A Whole MED12 Gene Deletion in a Female Fetus With Features Encountered in Hardikar Syndrome

Chromosomal microarray analysis (CMA), methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA), and trio-whole exome sequencing (WES) were performed in a female fetus with omphalocele. A de novo heterozygous 300-kb deletion in the Xq13.1 region, which includes the MED12 gene, was identified. Follow-up ultrasound at 18 weeks of gestation revealed features consistent with Hardikar syndrome (HS), including a right-sided cleft lip and palate, an omphalocele with intestines, a diaphragmatic hernia with the stomach in the left thoracic cavity, and displacement of the heart to the right. Phenotypic evaluation confirmed the presence of a cleft lip and palate as well as umbilical hernia. These findings suggest that a heterozygous deletion of the entire MED12 gene may contribute to the HS phenotype. This case extends the possible damaging effects of haploinsufficiency of the MED12 gene in the pathogenesis of HS.