Abstract

Congenital brain malformations constitute a serious problem for public health. Occurring in 2 to 3 cases per 1000 pregnancies, they represent one of the most frequent causes of therapeutic termination of pregnancies. At birth, they represent a major cause of various forms of intellectual disabilities. The quality of life of affected children, adults, and their families is seriously impacted. While Ultrasound remains the standard gold of fetal malformation screening, Magnetic Resonance Imaging (MRI) has recently been a useful complementary method for detecting brain malformations. During genetic counseling, accurate morphological diagnosis is essential to promote genetic diagnosis and molecular targeting and consequently better management of subsequent pregnancies by estimating the recurrence rate. We aimed through this study to analyze the utility of post-mortem MRI for brain malformations during fetal autopsy in terms of its contribution to establishing an accurate genetic diagnosis and its impact on genetic counseling. In a retrospective study spanning 4 years, we reviewed our genetic counseling reports of couples with terminated singleton pregnancies. We reviewed prenatal ultrasound and post-mortem pathology and morphology reports. We considered the cases with congenital brain malformations. Written informed consent was obtained from all parents for post-mortem morphologic and genetic examinations. Our study revealed ten couples with terminated singleton pregnancies because of the discovery of congenital brain malformations on prenatal ultrasound. In all cases, fetal autopsy was carried out with histo-pathological examinations. Post-mortem radiography and MRI explorations were accomplished in four cases leading to an accurate medical genetic diagnosis (which must be confirmed by NGS). The average fetus's age was 26 SA. Post-mortem brain MRI showed more precisely posterior fossa cysts detected on ultrasound as a Blake's pouch in case 1, revealed gigantic cerebral calcifications that were not visible on ultrasound (confirmed after MRI by scanner imaging) in case 2, specified the extent of a ventriculomegaly suspected on ultrasound in case 3 and identified a corpus callosum abnormality associated to ocular malformations in the fourth case. Because of significant genotypic and phenotypic heterogeneity for most genetic syndromic entities as well as for genetic developmental disorders associated with congenital brain malformations, a comprehensive analysis of clinical, imaging, histo-pathological, and medical genetic data is needed to orientate properly post-mortem genetic testing in terminated pregnancies. In addition to post-mortem brain MRI, prenatal MRI seems to be more sensitive and accurate than ultrasound in diagnosing fetal brain abnormalities and should be performed when there is an ultrasound of fetal brain abnormalities. On the other hand, in the absence of ultrasound brain suspected images, brain prenatal MRI may be indicated to study associated brain abnormalities to other congenital malformations visible at ultrasound.