Opitz syndrome is genetically heterogeneous, with one locus on Xp22, and a second locus on 22q11.2

Nat Genet. 1995 Dec;11(4):459-61. doi: 10.1038/ng1295-459.


Opitz syndrome (OS, McKusick 145410) is a well described genetic syndrome affecting multiple organ systems whose cardinal manifestations include widely spaced eyes and hypospadias (Fig. 1). It was first reported as two separate entities, BBB syndrome, and G syndrome. However, subsequent reports of families in which the BBB and G syndrome segregated within a single kindred suggested that they were a single clinical entity. Although the original pedigrees were consistent with X-linked and autosomal dominant inheritance, male-to-male transmission in subsequent reports suggested that OS was inherited as an autosomal dominant trait. Here we report that OS is a heterogeneous disorder, with an X-linked and an autosomal locus. Three families were linked to DXS987 in Xp22, with a lod score of 3.53 at zero recombination. Five families were linked to D22S345 from chromosome 22q11.2, with a lod score of 3.53 at zero recombination. This represents the first classic multiple congenital anomaly syndrome with an X-linked and an autosomal form.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Abnormalities, Multiple / genetics*
  • Child, Preschool
  • Chromosomes, Human, Pair 22*
  • Female
  • Genetic Heterogeneity*
  • Genetic Linkage
  • Humans
  • Hypertelorism / genetics*
  • Hypospadias / genetics
  • Lod Score
  • Male
  • Pedigree
  • Syndrome
  • X Chromosome*