Novel variant in FGFR2 in a family with anterior segment anomalies.

BACKGROUND Ocular anomalies reported in FGFR2-related craniosynostosis include refractive errors, exophthalmos, and strabismus. Anterior segment anomalies have occasionally been reported in cases of FGFR2-related craniosynostosis.

METHODS We report a three-year-old boy with unilateral Peters anomaly, short stature, facial dysmorphism, posterior plagiocephaly, heart defects, and developmental delay. His maternal half-sister had bilateral posterior embryotoxon, dysmorphism, brittle teeth, umbilical hernia, developmental delay, heart defects, and microcephaly. Their mother had a normal slit lamp exam.

RESULTS A novel variant was found in FGFR2 (NM_000141.4: c.1376T>G p.(Met459Arg)) in the proband and maternal half-sister. No other variants of interest were identified in anterior segment genes. Incidentally, we identified a hemizygous variant in FGD1 (NM_004463.3: c.1292dupT p.(His432Profs*8)) in the proband; heterozygous in the mother.

CONCLUSION FGD1 is associated with Aarskog-Scott syndrome (AAS) while FGFR2 is linked with 14 different phenotypes. The proband's features suggest AAS except for Peters anomaly and heart defects, which have been reported with FGFR2 variants. The shared novel FGFR2 variant suggests a dual diagnosis for the proband. Our findings support a role for FGFR2 in anterior segment development and broaden the genotypic and phenotypic spectrum of FGFR2-related disorders.