Novel SOX9 Gene Variant Associated with Campomelic Dysplasia: Effects on Sex Phenotypes

Campomelic dysplasia (CD) is a rare autosomal dominant genetic disorder primarily caused by mutations in the SOX9 gene. While this condition can affect multiple organ systems, it mainly influences skeletal and sexual development, leading to skeletal malformations and gonadal dysgenesis. We present two cases of CD diagnosed at an early age. Their clinical presentations were characteristic of this disorder, including bowing of the lower extremities, pretibial dimples, Pierre Robin sequence, and bilateral clubfoot. Both cases exhibited delays in motor skills and speech. The first case involved a 46,XY sex-reversed infant with a novel heterozygous SOX9 gene substitution of p.Arg107Gly (NM_000346.4:c.319C>G). The second case involved a 1.5-year-old boy with typical male external genitalia carrying a heterozygous p.Ala116Val variant (c.347C>T) in the SOX9 gene. Both variants were located in the high mobility group domain of the gene. Two variants, the novel p.Arg107Gly and the p.Ala116Var, in the SOX9 gene were reported to be associated with CD. Despite being in the same domain, these variants lead to different sex phenotypes.