Prenatal diagnosis of Neu-Laxova syndrome with compound heterozygous variants in PHGDH in a fetus presenting increased nuchal translucency and severe early-onset fetal growth restriction in a dichorionic diamniotic twin pregnancy.

OBJECTIVE: We present prenatal diagnosis of Neu-Laxova syndrome with compound heterozygous variants in PHGDH in a fetus presenting increased nuchal translucency (NT) and severe early-onset fetal growth restriction (FGR) of a dichorionic diamniotic (DCDA) twin pregnancy.

CASE REPORT: A 36-year-old, gravida 3, para 1, woman with an adverse pregnancy history of fetus demise, now bearing a DCDA twin pregnancy conceived by IVF-ET, underwent amniocentesis at 17+2 weeks of gestation because of one of the twin presenting increased NT at 13 + 1 weeks of gestation, and karyotype, FISH and SNP revealed no genetic abnormity. Since 22 weeks of gestation, severe FGR was presented in ultrasound in the fetus with increased NT. Fetal ultrasonic cardiogram at 26 + 1 weeks of gestation reported no abnormity. Trio-WES prescribed at 29+4 weeks of gestation revealed compound heterozygous variants in the affected fetus in PHGDH (NM_006623.4): a known missense variant c.488G > A (p.Arg163Gln) (ClinVar; [VCV000139535.8]) inherited from the father and a novel missense variant c.1129G > C (p.Gly377Arg) inherited from the mother. Brain fetal MRI performed at 36 + 6 weeks of gestation showed callosal agenesis, meanwhile, fetal ultrasound at 36 + 6 weeks of gestation re-confirmed microcephaly and micrognathia in the affected fetus.

CONCLUSION: A novel likely pathological missense variant causing NLS: NM_006623.4(PHGDH):c.1129G > C (p.Gly377Arg) was reported. Trio WES shall be prescribed sequentially after a normal SNP result for fetus with early-onset severe FGR to rule out pathological genetic causes and provide guidance for future reproduction.