Prenatal Diagnosis of Pfeiffer Syndrome Patient with FGFR2 C.940-1G>C Variant: A Case Report

Abstract

Background: Pfeiffer syndrome (PS) is an autosomal dominant disorder caused by mutations in fibroblast growth factor receptor FGFR1 and FGFR2 genes, occurring in approximately 1:100,000 live births. PS has a wide range of clinical expression and severity, so early prenatal diagnosis is difficult and genetic counseling is desirable. We describe a PS newborn with her ultrasound and molecular studies.

Case report: We describe a female term newborn with cloverleaf-shaped skull, facial hypoplasia, low ears, exophthalmos and wide, broad and deviated thumbs and hallux. The patient was diagnosed by ultrasound at 29 WGA and referred to a tertiary care hospital for her follow-up. Molecular test revealed a heterozygous pathogenic variant in intron 8 of the FGFR2 gene (FGFR2: c.940-1G>C). It was a de-novo mutation. At 17 days of life, craniosynostosis correction and a Lefort-III frontomaxillary advancement were performed.

Conclusion: Pfeiffer syndrome is a devastating genetic disorder. Prenatal diagnosis according PS morphological features in prenatal ultrasound allows timely genetic counseling, early referral to third-level centers, and close follow-up in the prenatal and postnatal stages.

Keywords: Pfeiffer syndrome; acrocephalosyndactylia; craniosynostosis; fibroblast growth factor receptor 2.

Figure 1

3D-ultrasound at 29 WGA. The foetus has frontal prominence and a cloverleaf skull suggestive of craniosynostosis and hypoplastic nasal bone (white arrows).

Figure 2

Physical findings at birth. (A and B). Female newborn with cloverleaf skull, hypertelorism, facial hypoplasia, low ears, exophthalmos, (C) short and deviated hallux and (D) thumbs.