  for  parents  of  a  child  with  a  Robertsonian  translocation  can  vary  between  0.5%  and  100%  depending  on  which  parent  is  the  carrier  of  the  balanced  translocation,  as  well  as  which  acrocentric  chromosome  was  involved.  Thus,  it  is  important  that  parental  chromosome  karyotype  analysis  be  performed  prior  to  providing  a  recurrence  risk.The  karyotype  for  an  individual  with  DS  due  to  a  Robertsonian  translocation  would  be  46,XY,der(N;21)(q10;q10)  or  46,XX,der(N;21)(q10;q10),  where  N  can  be  any  of  the  acrocentric  chromosomes  (chromosome  13,  14,  15,  21,  or  22).MosaicismMosaic  DS  occurs  when  one  chromosome  fails  ...