Opitz syndrome is genetically heterogeneous, with one locus on Xp22, and a second locus on 22q11.2.
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.
D000015:Abnormalities, Multiple / Q000235:genetics*; D002675:Child, Preschool; D002892:Chromosomes, Human, Pair 22; D005260:Female; D018740:Genetic Heterogeneity; D008040:Genetic Linkage; D006801:Humans; D006972:Hypertelorism / Q000235:genetics*; D007021:Hypospadias / Q000235:genetics; D008126:Lod Score; D008297:Male; D010375:Pedigree; D013577:Syndrome; D014960:X Chromosome