RT Book, Section
A1 Jamal, Seema
A1 Milunksy, Jeffrey M.
A2 Murray, Michael F.
A2 Babyatsky, Mark W.
A2 Giovanni, Monica A.
A2 Alkuraya, Fowzan S.
A2 Stewart, Douglas R.
SR Print(0)
ID 1102706427
T1 Waardenburg Syndrome
T2 Clinical Genomics: Practical Applications in Adult Patient Care
YR 2014
FD 2014
PB McGraw-Hill Education
PP New York, NY
SN 9780071622448
LK accessbiomedicalscience.mhmedical.com/content.aspx?aid=1102706427
RD 2024/04/16
AB Disease  summary:Waardenburg  syndrome  types  1  to  4  are  a  group  of  auditory-pigmentary  syndromes  that  comprise  sensorineural  hearing  loss  (due  to  the  absence  of  melanocytes  in  the  stria  vascularis  of  the  cochlea),  and  hypomelanosis  of  the  eyes,  hair,  and/or  skin.Since  Waardenburg  syndrome  types  1  to  4  are  disorders  related  to  neural  crest  cells  and  their  derivatives,  they  are  considered  to  be  neurocristopathies.Hereditary  basis:Waardenburg  syndrome  is  one  of  the  most  common  syndromic  causes  of  hearing  loss  and  accounts  for  approximately  2%  to  5%  of  all  congenital  sensorineural  hearing  loss.Waardenburg  syndrome  demonstrates  both  inter-  and  intrafamilial  variable  expressivity,  as  well  as  locus  and  allelic  heterogeneity.Waardenburg  syndrome  type  1  (WS1),  Waardenburg  syndrome  type  2  (WS2),  and  Waardenburg  syndrome  type  3  (WS3)  are  transmitted  in  an  autosomal  dominant  manner,  while  Waardenburg  syndrome  type  4  (WS4)  is  inherited  either  as  an  autosomal  recessive  condition,  with  mutations  within  the  endothelin-3  (EDN3)  or  endothelin-B  receptor  (EDNRB)  genes,  or  as  an  autosomal  dominant  condition  with  heterozygous  mutations  within  the  SRY-related  HMG-box  10  (SOX10)  gene.Differential  diagnosis:Well  over  400  genetic  syndromes  that  include  hearing  loss  have  been  described.  While  nonsyndromic  hearing  loss  accounts  for  the  vast  majority  of  hearing  loss,  syndromic  hearing  impairment  is  thought  to  account  for  up  to  30%  of  prelingual  deafness.Piebaldism  [MIM  172800]  is  an  autosomal  dominant  condition  that  has  a  clinical  phenotype  similar  to  that  of  Waardenburg  syndrome.  A  white  forelock  is  commonly  seen  along  with  absent  pigmentation  of  the  medial  forehead,  eyebrows,  chest,  abdomen,  and  limbs.  A  characteristic  feature  is  hyperpigmented  borders  surrounding  the  hypopigmented  areas.  In  contrast  to  Waardenburg  syndrome,  hearing  loss  is  not  characteristic  of  this  syndrome.Tietze  syndrome  [MIM  103500]  is  an  autosomal  dominant  condition  characterized  by  congenital  hearing  loss  and  uniform  hypopigmentation.  Tietze  syndrome  is  allelic  to  WS2  with  heterozygous  mutations  within  the  MITF  gene  described  in  affected  individuals.  In  contrast  to  WS2,  the  Tietze  phenotype  does  not  include  heterochromia.Craniofacial-deafness-hand  syndrome  [MIM  122880]  is  an  autosomal  dominant  condition  with  characteristic  facial  features,  profound  sensorineural  hearing  loss,  and  radiologic  abnormalities  of  the  maxilla,  nasal  bones,  and  hands.  This  condition  is  also  allelic  to  WS1  and  WS3  with  a  heterozygous  mutation  within  the  PAX3  gene  described  in  an  affected  individual.