OP32.05: Prenatal diagnosis of neonatal Marfan syndrome

Abstract

Marfan syndrome (MS) is a rare disease of the connective tissue. Neonatal MS is even rarer, and rarer still is its prenatal ultrasound diagnosis with 7 cases reported and only 1 surviving patient. We describe 2 new cases. Both had no relevant family history, had normal scans in the first half of pregnancy, were referred because of fetal cardiomegaly at 28 and 35 weeks respectively, and were delivered at term. Case 1: Fetal echocardiography showed severe cardiomegaly, dilation of the initial portion of the great vessels and mild prolapse of the atrioventricular (AV) valve leaflets. Postnatally, a marfanoid habitus was found and a moderate insufficiency of the AV and semilunar valves was also seen. The neonate was discharged on the 7 th day and an angiotensin II receptor antagonist (Losartan) was prescribed to prevent aortic root dilation. Echocardiography at 2 months revealed severe AV valve insufficiency. Rapid worsening required AV valve surgical repair, but the patient died 5 days later. A heterozygous mutation of the fibrillin-1 (FBN1) gene was found. Case 2: Fetal echocardiography showed dilation of the outflow tracts, AV valve insufficiency and redundant AV cusps protruding in the atria during systole. Enlarged and hiperflexed hands and feet were observed. A scan 2 weeks later revealed aortic insufficiency. Postnatally, the same marfanoid habitus was noted. The patient was discharged at 31 days, with Losartan. Two weeks later the patient was readmitted, chest X-ray revealed severe cardiomegaly and emphysematous lungs, and death occurred soon after due to cardiorespiratory arrest. A new mutation of the FBN1 gene was found. The combination of cardiomegaly, enlargement of great vessels and multivalvular regurgitation in the second half of pregnancy may lead to suspect neonatal MF. These valve problems progress relentlessly, leading to heart failure and early death in most cases. This information may be helpful to provide the parents the most accurate counseling. Craniosynostosis is defined as the premature closure of the calvarial sutures and is a feature of many syndromes. Prenatal diagnosis of the syndromic association depends on associated anomalies and molecular analysis of fetal DNA. Abnormal skull shape is the first clue; the earliest reported was at 19 weeks. Carpenter syndrome (CS) is very rare autosomal recessive disorder. We are reporting a case of prenatal diagnosis of CS utilizing 3D ultrasound (3DUS) at 16 weeks of gestation that manifested with craniosynostosis in a family not at risk. A primigravida, first cousin marriage, was referred at 16 weeks of gestation due to marked subcutaneous edema and anomalies. Fetal assessment showed: nuchal thickness of 1.5 cm, abnormal head shape (trapezoid) with suspicion of craniosynostosis. 3D US on skeletal mode suggested premature fusion of metopic and also coronal sutures. It also showed dysmorphic facies-Proptosis, depressed nasal bridge, micrognathia, low set ears, midfacial hypoplasia resulting in abnormal profile. The associated anomalies were: huge o...