Syndromic craniosynostoses related to FGFR genes: clinical and molecular study

Abstract

Syndromic craniosynostosis (SC) is characterized by the premature fusion of cranial sutures with extracranial anomalies and is associated with pathogenic variants in the genes encoding Fibroblast Growth Factor Receptors (FGFRs). In low-income countries, there are few studies on the genotype- phenotype correlation in patients with SC, which limits diagnosis and genetic counseling.

Objective: To describe a series of cases of syndromic craniosynostosis related to FGFR genes, with molecular confirmation.

Patients and Method: Descriptive case series conducted at the Genetics Institute of the Universidad Mayor de San Andrés, with patients diagnosed between 2017 and 2020. Demographic data, clinical findings, and syndromic diagnosis were recorded. Specific exons of FGFR1, FGFR2, and FGFR3 were sequenced in DNA extracted from peripheral blood using the Sanger technique.

Results: Nine patients were included: five with Apert syndrome, two with Crouzon syndrome, one with Pfeiffer syndrome, and one with Muenke syndrome. The median age was 3 years, with a male-to-female ratio of 7:2. Pathogenic variants were identified in FGFR2 in seven cases and in FGFR3 in one case, all consistent with the clinical diagnosis. One patient with a Pfeiffer phenotype was unable to complete the genetic study but met the clinical criteria for this condition.

Conclusions: We present a case series of Crouzon syndrome (CS), with clinically delineated and molecularly confirmed diagnosis. The clinical characteristics were consistent with the genetic findings, highlighting the importance of applying evaluation protocols in patients with CS. This strengthened the diagnostic capabilities of the research center and provided a confirmatory diagnosis to guide management and genetic counseling.