DiGeorge syndrome chromosome region deletion and duplication: Prenatal genotype-phenotype variability in fetal ultrasound and MRI.

Objective: The aim of the study was to assess genotype-phenotype correlation of prenatally diagnosed fetal DGS and dup22q11 syndrome by fetal molecular genetic analysis, fetal ultrasound, and/or MRI.

Methods: In this retrospective consecutive case series, pregnant women were screened for fetal anomalies during a period of 10 years. Fetal genotype was assessed in 72 cases upon the occurrence of five prenatal fetal phenotypic features: cardiac anomalies, hypo/aplastic thymus, craniofacial malformations, urinary abnormalities, or IUGR; genotype-phenotype correlation was tested to potentially improve prenatal diagnosis of fetal DGS and dup22q11 syndrome.

Results: Fetal genotypes of deletions or duplications in proximal clusters of LCR22s (A-B) were associated with fetal cardiac anomalies in combination with hypo/aplastic thymus and craniofacial malformations, suggesting a correlation with deleted HIRA. TOF associated with aplastic thymus in combination with renal defects indicated a relevant correlation with TBX1 deletion. Deletions in central LCR22s (B-D) with the loss of CRKL supposed a trend of genotype-phenotype correlation with fetal urinary abnormalities.

Conclusion: Genotype-phenotype correlation might improve prenatal diagnosis of fetal DGS and dup22q11 syndrome. Hence, prenatal screening and counseling is highly enhanced by a combination of fetal molecular genetic analysis, fetal ultrasound, and/or MRI. The implications of these findings remain to be explored.