Carnitine palmitoyltransferase II (CPT2) deficiency is a rare inborn error of mitochondrial fatty acid metabolism associated with various phenotypes. Whereas most patients present with postnatal signs of energetic failure affecting muscle and liver, a small subset of patients presents antenatal malformations including brain dysgenesis and neuronal migration defects. Here, we report recurrence of severe cerebral dysgenesis with Dandy-Walker malformation in three successive pregnancies and review previously reported antenatal cases. Interestingly, we also report that acylcarnitines profile, tested retrospectively on the amniotic fluid of last pregnancy, was not sensitive enough to allow reliable prenatal diagnosis of CPT2 deficiency. Finally, because fetuses affected by severe cerebral malformations are frequently aborted, CPT2 deficiency may be underestimated and fatty acid oxidation disorders should be considered when faced with a fetus with Dandy-Walker anomaly or another brain dysgenesis.

We compared the diagnostic yield of fetal clinical exome sequencing (fCES) in prospective and retrospective cohorts of pregnancies presenting with anomalies detected using ultrasound. We evaluated factors that led to a higher diagnostic efficiency, such as phenotypic category, clinical characterization, and variant analysis strategy. Methods: fCES was performed for 303 fetuses (183 ongoing and 120 ended pregnancies, in which chromosomal abnormalities had been excluded) using a trio/duo-based approach and a multistep variant analysis strategy. Results: fCES identified the underlying genetic cause in 13% (24/183) of prospective and 29% (35/120) of retrospective cases. In both cohorts, recessive heterozygous compound genotypes were not rare, and trio and simplex variant analysis strategies were complementary to achieve the highest possible diagnostic rate. Limited prenatal phenotypic information led to interpretation challenges. In 2 prospective cases, in-depth analysis allowed expansion of the spectrum of prenatal presentations for genetic syndromes associated with the SLC17A5 and CHAMP1 genes. Conclusion: fCES is diagnostically efficient in fetuses presenting with cerebral, skeletal, urinary, or multiple anomalies. The comparison between the 2 cohorts highlights the importance of providing detailed phenotypic information for better interpretation and prenatal reporting of genetic variants.

A 45‐year‐old woman underwent serial ultrasound screening procedures during late first and second trimesters of pregnancy for advanced maternal age. Cultured amniocytes karyotype indicated full trisomy 21. Subsequently, the fetus developed congenital cataract diagnosed at 24 weeks. This is the first antenatal diagnosis of this complication of Down syndrome. Copyright © 1999 John Wiley & Sons, Ltd.

We present a case of de novo trisomy of distal 19q diagnosed prenatally by cytogenetics and FISH analysis. The autopsy performed after termination of the pregnancy showed major internal and external malformations that are associated with this chromosome abnormality.

We report on a fetus with multiple congenital anomalies detected at the prenatal ultrasound examination and a trisomy 6 mosaicism in the amniocytes. The pregnancy was interrupted in the 18th gestational week and the autopsy revealed malformations including cleft right hand, arthrogryposis and hypoplasia of the 4th digit of the left hand, syndactylies and overlapping toes, facial dysmorphism with hypertelorism and low-set ears, ventricular septum defect (VSD), intestinal malrotation and scoliosis. Trisomy 6 mosaicism was detected in cultured amniocytes (13.3%), confirmed in umbilical cord fibroblasts (40%) and by fluorescence in situ hybridization on other fetal tissues. Trisomy 6 mosaicism is a very rare finding with only eight cases previously reported to our best knowledge.