Prenatal Diagnosis of COL4A1 Mutations in Eight Cases: Further Delineation of the Neurohistopathological Phenotype.

BACKGROUND: Increasing number of mutations responsible for vascular lesions, leading to ischemic or hemorrhagic stroke in young adults, has been identified in the recent years. It has been demonstrated in both mice and humans, that mutations in COL4A1 gene promote cerebral hemorrhages. In humans, both adults and children may be affected, and the spectrum has been broadened recently to neonates and fetuses. METHODS: We present a cohort of eight COL4A1 mutated fetuses in which cerebral hemorrhages were detected by ultrasound leading to elective terminations of pregnancy. RESULTS: Our neuropathological studies demonstrated a strikingly similar pathological pattern, dominated by supra- and infratentorial multifocal hemorrhagic lesions of various abundance and age in the vicinity of enlarged small vessels having a discontinuous wall. This was constantly associated with a spectrum of supratentorial post-ischemic damages of the grey and white matters. Morphometric studies of brain vessels confirmed vascular dilation and hypervascularization in both grey and white matters and severe attenuation of the smooth-muscle actin staining in the white matter. CONCLUSION: These observations add to the rare human neuropathological phenotype of COL4A1 mutations. Its recognition is mandatory to enhance the number of tested patients in the future, as well as the genetic counseling of parents.

Early prenatal diagnosis of alveolar capillary dysplasia with misalignment of pulmonary veins due to a 16q24.1 deletion.

First trimester ultrasound screening is an essential fetal examination performed generally at 11-13 weeks of gestation (WG). However, it does not allow for an accurate description of all fetal organs, partly due to their development in progress. Meanwhile, increased nuchal translucency (INT) is a widely used marker known to be associated with chromosomal deleterious rearrangements. We report on a 14 WG fetus with an association of INT and univentricular congenital heart malformation (CHM) leading to chorionic villous sampling (CVS). Cytogenetic investigations performed using array-Comparative Genomic Hybridization (CGH) and fluorescence in situ hybridization (FISH) demonstrated a 1.17 Mb deletion in 16q24.1 encompassing FOXF1 arisen de novo on maternal inherited chromosome. Fetopathological study confirmed CHM with hypoplastic left heart syndrome (HLHS) associating aortic atresia, mitral stenosis, and left ventricular hypoplasia and revealed in addition specific lung lesions corresponding to alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV). This is so far the first case of first trimester prenatal diagnosis of ACDMPV due to the deletion of FOXF1 gene. An interpretation of the complex genomic data generated by ultrasound markers is facilitated considerably by the genotype-phenotype correlations on fetopathological examination.

Fetal weight estimation: comparison of two-dimensional US and MR imaging assessments.

PURPOSE: To prospectively define fetal density in the second half of pregnancy by using magnetic resonance (MR) imaging and to compare estimates of fetal weight based on ultrasonography (US) and MR imaging with actual birth weight. MATERIALS AND METHODS: Written informed consent was obtained for this ethics committee-approved study. In this cross-sectional study between March 2011 and May 2012, fetal density was calculated as actual birth weight at delivery divided by fetal body volume at MR imaging in 188 fetuses between 20 weeks and 2 days and 42 weeks and 1 day of gestational age. Regression analysis was used to investigate the effect of variables, including sex, on fetal density. The US estimate of fetal weight was performed according to Hadlock et al, and the MR estimate of fetal weight was calculated based on the equation developed by Baker et al. US and MR estimates of fetal weight were compared with actual birth weights by using regression analysis. RESULTS: Median fetal density was equal to 1.04 (range, 0.95-1.18). Fetal density was significantly associated with gestational age at delivery but not with fetal sex. In 26.6% of fetuses, the US estimate of fetal weight had a relative error of more than 10%, while a similar relative error for the MR estimate of fetal weight occurred in only 1.1% of fetuses. The limits of agreement were narrower with the MR estimate of fetal weight compared with the US estimate of fetal weight. CONCLUSION: In the second half of pregnancy, fetal density varies with gestational age. Fetal weight estimates by using fetal MR imaging are better than those by using prenatal US.