Fetal intracranial hemorrhage in second trimester: An ominous finding even after a normal array

Objective

This is a case report of a COL4A1 gene mutation which was confirmed by further genetic testing following anomalies observed in prenatal ultrasound and fetal brain magnetic resonance imaging (MRI).

Case reports

The ultrasound examination of the patient revealed a mass in fetal left intracranial cavity. Repeated subsequent MRI detected an evolving mass in the left frontal parietal lobe. All tests such as karyotyping, chromosomal microarray analysis (CMA), and PCR-cytomegalovirus detection of amniotic fluid, returned negative results. However, the whole exome sequencing (WES) identified a heterozygous missense mutation that was considered pathogenic in the COL4A1 (NM_001844.6) gene: c.3715G > A (p.Gly1239Arg). Consequently, the couple chose to terminate the pregnancy and refused the pathological examination of the fetus.

Conclusion

This case underscores the importance of image-assisted examinations such as prenatal ultrasound and MRI, and that WES is a critical tool to establish the genetic etiology.