2007/06/01 by R. Stadié, A. Geipel, A Geipel +7
Biochemistry, Genetics and Molecular Biology · Medicine · #Aortic Disease and Treatment Approaches #Cardiovascular Issues in Pregnancy #Connective tissue disorders research
paper · pdf · doi:10.1002/uog.4011
openalex publication_date 2007/06/01 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/30
A healthy 34-year-old woman, gravida 2 para 1, with an uneventful previous pregnancy presented at 22 weeks' gestation with fetal bilateral choroid plexus cysts, mild tricuspid regurgitation and a femur length above the 95th percentile. At 32 weeks the fetus showed massive cardiomegaly, dilatation of the aortic root (Figure 1), bilateral atrioventricular valve insufficiency, mild pulmonary and aortic regurgitation as well as the previously diagnosed femur length above the 95th percentile. The presumptive diagnosis of congenital Marfan syndrome (MS) was made. The parents were counseled regarding the poor prognosis and opted for transplacental digitalization as the only possible intrauterine treatment option. Short-axis ultrasound image of the fetus with Marfan syndrome at 32 weeks' gestation demonstrating cardiomegaly and dilated root of the ascending aorta (AA). RA, right atrium; RV, right ventricle; SP, spine. At 34 weeks' gestation an increased pulsatility of the ductus venosus indicated congestive heart failure and delivery by Cesarean section was performed 48 h after induction of lung maturation. The female neonate presented a typical marfanoid habitus with cutis laxa, arachnodactyly and flexion contractures (Figure 2). Despite all supportive measures the congestive heart failure worsened and the neonate died on the ninth postnatal day. Photographs of the neonate on the second postnatal day demonstrating the typical features of Marfan syndrome: senile appearance due to skin folding, arachnodactyly and an elongated stature. MS is a rare (1–3/10 0001) autosomal dominant disorder based on mutations in a gene located on chromosome 15q21.1 causing a fibrillinopathy which affects the musculoskeletal, occular and cardiovasular systems2. Usually the disease is not recognized until late childhood or early adulthood as symptoms are not manifest before this time. Neonatal MS is a very rare and severe form of this syndrome. Clinical findings are much more severe with some additional manifestations such as congestive heart failure, mitral or tricuspid insufficiency, lobar emphysema, flexion contractures and senile appearance caused by loose skin3, 4. Affected individuals often die within the first 2 years of life owing to intractable congestive heart failure3, 4. Only a few cases of survival for more than 2 years have been reported1, 3. Some authors state that neonatal MS is always due to de-novo mutations1, 5, whereas others describe familial cases in a very small percentage6. There are only five previous reports on the prenatal sonographic diagnosis of MS6-10. In one case dating from 1981 the diagnosis was established at 24 weeks because of significantly lengthened limbs in a mother with a previously affected child. No echocardiographic findings were described, but autopsy demonstrated grossly normal cardiac anatomy and only microscopic changes in the aorta9. The four other reported cases were detected at 29, 33, 34 and 37 weeks on the basis of abnormal echocardiographic findings, including cardiomegaly, atrioventricular valve insufficiency and dilatation of the outflow tracts6-8, 10. Biometric data are missing in these reports, but all newborns displayed the typical elongated stature associated with MS. One pregnancy was terminated, one fetus died in utero and two died neonatally. Based on these reports and our own it is hard to speculate about the onset of sonographically detectable symptoms of MS over the course of pregnancy. In our case, the only possible sonographic markers at 22 weeks' gestation were a femur length > 95th percentile and mild tricuspid regurgitation; however, a presumptive diagnosis was missed as the parents did not show any signs of MS. In contrast, more than 20 years ago, the family history prompted the correct diagnosis in a case with similar markers9. Whether the mild tricuspid regurgitation in our case was a coincidence or a causally related finding is therefore difficult to establish as mild tricuspid regurgitation occurs in up to 6% of normal fetuses in the second trimester11. However, it can be suggested from the combined experience of these cases that the cardiac abnormalities in fetuses with MS will most probably be detectable by the end of the second trimester. In summary, prenatal diagnosis of MS might be possible from 20 weeks' gestation based on the marked elongation of the long bones. However, in the absence of an index case the diagnosis will probably be missed in most cases until dilative cardiomyopathy develops in the third trimester. The following material is available from the Journal homepage: http://www.interscience.wiley.com/jpages/0960-7692/suppmat (restricted access) Videoclip S1 Sweep through the fetal heart at 32 weeks' gestation demonstrating massive cardiomegaly in the four-chamber view and a dilated aortic root in the short-axis view. Videoclip S2 Video of the neonate in the intensive care unit on the second day of postnatal life demonstrating the typical features of Marfan syndrome: senile appearance due to skin folding, arachnodactyly and an elongated stature. The heart beats are transmitted through the skin due to massive cardiomegaly. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. R. Stadié*, A. Geipel*, A. Heep , U. Herberg , B. Welker§, U. Gembruch*, C. Berg*, * Department of Obstetrics and Prenatal Medicine, University of Bonn, Bonn, Germany, Department of Neonatology, University of Bonn, Bonn, Germany, Department of Pediatric Cardiology, University of Bonn, Bonn, Germany, § Practice for Prenatal Medicine, Bonn, Germany