The Incidence of Chromosomal Aberrations in Prenatally Diagnosed Isolated Agenesis of the Corpus Callosum

Abstract

Purpose To establish the prevalence of chromosomal aberrations in fetuses with an apparently isolated agenesis of the corpus callosum (ACC) on prenatal ultrasound.

Materials & Methods This was a retrospective study of complete isolated ACC at the time of ultrasound evaluation with respect to karyotype information. Within this group, a subgroup with non-malformation minor abnormalities, such as a single umbilical artery (SUA), polyhydramnios or fetal growth restriction (FGR), was investigated.

Results Complete ACC was diagnosed in 343 cases. Of them, 143 (41.6 %) were isolated, with 16 fetuses showing additional minor findings. In 76.2 % (109/143) karyotyping was performed. Additional array CGH analysis was performed in 7.7 % (11/143). Chromosomal aberrations were found in 4.6 % (5/109) overall, in 3.1 % (3/98) of those without any additional sonographic findings (all represented mosaic trisomy 8) and in 18.2 % (2/11) of those with minor abnormalities. The prevalence of pathogenic submicroscopic copy number variant (CNV) was 9 % (1/11).

Conclusion Fetal karyotyping is recommended in ACC, as trisomy 8 mosaicism should be considered despite otherwise unremarkable ultrasound. The role of novel techniques such as array CGH and its implication has to be explored in prospective studies.

Zusammenfassung

Ziel Untersuchung der Prävalenz chromosomaler Aberrationen bei Feten mit pränatal sonographisch isolierter Agenesie des Corpus callosums (ACC).

Material und Methoden Retrospektive Analyse der Daten zur Karyotypisierung bei Feten mit Verdacht auf sonografisch isolierte komplette CCA. Als Untergruppe wurden die Daten von Feten mit milden (,minor’) Auffälligkeiten, wie singuläre Nabelschnurarterie, Polyhydramnion oder Wachstumsretardierung ausgewertet.

Ergebnisse Eine vollständige ACC wurde in 343 Fällen diagnostiziert. Hiervon waren 143 (41,6 %) isoliert, 16 dieser Feten zeigten milde Auffälligkeiten, jedoch keine Fehlbildungen. Informationen zum Karyotyp waren in 76,2 % (109/143) verfügbar. Eine zusätzliche Array CGH Analyse wurde in 7,7 % (11/143) durchgeführt. Insgesamt zeigten 4,6 % (5/109) der Feten chromosomale Auffälligkeiten, davon 3,1 % (3/98; alle mit Mosaik Trisomie 8) in der Gruppe der isolierten ACC und 18,2 % (2/11) in der Untergruppe mit „minor“ Anomalien. Die Prävalenz von pathogenen submikroskopischen Copy Number Variationen (CNV) lag bei 9 % (1/11).

Schlussfolgerungen Eine Karyotypisierung ist auch bei Verdacht auf sonografisch isolierte ACC empfohlen, da trotzdem eine Mosaik-Trisomie 8 vorliegen kann. Der Einsatz neuerer genetischer Methoden wie Array CGH und deren Wertigkeit muss in weiteren prospektiven Studien untersucht werden.

Key words

corpus callosum agenesis - prenatal diagnosis - ultrasonography - karyotype - prenatal Array CGH

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