FGFR2 – Saethre-Chotzen syndrome

FGFR2 is implicated in a subset of autosomal dominant cases of Saethre-Chotzen syndrome, a craniosynostosis disorder characterized by brachycephaly, facial asymmetry, ptosis, hypertelorism, clinodactyly, broad hallux, and low anterior hairline. In a cohort of 32 unrelated SCT patients, one individual harbored a heterozygous in-frame deletion c.804_809delAGTGGT (p.Val269_Val270del) in FGFR2 ([PMID:9585583])—indicating genetic heterogeneity alongside the more common TWIST1 and FGFR3 mutations.

Genetic evidence for FGFR2 in SCT remains limited: only 1 proband and no confirmed segregation or additional variants have been reported, and no functional assays have directly assessed this deletion in SCT. The current evidence supports a Limited ClinGen classification of the FGFR2–Saethre-Chotzen association. The distinct FGFR2 variant expands the mutational spectrum but requires further familial studies and functional validation. Key Take-home: FGFR2 variants can underlie rare autosomal dominant SCT cases, warranting inclusion in diagnostic panels despite limited validation.

References

• American journal of human genetics • 1998 • Genetic heterogeneity of Saethre-Chotzen syndrome, due to TWIST and FGFR mutations. PMID:9585583

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