Waardenburg syndrome type 3 (Klein-Waardenburg syndrome) segregating with a heterozygous deletion in the paired box domain of PAX3: a simple variant or a true syndrome?

Clin Genet. 2001 Oct;60(4):301-4. doi: 10.1034/j.1399-0004.2001.600408.x.


Klein-Waardenburg syndrome or Waardenburg syndrome type 3 (WS-III; MIM 148820) is characterized by the presence of musculoskeletal abnormalities in association with clinical features of Waardenburg syndrome type 1 (WS-I). Since the description of the first patient in 1947 (D. Klein, Arch Klaus Stift Vererb Forsch 1947: 22: 336-342), a few cases have been reported. Only occasional families have demonstrated autosomal-dominant inheritance of WS-III. In a previous report, a missense mutation in the paired domain of the PAX3 gene has been described in a family with dominant segregation of WS-III. In this report, we present a second family (mother and son) with typical clinical findings of WS-III segregating with a heterozygous 13-bp deletion in the paired domain of the PAX3 gene. Although homozygosity or compound heterozygosity has also been documented in patients with severe limb involvement, a consistent genotype-phenotype correlation for limb abnormalities associated with heterozygous PAX3 mutations has not previously been apparent. Heterozygous mutations could either reflect a unique dominant-negative effect or possibly the contribution of other unlinked genetic modifiers in determining the phenotype.

Publication types

  • Case Reports

MeSH terms

  • Chromosome Segregation / genetics
  • DNA Mutational Analysis
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / genetics*
  • Exons / genetics
  • Female
  • Genes, Dominant / genetics
  • Genetic Variation / genetics
  • Heterozygote*
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • PAX3 Transcription Factor
  • Paired Box Transcription Factors
  • Pedigree
  • Phenotype
  • Polymorphism, Single-Stranded Conformational
  • Protein Structure, Tertiary
  • Sequence Deletion / genetics*
  • Transcription Factors*
  • Waardenburg Syndrome / genetics*


  • DNA-Binding Proteins
  • PAX3 Transcription Factor
  • PAX3 protein, human
  • Paired Box Transcription Factors
  • Transcription Factors
  • Pax3 protein, mouse