Abstract
Prenatal detection of recurrent structural anomalies presents complex challenges in
fetal prognosis and genetic counseling. We report the case of a 25-year-old woman
with three consecutive pregnancies affected by bilateral hyperechoic, enlarged fetal
kidneys and associated anomalies. In the first pregnancy, anomaly scan at 18 + 6 weeks
revealed enlarged hyperechoic kidneys, Dandy-Walker malformation, and echogenic bowel.
The pregnancy was terminated; microarray analysis was normal. A year later, her second
pregnancy showed similar renal findings along with enlarged lateral ventricles, absent
cavum septum pellucidum, and microcephaly. Trio whole-exome sequencing identified
compound heterozygous variants in the CPT2 gene in the fetus: c.28_29insAGCAAG and
c.1891C > T. Both parents were found to be heterozygous carriers. In the third pregnancy,
clinical exome sequencing was offered as prenatal testing despite a normal ultrasound.
The fetus was initially reported as “affected” with the same compound heterozygous
CPT2 variants. However, reanalysis by a clinical geneticist revealed that both variants
were in cis configuration in the parents and fetus, indicating a carrier status rather
than disease. This case underscores the importance of detailed variant interpretation,
phase determination, and expert genetic counseling in managing suspected fetal CPT2
deficiency, especially in cases presenting with recurrent antenatal anomalies.
Keywords
CPT2 gene - fetal renal anomalies - prenatal diagnosis - compound heterozygosity -
genetic counseling
