Antenatal ultrasound features of isolated recurrent copy number variation in 7q11.23 (Williams syndrome and 7q11.23 duplication syndrome)

Abstract

Objective:We aimed to gather fetal cases carrying a 7q11.23 copy number variation (CNV) and collect precise clinical data to broaden knowledge of antenatal features in these syndromes. Methods:We retrospectively recruited unrelated cases with 7q11.23 deletion, known as Williams-Beuren syndrome (WBS), or 7q11.23 duplication who had prenatal ultrasound findings. We collected laboratory and clinical data, fetal ultrasound, cardiac ultrasound and fetal autopsy reports from 18 prenatal diagnostic centers throughout France.Results: 40 fetuses with WBS were collected and the most common features were intra-uterine growth retardation (IUGR) (70.0%, 28/40), cardiovascular defects (30.0%, 12/40), polyhydramnios (17.5%, 7/40) and protruding tongue (15.0%, 6/40).Fetal autopsy reports were available for 11 cases and were compared with ultrasound prenatal features. Four cases of fetuses with 7q11.23 microduplication were collected and prenatal ultrasound signs were variable and often isolated. Conclusion:This work strengthens the fact that 7q11.23 CNVs are associated with a broad spectrum of antenatal presentations. IUGR and cardiovascular defects were the most frequent ultrasound signs. By reporting the biggest series of antenatal WBS, we aim to better delineate distinctive signs in fetuses with 7q11.23 CNVs.

Prenatal genetic diagnosis of Williams-Beuren syndrome with atypical and complex phenotypes using SNP array and whole exome sequencing

“…The clinical phenotypes of WBS mainly include malformations of the cardiovascular system, peculiar facial features, connective tissue abnormalities, endocrine abnormalities, growth, and mental retardation, and cognitive di culties [13] . Only about 100 cases of prenatally diagnosed WBS have been reported in the literature [10,11,[14][15][16][17] , and most of the WBS cases were diagnosed after birth. An important reason is that the phenotypes of WBS cases are atypical or incomplete in the fetal period, resulting in missed prenatal diagnosis.…”