Copy number variations analysis in a cohort of 47 fetuses and newborns with congenital diaphragmatic hernia.

OBJECTIVES: The congenital diaphragmatic hernia (CDH), characterized by malformation of the diaphragm and lung hypoplasia, is a common and severe birth defect that affects around 1 in 4000 live births. However, the etiology of most cases of CDH remains unclear. The aim of this study was to perform a retrospective analysis of copy number variations (CNVs) using a high-resolution array comparative genomic hybridization (array-CGH) in a cohort of fetuses and newborns with CDH. METHODS: Forty seven fetuses and newborns with either isolated or syndromic CDH were analyzed by oligonucleotide-based array-CGH Agilent 180K technique. RESULTS: A mean of 10.2 CNVs was detected by proband with a total number of 480 CNVs identified based on five categories: benign, likely benign, of uncertain signification, likely pathogenic, and pathogenic. Diagnostic performance was estimated at 19.15% (i.e., likely pathogenic and pathogenic CNVs) for both CDH types. We identified 11 potential candidate genes: COL25A1, DSEL, EYA1, FLNA, MECOM, NRXN1, RARB, SPATA13, TJP2, XIRP2, and ZFPM2. CONCLUSION: We suggest that COL25A1, DSEL, EYA1, FLNA, MECOM, NRXN1, RARB, SPATA13, TJP2, XIRP2, and ZFPM2 genes may be related to CDH occurrence. Thus, this study provides a possibility for new methods of a positive diagnosis.

Prognosis of Isolated First-Trimester Fetal Megacystis with Spontaneous Resolution.

OBJECTIVE: Fetal megacystis has a poor prognosis. During the first trimester, it is frequently associated with chromosomal abnormalities or multiple malformations, but can also be isolated and resolve spontaneously. In this study, our main objective was to determine the fetal and pediatric prognosis in this particular situation. METHODS: This was a retrospective multicenter study. We describe the cases referred to our fetal medicine centers and also cases previously reported in the international literature. RESULTS: Five cases were referred to our fetal medicine centers. After spontaneous resolution of megacystis, close ultrasound follow-up revealed urinary tract abnormalities in all cases. These abnormalities were all transient. After birth, 1 of the children developed a mild ureteropelvic junction obstruction. Pediatric follow-up was normal for the other children. Our 5 cases plus 79 in the literature mean that 84 cases of isolated first-trimester fetal megacystis with spontaneous resolution have been reported to date. The risk of chromosomal abnormality was 2.4% (2/84) and pediatric follow-up was normal in 96.4% of cases (81/84). CONCLUSION: Even when isolated first-trimester fetal megacystis resolves spontaneously, fetal karyotype analysis and close prenatal ultrasound follow-up should be performed. When there is no chromosomal abnormality, the renal pediatric prognosis seems to be good.