Fetal Familial Cerebral Cavernous Malformation With a Novel Heterozygous Variation.

BACKGROUND AND OBJECTIVES

To identify fetal familial cerebral cavernous malformation (CCM) and a novel variation.

METHODS

A 37-year-old pregnant woman (G4P0) presented with right-handed numbness since 2 weeks at 31 weeks of gestation. Evaluation with brain MRI revealed multiple CCMs. As a result, fetal MRI, fetal whole exome sequencing, and maternal Sanger sequencing were performed.

RESULTS

The mother's brain MRI demonstrated numerous CCMs involving the brain stem, cerebral hemispheres, and cerebellum. Fetal MRI showed a CCM located in the left frontal lobe in susceptibility-weighted imaging (SWI). The neuroimaging characteristics of the mother and the fetus suggested that their CCMs may be familial. Genetic analysis revealed a novel variation in (c.1A>G, p.0?), also called , in the mother and the baby. The mother delivered a daughter at 32 weeks of gestation with an Apgar score of 10 by cesarean section.

DISCUSSION

This variation of the initial codon in the gene leads to a phenotype with an early-onset. To our knowledge, this is the first-ever reported case of fetal familial CCM and this novel variation. Brain MRI has excellent sensitivity and specificity, providing the best option for detecting CCMs, even in utero, primarily when SWI is used.