A postzygotic variant in FGFR2 has been identified as the cause of a mosaic neurocutaneous disorder. Researchers at the Institute of Human Genetics Göttingen uncovered the variant as the disease-causing genetic defect in a patient with skin anomalies (nevi), eye malformations, macrocephaly and mild developmental delay and they showed in functional analyses that the variant results in constitutive activation of the encoded receptor protein. Clinically, the girl had been diagnosed with a suspected Schimmelpenning-Feuerstein-Mims syndrome. Exome sequencing on DNA from blood and from affected skin tissue revealed the variant in FGFR2, allowing the molecular diagnosis. FGFR2 should thus be considered in the molecular diagnostics in patients with a suspected mosaic neurocutaneous disorder.

FGFR2 is a member of the family of fibroblast growth factor receptors. These proteins bind fibroblast growth factors, triggering various downstream intracellular signaling cascades including the Ras/Raf/MAPK and the PI3K-Akt signaling pathways. FGFRs are thus centrally involved in many fundamental cellular processes. FGFR2 plays an important role in embryonic development and also in the adult organism, for example in tumorgenesis and angiogenesis. Heterozygous germline variants in FGFR2 have been described as causing various autosomal dominantly inherited syndromes associated with craniosynostosis (premature closing of sutures) and skeletal malformations.

The results of the study were published in Human Genetics.