EP18.36: A new fetal sonographic characteristics of Baraitser–Winter cerebrofrontofacial syndrome with ACTB mutation: pulmonary stenosis

Baraitser–Winter Cerebrofrontofacial syndrome (BWCFF) is a multiple congenital anomaly syndrome, with less than 50 cases have been reported in medical literatures. The main manifestations are characteristic craniofacial features, structural brain abnormalities, various degree of mental retardation, short stature, coloboma, sensorineural hearing loss, cardiac defects and renal system abnormalities. All pathogenic variants associated with BWCFF reported to date are gain-of-abnormal-function missense variants in ACTB or ACTG1. β- and γ-actin, a family of essential cytoskeletal proteins, are encoded by ACTB and ACTG1,respectively. Among six human genes encoding actin, only ACTB and ACTG1 are ubiquitously expressed, and the remaining four are expressed primarily in muscle. A 32-year-old woman (gravida 2, para 0) was referred to our clinical centre for fetal pulmonary stenosis with incomplete closure and ventricular septal defect. During the prenatal multidisciplinary consultation, ultrasound screening found both renal pelvises were approximately 0.57/0.64cm in diameter anteriorly and posteriorly, with two to three separated calyces, the wider of which is about 0.4cm, NIPT showed low risk for trisomy 18, trisomy 13 and trisomy 21. A novel heterozygous likely pathogenic missense variant: ACTB: c.645G>T was detected by prenatal trio WES. Herein, we reported a case of fetal pulmonary stenosis combined with renal pelvis separation, with ACTB mutation detected by the trio WES. To our knowledge, this is the first report the fetal pulmonary stenosis in BWCFF syndrome caused by an ACTB mutation, which will broaden the phenotypic spectrum in patients with BWCFF syndrome caused by the ACTB gene. Our report reminds clinicians of BWCFF syndrome in fetuses with severe heart defects and renal pelvis separation and of trio-WES to prenatal diagnosis to screen for associated genetic disorders.