[Clinical features and FGFR3 mutations of children with achondroplasia]

Area of Science:

• Pediatric genetics
• Skeletal dysplasias
• Molecular biology

Background:

• Achondroplasia (ACH) is a common skeletal dysplasia characterized by disproportionate short stature.
• Fibroblast growth factor receptor 3 (FGFR3) gene mutations are the primary cause of ACH.
• Understanding the spectrum of FGFR3 mutations and associated clinical features is crucial for diagnosis and management.

Purpose of the Study:

• To investigate the clinical manifestations and FGFR3 gene mutations in a cohort of 17 children with achondroplasia.
• To identify novel or uncommon FGFR3 gene mutations in pediatric ACH cases.
• To correlate genotype with phenotype in achondroplasia.

Main Methods:

• Retrospective analysis of clinical data from 17 children diagnosed with ACH between January 2009 and October 2021.
• Genetic analysis to detect mutations in the FGFR3 gene.
• Review of clinical and imaging findings, including skeletal dysplasia and complications.

Main Results:

• Common features included disproportionate short stature, macrocephaly, trident hands, and genu varum.
• Frequent complications observed were skeletal dysplasia, middle ear dysfunction, developmental delays, chronic pain, and sleep apnea.
• All 17 patients harbored FGFR3 mutations, with 13 showing the common c.1138G>A hotspot mutation. Two unreported mutations (c.1252C>T and c.445+2_445+5delTAGG) were identified.

Conclusions:

• The study identified previously unreported FGFR3 gene mutation sites, broadening the known mutation spectrum for achondroplasia.
• Achondroplasia is a progressive condition necessitating long-term, multidisciplinary care.
• Genetic characterization aids in understanding ACH and potentially guiding future therapeutic strategies.