Craniofacial growth and function in achondroplasia: a multimodal 3D study on 15 patients

BackgroundAchondroplasia is the most frequent FGFR3-related chondrodysplasia, leading to rhizomelic dwarfism, craniofacial anomalies, stenosis of the foramen magnum, and sleep apnea. Craniofacial growth and its correlation with obstructive sleep apnea syndrome has not been assessed in achondroplasia. In this study, we provide a multimodal analysis of craniofacial growth and anatomo-functional correlations between craniofacial features and the severity of obstructive sleep apnea syndrome.Methods A multimodal study was performed based on a paediatric cohort of 15 achondroplasia patients, including clinical and sleep study data, 2D cephalometrics, and 3D geometric morphometry analyses.ResultsCraniofacial phenotype was characterized by maxillo-zygomatic retrusion, deep nasal root, and prominent forehead. 2D cephalometric studies showed constant maxillo-mandibular retrusion, with excessive vertical dimensions of the lower third of the face, and modifications of cranial base angles. All patients with available CT-scan had premature fusion of skull base synchondroses. 3D morphometric analyses showed an aggravation of the craniofacial phenotype with age, predominantly affecting the midface - with increasing maxillary retrusion with age - as well as the skull base - with closure of the spheno-occipital angle. At mandibular level, both mandibular corpus and ramus showed significant levels of shape modifications with age, the highest level concerned the mandibular corpus (+119%). Anatomo-functional studies revealed significant correlation between the severity of maxillo-mandibular retrusion and obstructive sleep apnea syndrome (pConclusionsOur study provides new insights on the impact of FGFR3 activating mutations on craniofacial growth, and highlights anatomo-functional correlation between the severity of craniofacial features and obstructive sleep apnea syndrome.