Upper airways dysmorphology and obstructive sleeping apnea in Down syndrome

Abstract

Down syndrome (DS) is a complex genetic disorder caused by trisomy of chromosome 21 that alters the development of multiple systems, including craniofacial dysmorphologies. Mandibular hypoplasia, macroglossia and midfacial flatness are associated with higher prevalence of malocclusion and mouth breathing in DS. In this study, we assessed the morphology of the upper airways and tested whether alterations in the size and shape of the upper airways were associated with Obstructive Sleep Apnea (OSA), which compromises the quality of life in individuals with DS.To quantify differences in volume and shape of the upper airways, we obtained 3D reconstructions from head magnetic resonances scans in a cross‐sectional sample of 246 adult individuals, including 159 control euploid individuals and 87 individuals diagnosed with DS. Polysomnography tests were available in a subsample of individuals with DS, and AHI Index scores representing the number of apnea and hypopnea events per hour of sleep were used to indicate the severity of sleep apnea.Geometric Morphometric analyses based on the 3D coordinates of 15 anatomical landmarks located on the surface of the upper airways showed significant shape differences between DS and control individuals (P‐value=0.001), involving a retraction of the whole upper airways structure and a change in the angular inclination of the oropharynx region in individuals with DS. Volumetric analyses confirmed a significant 40% reduction in total upper airway volume in DS (P‐value<0.0001). Multivariate regression analysis showed that AHI scores explained 10.1% of upper airways morphological variation in DS, with a significant positive correlation between the shape and volume of the upper airways and the severity of OSA. Our study suggests that morphological biomarkers assessed from non‐invasive magnetic resonance images can be useful in diagnosing OSA, a sleep disturbance with high prevalence in DS that if treated correctly, can improve the quality of life of people with DS and prevent the appearance of early dementia.