Advanced genomic testing may aid in counseling of isolated agenesis of the corpus callosum on prenatal ultrasound. (3rd December 2017)

• Record Type: Journal Article
• Authors: de Wit, M.C.; Boekhorst, F.; Mancini, G.M.; Smit, L.S.; Groenenberg, I.A.L.; Dudink, J.; de Vries, F.A.T.; Go, A.T.J.I.; Galjaard, R.J.H.
• Is Part Of: Prenatal diagnosis. Volume 37:Number 12(2017)
• Page Start: 1191
• Page End: 1197
• Publication Date: 2017-12-03
• Subjects: Prenatal diagnosis -- Periodicals; Fetus -- Diseases -- Diagnosis -- Periodicals; Electronic journals; 618.32075
• DOI: 10.1002/pd.5158
• Languages: English
• ISSNs: 0197-3851

Abstract

Abstract: Objective: Isolated agenesis of the corpus callosum on fetal ultrasound has a varied prognosis. Microarray and exome sequencing (ES) might aid in prenatal counseling. Method: This study includes 25 fetuses with apparently isolated complete corpus callosum (cACC) on ultrasound. All cases were offered single nucleotide polymorphism array. Complementary ES was offered postnatally in selected cases. Clinical physical and neurodevelopmental follow‐up was collected. Results: Eighteen cases opted for single nucleotide polymorphism array testing, which detected a causal anomaly in 2/18 (11.1%; 95% CI 2.0%‐31%). Among ongoing pregnancies without a causal anomaly on microarray, 30% (95% CI 8.5%‐60%) showed intellectual disability. Postnatal magnetic resonance imaging and physical examination often (64%; 95% CI 38%‐85%, and 64%; 95% CI 38%‐85%, respectively) revealed additional physical anomalies in cases without a causal anomaly on microarray. Two cases appeared truly isolated after birth. Postnatal sequencing in 4 of 16 cases without a causal anomaly on microarray but with intellectual disability and/or additional postnatal physical anomalies revealed 2 single‐gene disorders. Therefore, the estimated diagnostic yield of ES in chromosomally normal cACC fetuses is between 2/4 (50%; 95% CI 11%‐89%) and 2/16 (13.3%; 95% CI 2.4%‐36%). Conclusion: In accordance with current guidelines, we conclude that microarray should be offered in case of isolated cACC on ultrasound. ES is likely to be informative for prenatal counseling and should be offered if microarray is normal. Abstract : What's already known about this topic? Agenesis of the corpus callosum is associated with a varied fetal prognosis. The presence of a genetic syndrome is an important determinant in the fetal prognosis. What does this study add? Single nucleotide polymorphism array and exome sequencing can be informative for prenatal counseling in fetuses with isolated complete ACC on prenatal ultrasound.