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Brain malformations, particularly related to early brain development, are a clinically and genetically heterogeneous group of fetal neurological disorders. Fetal cerebral malformation, predominantly of impaired prosencephalic development namely agenesis of the corpus callosum and septo-optic dysplasia, is the main pathological feature in fetus, and causes prominent neurodevelopmental retardation, and associated with congenital facial anomalies and visual disorders. Differential diagnosis of brain malformations can be extremely difficult even through magnetic resonance imaging. Advances in genomic and molecular genetics technologies have led to the identification of the sonic hedgehog pathways and genes critical to the normal brain development. Molecular cytogenetic and genetic studies have identified numeric and structural chromosomal abnormalities as well as mutations in genes important for the etiology of fetal neurological disorders. In this review, we update the molecular genetics findings of three common fetal neurological abnormalities, holoprosencephaly, lissencephaly and agenesis of the corpus callosum, in an attempt to assist in perinatal and prenatal diagnosis., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Advanced transvaginal neurosonography has revealed normal and abnormal intracranial morphology. Transvaginal three-dimensional (3D) sonography demonstrates bony structure, multiplanar analysis of inside detailed morphology, tomographic ultrasound imaging in any cutting sections, 3D sonoangiography and volume calculation of ventricles and/or intracranial lesions. Longitudinal assessment of normal and abnormal central nervous system (CNS) development is done by serial scanning. However, the transvaginal high-frequency approach has several limitations due to lack of penetration and cranial bone ossification with advanced gestational age. Magnetic resonance neuroimaging enabled observation of the whole intracranial cavity, brainstem and cortical gyral/sulcal development. On the other hand, neuro-sonography has advantages in detecting intracranial calcification, vascular abnormalities, intratumoral vascularity and bone dysplasia. Moreover, 3D ultrasound demonstrates extra CNS abnormalities, strongly associated with CNS abnormalities. Any less-invasive modalities can be used for a CNS anomaly screening scan and ultrasound is no doubt the first choice. Once CNS abnormality is suspected, it is suggested to use the different technologies according to what is looked for in each abnormal CNS case. Of course, MR and 3D ultrasound imaging should be complementary as well as alternative.

Summary: Fetal imaging technology has been advancing remarkably and prenatal detection and diagnoses have been moved forward from the second and third trimesters to the first trimester. Structural abnormalities detected by fetal imaging often lead to prenatal diagnoses of genetic disorders. However, there are still dilemmas in fetal diagnoses in normal karyotype cases with strong suspicion of congenital genetic disorders from sonographic findings. When fetal sonography reveals multiple minor abnormalities originating from various organs, counseling dilemmas and parental anxieties become greater than before karyotyping. Array-comparative genomic hybridization (aCGH) was developed as a high-resolution analysis of DNA copy number variations (CNVs). In seven cases presenting with abnormal brain structures by fetal imaging, abnormal CNVs were confirmed by aCGH but conventional karyotyping yielded normal results. Although careful patient selection is required in order to deal with microarray results and parental counseling, ‘sonogenetics’ – incorporating the idea of ‘fetuses first’ – will play an important role in the era of molecular genetics. Recent advances in non-invasive prenatal testing by using fetal cell-free DNA in maternal plasma has the potential to generate misleading prenatal diagnoses without the observation of fetuses. However, no fetal diagnoses should be made without observing fetuses and we must not forget ‘the fetus as a patient’. [Copyright &y& Elsevier]

Summary: Fetal brain is rapidly developing and changing its appearance week by week during pregnancy. It is quite difficult to observe detailed structure of the brain by conventional transabdominal sonography. Transvaginal high-resolution ultrasound and three-dimensional (3D) ultrasound have been establishing sonoembryology in the first trimester as well as neurosonography. It is possible to observe the whole brain structure by magnetic resonance imaging in the latter half of pregnancy but transvaginal high-resolution 3D ultrasound is also a powerful modality for understanding brain anatomy. As for brain vascularization, main arteries and veins have been demonstrated and evaluated in various central nervous system conditions. Transvaginal high-resolution 3D ultrasound can demonstrate even cerebral fine vascular anatomy such as medullary vessels and it is greatly expected to estimate neurological prognosis in relation to vascular development during the fetal period. [ABSTRACT FROM AUTHOR]

Summary: High-resolution three-dimensional (3D) ultrasound has enabled the visualization of small embryos and fetuses, and embryology in vivo – ‘3D sonoembryology’ – has been established based on conventional embryology. Recently developed imaging techniques allow the definition of in-vivo anatomy including visualization of the embryonic circulation and dynamic features that could not be characterized in fixed specimens. Three-dimensional ultrasound has facilitated increasingly accurate and objective prenatal diagnoses of cranium bifidum/spina bifida, holoprosencephaly and associated anomalies in the first trimester and may allow detection of pathologic central nervous system (CNS) development at an earlier gestational age. It may be no exaggeration to suggest that prenatal diagnoses of fetal abnormalities have shifted from second to first trimester. However, fetal brain develops rapidly in the second trimester, therefore early scanning covers only selected CNS anomalies described in this article and serial continuous observation in the second trimester will be required. [ABSTRACT FROM AUTHOR]

Aims: This study examined whether analysis of fetal behavioral states by monitoring fetal heart rate and movement using an actocardiogram (ACG), could provide prognostic information related to fetal central nervous system (CNS) lesions. Methods: The ACG simultaneously records fetal heart rate (FHR) and fetal movement bursts composed of spikes of ultrasonic Doppler signals. Durations of FHR accelerations and fetal movement bursts were measured manually. Five actocardiographic indices were studied in 12 fetuses with CNS lesions and in 14 normal pregnancies of 28–38 weeks. Results: Severity of the fetal CNS lesions was estimated from the acceleration/burst (A/B) duration ratio, which correlated with the rank of the sonographic fetal functional test in cases with CNS lesions. Severity of a fetal lesion may also be estimated by the regression equation of the A/B duration ratio and behavioral ranking. Conclusion: The severity of fetal CNS lesions may be estimated by quantitative analysis of ACG usings the measurement of A/B duration ratio to provide a prognosis. An ACG may demonstrate a loss of CNS control in cases with severe brain damage. [ABSTRACT FROM AUTHOR]