Relationship between prenatal ultrasound signs and genetic abnormalities for fetal malformations of cortical development

Abstract

Purpose

To explore the relationship between ultrasound signs of suspected fetal malformation of cortical development (MCD) and genetic MCD.

Materials and Methods

The retrospective study involved fetuses with one of the following 10 neurosonography (NSG) signs: (A) abnormal development of the Sylvian fissure; (B) delayed achievement of cortical milestones; (C) premature or aberrant appearance of sulcation; (D) irregular border of the ventricular wall or irregular shape of the ventricle; (E) abnormal shape or orientation of the sulci; (F) hemispheric asymmetry; (G) non-continuous cerebral cortex; (H) intraparenchymal echogenic nodules; (I) persistent ganglionic eminence (GE) or GE cavitation; (J) abnormal cortical lamination.

Results

95 fetuses were included in the study. Chromosomal microarray (CMA) combined with exome sequencing (ES) was available in 40 fetuses, CMA was abnormal in nine and ES in 22. Sign C (7/7, 100%), sign H (2/2, 100%), sign A (18/19, 94.7%), and sign B (12/13, 92.3%) were the signs leading to the highest probability of genetic MCD. The incidence of genetic MCD for sign E, sign I, and sign D was 66.7–73.7%. Only one or none of the fetuses with sign J, sign F, or sign G underwent CMA+ES. The signs in the fetuses with FGFR3, CCND2, FLNA, or TSC2 mutations had the expected features. The other fetuses with different gene mutations showed several non-specific NSG signs.

Conclusion

Several reliable signs for genetic MCD can be detected by NSG, and the probability varies with different signs. Most signs are not associated with a specific gene. Therefore, CMA combined with ES is preferred.

Zusammenfassung

Ziel

Untersuchung des Zusammenhangs zwischen den Ultraschallzeichen bei Verdacht auf eine fetale Fehlbildung der kortikalen Entwicklung (MCD) und einer genetischen MCD.

Material und Methode

Die retrospektive Studie umfasste Föten mit einem der folgenden 10 neurosonografischen Zeichen und Merkmalen (NSG): (A) abnorme Entwicklung der Sylvischen Fissur; (B) verzögertes Erreichen der kortikalen Entwicklungsstadien; (C) verfrühtes oder abweichendes Auftreten der Sulkation; (D) unregelmäßiger Rand der Ventrikelwand oder unregelmäßige Form des Ventrikels; (E) abnorme Form oder Ausrichtung der Sulci; (F) hemisphärische Asymmetrie; (G) nicht kontinuierliche Großhirnrinde; (H) intraparenchymale echogene Knötchen; (I) persistierende ganglionäre Eminenz (GE) oder GE-Kavitation; (J) abnorme kortikale Laminierung.

Ergebnisse

95 Föten wurden in die Studie inkludiert. Chromosomen-Mikroarray (CMA), kombiniert mit Exom-Sequenzierung (ES), war bei 40 Föten verfügbar, CMA war bei 9 und ES bei 22 abnormal. Merkmal C (7/7, 100%), H (2/2, 100%), A (18/19, 94,7%) und B (12/13, 92,3%) waren die Veränderungen mit der höchsten Wahrscheinlichkeit für eine genetische MCD. Die Inzidenz der genetischen MCD für die Zeichen E, I und D lag bei 66,7–73,7%. Nur bei einem oder keinem der Föten mit Merkmal J, F oder G wurde eine CMA+ES durchgeführt. Die meisten Föten mit verschiedenen Genmutationen zeigten verschiedene unspezifische NSG-Zeichen.

Schlussfolgerung

Mit dem NSG können mehrere zuverlässige Zeichen für eine genetische MCD festgestellt werden. Die meisten Zeichen sind nicht mit einem bestimmten Gen verbunden. Daher ist die CMA in Kombination mit ES vorzuziehen.

Keywords

malformations of cortical development - neurosonography - chromosomal microarray - exome sequencing - prenatal ultrasound

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