Palatoplasty for the Patient With Campomelic Dysplasia—Report of a Case and Review of the Literature

Campomelic dysplasia (CMPD) is a skeletal disorder resulting from SOX9 gene mutations. Palatoplasty is rare due to a high lethality rate in infants from respiratory distress. Our patient had characteristic symptoms of CMPD, including short bowed limbs, macrocephaly, low-set ears, short palpebral fissures, hypertelorism, a flat nasal bridge, a long philtrum, micrognathia, and a cleft palate. We performed a Furlow palatoplasty when the patient was 2 years 9 months of age, after respiratory conditions had stabilized. We reviewed the literature of CMPD cases that underwent palatoplasty and discussed the optimal timing and surgical methods.

Heterozygous deletion of Sox9 in mouse mimics the gonadal sex reversal phenotype associated with campomelic dysplasia in humans

Heterozygous mutations in the human SOX9 gene cause the skeletal malformation syndrome campomelic dysplasia which in 75% of 46,XY individuals is associated with male-to-female sex reversal. While studies in homozygous Sox9 knockout mouse models confirmed that SOX9 is critical for testis development, mice heterozygous for the Sox9-null allele were reported to develop normal testes. This led to the belief that the SOX9 dosage requirement for testis differentiation is different between humans, which often require both alleles, and mice, in which one allele is sufficient. However, in prior studies, gonadal phenotypes in heterozygous Sox9 XY mice were assessed only by either gross morphology, histological staining or analyzed on a mixed genetic background. In this study, we conditionally inactivated Sox9 in somatic cells of developing gonads using the Nr5a1-Cre mouse line on a pure C57BL/6 genetic background. Section and whole-mount immunofluorescence for testicular and ovarian markers showed that XY Sox9 heterozygous gonads developed as ovotestes. Quantitative droplet digital PCR confirmed a 50% reduction of Sox9 mRNA as well as partial sex reversal shown by an upregulation of ovarian genes. Our data show that haploinsufficiency of Sox9 can perturb testis development in mice, suggesting that mice may provide a more accurate model of human disorders/differences of sex development (DSD) than previously thought.