DiGeorge Syndrome Chromosome Region Deletion and Duplication: Prenatal Genotype-Phenotype Variability in Fetal Ultrasound and MRI.

Author information

1: Department of Gynecology and Obstetrics, Sozialmedizinisches Zentrum Ost - Donauspital, Langobardenstraße 122, A-1220, Vienna, Austria.

Abstract

OBJECTIVE:

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 5 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 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 counselling 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.