The case of Baraitser-Winter cerebrofrontofacial syndrome (BWCFF) reported here involved a ventricular septal defect, which has been previously demonstrated in BWCFF. However, pulmonary valve stenosis has not been previously reported in the literature. Considerable variation in cardiac defects has been observed in BWCFF patients. Congenital heart defects (CHDs), such as ventricular septal defects, bicuspid aortic valves, mitral valve regurgitation, persistent ductus arteriosus and atrial septal defects, have been documented in 12 out of 36 patients with BWCFF(2). These findings suggest that CHD does not exhibit any specific pattern. A pulmonary valve flow rate exceeding 1.4 m/s is used as a diagnostic criterion for foetal pulmonary valve stenosis. Foetal pulmonary valve stenosis is classified as mild, moderate or severe. Mild pulmonary valve stenosis is distinguished by valve thickening and hyperechogenicity, accompanied by systolic flow acceleration or main pulmonary artery dilation. Moderate pulmonary valve stenosis manifests as restricted valve movement and exhibits a varied blood flow pattern at the valve orifice. Severe pulmonary valve stenosis is characterized by the presence of retrograde ductal flow(4). In this study, we present a case of a foetal BWCFF exhibiting severe pulmonary valve stenosis accompanied by retrograde ductal flow. These findings suggested that the prognosis was not favourable.
Subsequently, we present a summary of several scholarly papers discussing cases of BWCFF diagnosed postnatally, accompanied by a retrospective analysis of foetal manifestations. The intrauterine manifestations of BWCFF are nonspecific and diverse.
Di Donato et al. reviewed prenatal ultrasound data for two patients who were diagnosed with BWCFF after birth, both of whom harboured a missense mutation in ACTB. In one patient, prenatal ultrasound indicated an abnormal head shape, hydrops fetalis, hypertelorism and severe polyhydramnios. The other patient exhibited severe prenatal polyhydramnios and hydrops fetalis, with postnatal findings including heart defects (patent ductus arteriosus and ventricular septal defect) and a bilateral cleft lip with cleft palate (5). Verloes et al. reported prenatal presentations of polyhydramnios and nuchal translucency in some BWCFF patients (2). Aiyar et al. reported a case of an infant diagnosed with BWCFF whose prenatal ultrasound revealed an NT of 4.4 mm, an NF of 7.31 mm, thickened ventricular walls, mild ventriculomegaly (11 mm), an interhemispheric cystic structure in the brain, a unilateral cleft lip and palate, a small stomach bubble, a single umbilical artery, and growth restriction (6).
With the increasing popularity of prenatal WES, a growing number of foetuses manifesting structural abnormalities on ultrasound are being prenatally diagnosed with BWCFF. Drury et al. reported a foetus diagnosed with BWCFF via prenatal WES, revealing ultrasound findings of an NT of 9.7 mm and facial abnormalities. The foetus presented with hypertension, generalized hydrops, and a unilateral cleft lip and palate. A de novo mutation of ACTB was identified in the foetus that was not present in either parent(7). Zhang et al. described another case involving a foetus with an NT measuring 9.5 mm that presented with an omphalocele and a large cystic hygroma. WES confirmed a de novo mutation of ACTB, establishing a diagnosis of BWCFF (8).