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Q289P mutation in the FGFR2 gene: first report in a patient with type 1 Pfeiffer syndrome
Maria Piccione1, Vincenzo Antona, Marcello Niceta
1Dipartimento Materno Infantile, Università di Palermo, via Cardinale Rampolla 1, Palermo 90142, Italy. piccionemaria@libero.it
Insights
Craniosynostosis, a premature fusion of skull bones, can result from disrupted calvarial suture development. A novel FGFR2 gene mutation in Pfeiffer syndrome suggests these conditions may be a single genetic disorder with varied presentations.
Area of Science:
- Genetics
- Developmental Biology
- Molecular Biology
Background:
- Craniosynostosis involves premature fusion of calvarial sutures, leading to abnormal head shape, midface hypoplasia, and ocular abnormalities.
- Classical craniosynostosis syndromes, including Apert, Pfeiffer, Crouzon, Jackson-Weiss, and Saethre-Chotzen, are autosomal dominant and linked to mutations in fibroblast growth factor receptors (FGFRs).
Observation:
- This study reports a child diagnosed with Pfeiffer syndrome exhibiting a missense point mutation, Q289P, in exon 8 of the FGFR2 gene.
- This specific FGFR2 mutation has not been previously associated with Pfeiffer syndrome but has been documented in Crouzon, Jackson-Weiss, and Saethre-Chotzen syndromes.
Findings:
- The identified Q289P mutation in the FGFR2 gene in a Pfeiffer syndrome patient expands the known mutational spectrum for this condition.
- The presence of a mutation typically seen in other craniosynostosis syndromes within a Pfeiffer syndrome case challenges distinct diagnostic boundaries.
Implications:
- These findings suggest that classical craniosynostosis syndromes might represent a spectrum of a single genetic condition with significant phenotypic variability.
- Further research into FGFR2 mutations and their phenotypic correlations is warranted to understand the underlying mechanisms of craniosynostosis and refine diagnostic approaches.
Abstract:
When normal development and growth of the calvarial sutures is disrupted, craniosynostosis (premature calvarial suture fusion) may result. Classical craniosynostosis syndromes are autosomal dominant traits and include Apert, Pfeiffer, Crouzon, Jackson-Weiss, and Saethre-Chotzen syndromes. In these conditions, there is premature fusion of skull bones leading to an abnormal head shape, ocular hypertelorism with proptosis, and midface hypoplasia. It is known that mutations in the fibroblast growth factor receptors 1, 2, and 3 cause craniosynostosis. We report on a child with a clinically diagnosed Pfeiffer syndrome that shows the missense point mutation Q289P in exon 8 of the FGFR2 gene. This is a mutation not previously described in the Pfeiffer syndrome but reported in the Crouzon, Jackson-Weiss, and Saethre-Chotzen syndromes. In this paper, we propose the concept that these disorders may represent one genetic condition with phenotypic variability.
