Case report：A new foetal sonographic characteristic of Baraitser–Winter cerebrofrontofacial syndrome with ACTB mutation

Abstract

Background Baraitser-Winter cerebrofrontofacial syndrome (BWCFF) is a complex, rare developmental syndrome characterized by craniofacial, visceral, and muscular manifestations. Diagnosis of BWCFF usually occurs postnatally; however, with the widespread application of prenatal trio whole-exome sequencing (WES), it is now possible to diagnose BWCFF prenatally. Case presentation A pregnant woman was found to carry a foetus with pulmonary valve stenosis and renal pelvic separation, and prenatal diagnosis was performed. The pregnant woman underwent amniocentesis to collect amniotic fluid for karyotyping, chromosomal microarray analysis (CMA) and trio WES. Simultaneously, peripheral blood samples were obtained from the woman and her husband for trio WES and Sanger sequencing. The foetal karyotype was normal, and CMA did not reveal any abnormalities. WES identified a heterozygous missense mutation in ACTB (NM_001101.5; c.645G>T) in the foetus. The mutation was classified as likely pathogenic. Sanger sequencing revealed the absence of the mutation in either parent. Conclusions This case report presents an instance of foetal pulmonary valve stenosis coupled with renal pelvis separation, where trio WES identified an ACTB (NM_001101.5; c.645G>T) mutation. This is the first case in which foetal pulmonary valve stenosis was associated with BWCFF linked to an ACTB mutation.