Sensorineural deafness, distinctive facial features, and abnormal cranial bones: a new variant of Waardenburg syndrome?

Am J Med Genet A. 2008 Jul 15;146A(14):1880-5. doi: 10.1002/ajmg.a.32402.


The Waardenburg syndromes (WS) account for approximately 2% of congenital sensorineural deafness. This heterogeneous group of diseases currently can be categorized into four major subtypes (WS types 1-4) on the basis of characteristic clinical features. Multiple genes have been implicated in WS, and mutations in some genes can cause more than one WS subtype. In addition to eye, hair, and skin pigmentary abnormalities, dystopia canthorum and broad nasal bridge are seen in WS type 1. Mutations in the PAX3 gene are responsible for the condition in the majority of these patients. In addition, mutations in PAX3 have been found in WS type 3 that is distinguished by musculoskeletal abnormalities, and in a family with a rare subtype of WS, craniofacial-deafness-hand syndrome (CDHS), characterized by dysmorphic facial features, hand abnormalities, and absent or hypoplastic nasal and wrist bones. Here we describe a woman who shares some, but not all features of WS type 3 and CDHS, and who also has abnormal cranial bones. All sinuses were hypoplastic, and the cochlea were small. No sequence alteration in PAX3 was found. These observations broaden the clinical range of WS and suggest there may be genetic heterogeneity even within the CDHS subtype.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Craniofacial Abnormalities / genetics*
  • Craniofacial Abnormalities / pathology
  • DNA / genetics
  • DNA Mutational Analysis
  • Female
  • Hearing Loss, Sensorineural / congenital
  • Hearing Loss, Sensorineural / genetics*
  • Humans
  • PAX3 Transcription Factor
  • Paired Box Transcription Factors / genetics
  • Paranasal Sinuses / abnormalities
  • Phenotype
  • Waardenburg Syndrome / classification
  • Waardenburg Syndrome / diagnosis*
  • Waardenburg Syndrome / genetics*


  • PAX3 Transcription Factor
  • PAX3 protein, human
  • Paired Box Transcription Factors
  • DNA