First-trimester cystic hygroma and neurodevelopmental disorders: The association to remember

We present two prenatal cases of first-trimester cystic hygroma who are later found to suffer from rare genetic syndromes.

Both of the two pregnant women were showed to have fetal cystic hygroma on ultrasound at the first trimester. Fetal microarray result was normal. Follow-up sonographic examinations showed no structural anomalies. The two pregnancies continued uncomplicatedly to term. However, the two infants developed early neurodevelopmental syndrome within two years of age. Exome sequencing confirmed that one child had Mental retardation, autosomal dominant 23 (MRD23) with a c.646delC (p.Q216Sfs∗35) variant in SETD5 gene, and the other child had Smith-Magenis syndrome with a c.3103dupC (Q1035Pfs∗31) variant in RAI1 gene.

Clinicians have to be vigilant when counseling the patient whose fetus has a first-trimester cystic hygroma even with a normal array result and normal sonographic scans. Although they are rare, monogenetic syndromes are possible outcomes.