Rapid detection of de novo P253R mutation in FGFR2 using uncultured amniocytes in a pregnancy affected by polyhydramnios, Blake's pouch cyst, and Apert syndrome

Objective: To present prenatal ultrasound and molecular genetic diagnosis of Apert syndrome.

Case report: A 30-year-old, gravida 3, para 2 woman was referred for genetic counseling at 32 weeks of gestation because of polyhydramnios and craniofacial and digital abnormalities in the fetus. She had undergone amniocentesis at 18 weeks of gestation because of maternal anxiety. Results of amniocentesis revealed a karyotype of 46,XX. A prenatal ultrasound at 32 weeks of gestation revealed a female fetus with a fetal biometry equivalent to 32 weeks, polyhydramnios with an increased amniotic fluid index of 26.1 cm, frontal bossing, midface hypoplasia, hypertelorism, Blake's pouch cyst with an apparent posterior fossa cyst in communication with the fourth ventricle on axial images, digital fusion, and bilateral syndactyly of the hands and feet. A DNA testing for the FGFR2 gene was immediately performed using uncultured amniocytes obtained by repeated amniocentesis, which revealed a heterozygous c.758C>G, CCT>CGT transversion leading to a p.Pro253Arg (P253R) mutation in the FGFR2 gene. Subsequently, a diagnosis of Apert syndrome was made. Molecular analysis of the FGFR2 gene in the parents did not reveal such a mutation. The fetus postnatally manifested frontal bossing, midface hypoplasia, and bilateral syndactyly of the hands (mitten hands) and feet.

Conclusion: Prenatal diagnosis of polyhydramnios, frontal bossing, and midface hypoplasia associated with brain and digital abnormalities should include a differential diagnosis of Apert syndrome. A molecular analysis of FGFR2 using uncultured amniocytes is useful for rapid confirmation of Apert syndrome at prenatal diagnosis.