Exploratory Associations of Targeted Genetic Variants with Cephalometric Airway Parameters in Children with Skeletal Class II Sleep-Disordered Breathing Symptoms

TL;DR

This study explores how specific genetic variants may be linked to airway features in children with skeletal Class II malocclusion and sleep-disordered breathing symptoms.

Contribution

It identifies associations between targeted genetic variants and hyoid-position-related cephalometric measurements in a pediatric population with skeletal Class II and SDB symptoms.

Findings

Variant carriers showed higher C3–H measurements compared to non-carriers.

HH1 measurements were higher but not statistically significant in variant carriers.

Genetic variants were found in 27% of participants across several genes.

Abstract

What are the main findings?
Targeted sequencing identified selected genetic variants in candidate pathways in a subset of children with skeletal Class II mandibular retrognathia and symptoms of sleep-disordered breathing.Variant carriers showed differences in cephalometric airway–related measures, most notably in hyoid-position–associated measurements.

Targeted sequencing identified selected genetic variants in candidate pathways in a subset of children with skeletal Class II mandibular retrognathia and symptoms of sleep-disordered breathing.

Variant carriers showed differences in cephalometric airway–related measures, most notably in hyoid-position–associated measurements.

What are the implications of the main findings?
These exploratory data support integrated craniofacial and host-susceptibility phenotyping in pediatric sleep-disordered breathing and may help generate testable hypotheses for future studies.Larger controlled, ideally longitudinal cohorts with standardized phenotyping and appropriate multivariable analyses are required to validate genotype–phenotype patterns and clarify potential clinical relevance.

These exploratory data support integrated craniofacial and host-susceptibility phenotyping in pediatric sleep-disordered breathing and may help generate testable hypotheses for future studies.

Larger controlled, ideally longitudinal cohorts with standardized phenotyping and appropriate multivariable analyses are required to validate genotype–phenotype patterns and clarify potential clinical relevance.

Background/Objectives: Pediatric sleep-disordered breathing (SDB) is influenced by craniofacial morphology and host susceptibility. Evidence integrating cephalometric airway features with targeted genetic variation in symptomatic skeletal Class II children remains limited. We explored whether children with skeletal Class II mandibular retrognathia and SDB symptoms harbor selected genetic variants and whether carriers show distinct cephalometric airway characteristics. Methods: This cross-sectional study included 48 children with skeletal Class II malocclusion, mandibular retrognathia, and snoring/mouth-breathing symptoms. Craniofacial and airway parameters were assessed on lateral cephalograms. SDB burden was evaluated by a baseline home sleep study (respiratory event index, REI). Targeted sequencing screened TNFRSF1A, PSTPIP1, SLC6A4 (5HTT), ACE, APOE, IRS1, and additionally PHOX2B and PMP22. Exploratory group comparisons used Student’s t-test. Results: Variants were identified in 13/48 participants (27%) in TNFRSF1A, PSTPIP1, SLC6A4, ACE, APOE, and IRS1; none were detected in PHOX2B or PMP22. C3–H was higher in variant carriers (39.90 ± 6.40 vs. 36.48 ± 3.95 mm; p < 0.05). HH1 (perpendicular distance from the hyoid bone to the C3–RGN line) was higher but not significant (16.99 ± 7.58 vs. 14.61 ± 5.25 mm; p > 0.05). Conclusions: In this clinically screened pediatric skeletal Class II cohort with SDB symptoms, selected genetic variants co-occurred with specific hyoid–cervical cephalometric features. Given the cross-sectional design, absence of a control group, and small number of carriers, findings are exploratory and require replication in larger, controlled cohorts with standardized phenotyping.

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