Case presentation
A 30-year-old woman (gravida 1, para 0) with no relevant personal or family medical history and no exposure to any known teratogen was referred to our department for fetal heart screening because of mild fetal tricuspid regurgitation at 24+6 weeks of gestation. Fetal echocardiography (Figure 1) at 26+1weeks of gestation showed the fetal heart was normal (the aortic root was approximately 5.1 mm in diameter, Z score -0.29, and the main pulmonary artery was approximately 5.9 mm in diameter, Z score -0.21). Gene chip microarray analysis was performed at 26+5weeks of gestation, and no abnormal chromosome number or pathogenic copy number variation was found. The child was female and born at 38 weeks. Neonatal echocardiography showed mild tricuspid regurgitation and aortic regurgitation at two days after birth. Regular child health care was planned. However, at three months after birth the aortic sinus was dilated (approximately 20 mm in diameter, Z score 6.1) and mild tricuspid regurgitation was observed. At one year and two months old, physical examination found a prominent forehead, sunken eyes, high palate, slender fingers and pectus carinatum. Cardiac auscultation revealed grade III systolic murmurs in the apical area and the third and fourth intercostal areas. Echocardiography (Figure 2) showed cardiomegaly and continuation of dilated aortic sinus (approximately 28 mm in diameter, Z score 7.1). The mitral and tricuspid valve leaflets were thickened, elongated and billowing toward the atrium during systole, complicated with moderate to severe and moderate regurgitation, respectively. According to the echocardiographic findings and physical signs, the diagnosis of Marfan syndrome was considered. Venous blood of the child and her parents were collected for whole-genome sequencing. The child had a single gene mutation in the chromosome 15 gene, fibrillin 1 (FBN1 ), at exon 25:c.3038G>T (p.Gly1013Val). The mutation was not found in the parents. Based on the child’s physical signs, cardiac manifestations, and genetic mutation, the final diagnosis of early-onset Marfan syndrome was made.