TY  - CHAP
M1  - Book, Section
TI  - Rubinstein-Taybi Syndrome
A1  - Petrij, Fred
A1  - Giles, Rachel H.
A1  - Breuning, Martijn H.
A1  - Hennekam, Raoul C. M.
A2  - Valle, David L.
A2  - Antonarakis, Stylianos
A2  - Ballabio, Andrea
A2  - Beaudet, Arthur L.
A2  - Mitchell, Grant A.
PY  - 2019
T2  - The Online Metabolic and Molecular Bases of Inherited Disease
AB  - The  Rubinstein-Taybi  syndrome  (RTS)  is  a  well-defined  syndrome  with  a  characteristic  face,  broad  thumbs,  broad  big  toes,  and  mental  retardation  as  its  major  clinical  hallmarks.  RTS  is  generally  a  de  novo-occurring  autosomal  dominant  trait.  The  empirical  recurrence  risk  for  a  couple  with  a  previous  child  with  RTS  is  as  low  as  0.1  percent.  If,  however,  a  person  with  RTS  is  able  to  reproduce,  the  recurrence  risk  could  be  as  high  as  50  percent.  Birth  prevalence  is  1  in  100,000  to  125,000.  RTS  has  been  described  in  populations  of  many  different  ancestries,  but  the  number  of  reports  on  non-Caucasian  patients  is  low.The  main  clinical  features  of  the  syndrome  are  abnormalities  of  the  face,  thumbs,  and  big  toes,  as  well  as  growth  and  mental  retardation.  The  facial  appearance  is  striking:  microcephaly,  downslanting  palpebral  fissures,  broad  nasal  bridge,  beaked  nose  with  the  nasal  septum  extending  below  the  alae,  highly  arched  palate,  and  mild  micrognathia.  Broad  thumbs  and  broad  big  toes  are  present  in  almost  all  cases.  Terminal  broadening  of  the  phalanges  of  the  fingers,  persistent  fetal  pads,  clinodactyly  of  the  fifth  finger,  overlapping  of  the  toes,  and  angulation  deformities  of  the  thumbs  and  halluces  can  also  be  present.  There  is  a  marked  growth  retardation  with  poor  weight  gain  during  infancy,  often  replaced  by  being  overweight  in  later  childhood.  Global  mental  deficiency  is  characteristic  with  an  average  IQ  between  35  and  50.  Short  attention  span,  poor  coordination,  and  sudden  mood  changes  characterize  the  behavior  of  RTS  patients.  Other  findings  may  include  eye  anomalies  (nasolacrimal  duct  obstruction,  ptosis  of  eyelids,  congenital  or  juvenile  glaucoma,  and  refractive  errors),  specific  dental  anomalies  (talon  cusps  of  the  permanent  incisors),  a  variety  of  congenital  heart  defects,  and  skin  anomalies  (supernumerary  nipples,  nevus  flammeus,  hirsutism,  and  keloid  formation).  The  clinical  history  often  shows  feeding  problems  and  recurrent  conjunctivitis  in  the  neonatal  period,  respiratory  problems  in  the  first  decade,  and  life-long  constipation.  In  general,  RTS  patients  are  in  good  health.  Although  an  increased  risk  for  different  types  of  tumors  is  known,  life  expectancy  seems  to  be  normal.The  diagnosis  is  based  on  the  clinical  presentation.  Combined  cytogenetic  and  molecular  investigations  of  the  CREB-binding  protein  (CBP)  gene  area  on  chromosome  16p13.3  can  confirm  the  diagnosis  in  15  to  20  percent  of  the  cases.  Gross  chromosomal  rearrangements  such  as  translocations  and  inversions  are  rarely  found,  whereas  microdeletions  occur  in  approximately  10  percent  of  cases.  Point  mutations  in  the  CBP  gene  leading  to  premature  translation-termination  are  reported  as  well.  Heterogeneity  is  expected,  but  no  reports  on  involvement  of  other  genes  have  yet  been  published.The  CREB-binding  protein  functions  as  a  transcriptional  cofactor  by  forming  a  physical  bridge  between  the  different  components  of  the  transcription  machinery.  It  also  functions  as  a  potent  histone  acetyltransferase,  making  the  DNA  accessible  to  transcription  factors.  Furthermore,  it  is  a  mediator  of  different  signaling  pathways  and  participates  in  basic  cellular  functions  such  as  DNA  repair,  cell  growth,  cell  differentiation,  apoptosis,  and  tumor  suppression.  CBP  is  at  the  center  of  multiple  signal  transduction  pathways  and  thereby  regulates  the  expression  of  many  genes.Animal  models  and  biochemical  ...
SN  - 
PB  - McGraw-Hill Education
CY  - New York, NY
Y2  - 2024/04/19
UR  - ommbid.mhmedical.com/content.aspx?aid=1184072273
ER  -