FGFR2 Genetic Variant C.1019A > G p.(Tyr340Cys) in a Fetus with Pfeiffer Type II Syndrome Diagnosed by a Combination of 3D Ultrasound Phenotyping and DNA Sequencing

Abstract

A 38-year-old woman was referred at 20 weeks' gestation for multiple fetal anomalies detected on routine ultrasound screening. Initial findings included dolichocephaly, ventriculomegaly, craniofacial abnormalities, and limb anomalies, which led to the suspicion of a skeletal dysplasia. While microarray analysis was normal, rapid fetal exome sequencing identified a de novo pathogenic variant in the FGFR2 gene (c.1019A > G p.(Tyr340Cys)). Initially classified as a variant of uncertain significance due to initial ultrasound suspicion, targeted three and four dimensional ultrasound phenotyping revealed characteristic features of Pfeiffer syndrome type 2, including cloverleaf skull, proptosis, hypertelorism, broad thumbs and big toes, and radial-humeral synostosis. This case demonstrates the crucial interplay between advanced genetic testing and detailed ultrasound assessment in prenatal diagnosis. Accurate interpretation of genetic variants requires meticulous ultrasound phenotyping in a multidisciplinary setting, particularly for complex and rare conditions such as Pfeiffer syndrome type 2.

Keywords

Pfeiffer type II syndrome - prenatal phenotyping - prenatal exome sequencing - FGFR2 gene variant c.1019A > G p.(Tyr340Cys) - three-dimensional ultrasound

Consent to Publish Statement

Written informed consent was obtained from the mother for the publication of potentially identifying images and clinical details.

Authors' Contributions

Conceptualization: S.M.S., C.J.M., and L.C.C. Methodology: S.M.S. and C.J.M. Case management: H.N.L., C.S.A., and T.D. Informed consent: T.D. Writing—original draft preparation: S.M.S. and C.J.M. Writing—review and editing: L.C.C., H.N.L., C.S.A., and T.D. Supervision: L.C.C. and C.J.M. All authors have read and agreed to the published version of the manuscript.

Data Availability

The authors confirm that the data supporting the findings of this study are available only within the article.

Publikationsverlauf

Artikel online veröffentlicht:
01. Juli 2025

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