Prenatal Diagnosis of Abnormal Sternum Development and Dilated Aortic Root in a Fetus with a Novel 204 kb Microdeletion of the TGFRB2 Gene

Rebecca A Feldman,Beverly Coleman,Michael T Mennuti,Justin S Brandt

doi:10.4236/ojog.2016.610075

Abstract

The Loeys-Dietz syndrome (LDS) is a connective tissue disorder that is associated with vascular abnormalities, including aggressive aortic aneurysms, as well as skeletal and craniofacial malformations. The molecular mechanism of this syndrome remains to be fully elucidated. In this case, we describe a 29-year-old woman, gravida 2 para 1, who was referred for consultation after urinary tract malformations were observed during her mid-gestation anatomic survey. Following referral to our unit, ultrasound examination of the 21-week fetus was repeated. The fetus was observed to have a dilated aortic root and a poorly ossified sternum with mild pectus deformity. After elective termination, single nucleotide polymorphism microarray testing identified a novel 204 kb microdeletion involving the short arm of chromosome 3. The deleted genetic material included 4 exons of the TGFBR2 gene. Although the phenotype of LDS may be caused by haploinsufficiency of the TGFBR1 or TGFBR2 gene, our experience suggests a more complex picture of LDS. The study of such cases might further elucidate its pathogenesis.

Highlights

The Loeys-Dietz syndrome (LDS) is a connective tissue disorder that is associated with vascular abnormalities, including aggressive aortic aneurysms, as well as skeletal and craniofacial malformations
We believe that the deletion of four exons of the TGFBR2 gene together with a dilated aortic root and the sternal abnormality are consistent with a diagnosis of LDS
Campbell et al states that haploinsufficiency causes a phenotype that is distinct from LDS, but he concludes that longer follow-up is warranted

Summary

Introduction

Feldman et al 602 case series [1] [2] It is associated with vascular abnormalities, including aggressive aortic aneurysms, skeletal malformations, including pectus excavatum and scoliosis, and craniofacial malformations, such as bifid uvula. The prenatal diagnosis of LDS due to a de novo mutation of TGFBR2 in a 19-week fetus with aortic aneurysm was reported shortly after the syndrome was described [6]. The only additional case of prenatal diagnosis involved the finding of a complex congenital heart defect (double outlet right ventricle with interrupted aortic arch) associated with a mutation in TGFBR1 [7]. Our recent experience with the early second trimester detection of an additional fetus with features of LDS, including aortic findings, and deletion of TGFBR2 (rather than a mutation), prompted this report

Case Report

Findings

Discussion

Conclusion