Shot CommunciationIncreased FGF3 and FGF4 gene dosage is a risk factor for craniosynostosis

- A patient with ID, postnatal microcephaly and craniosynostosis is described.
- Array-CGH analysis revealed a de novo 290 kb interstitial duplication of 11q13.3.
- The duplication encompasses the CCND1, ORAV1, FGF19, FGF3 and FGF4 genes.
- A minimal duplicated region associated with craniosynostosis was defined.
- Duplication of the FGF3 and FGF4 genes is a risk factor for craniosynostosis.

Interstitial duplications involving chromosome 11q have rarely been reported in the literature and mainly represent large, cytogenetically detectable rearrangements associated with a wide and variable spectrum of neurodevelopmental disorders. We report on a patient affected by intellectual disability, craniosynostosis, and microcephaly. Array-CGH analysis identified a de novo 290 kb interstitial duplication of chromosome 11q13.3 including the FGF3 and FGF4 genes. Clinical comparison of our patient with those previously reported with overlapping 11q duplications allows us to define the minimal duplicated region associated with craniosynostosis and strongly supports the hypothesis that the constitutional increased dosage of the FGF3 and FGF4 genes is a risk factor for craniosynostosis in humans.