| ObjectivesTreacher Collins syndrome(TCS)is an autosomal genetic disorder that may be associated with mutations in the TCOF1(about 80%-90%of cases),POLR1D or POLR1C(about 9%of cases)genes,resulting in abnormal development of the first and second parotid arches,with an incidence of approximately 1 in 50,000 live births[1-3].Patients with TCS clinically present with varying degrees of craniomaxillofacial skeletal dysplasia,such as zygomatic,maxillary and mandibular developmental malformations,and the abnormally developed craniomaxillofacial skeletons can lead to abnormal upper airway morphology and affect the upper airway function.The low incidence of TCS,its dissemination in China,and the diversity of its clinical phenotype make it challenging to investigate.Most of the previous studies have been reported in isolated cases,and few studies have analyzed the morphological characteristics of the midface skeleton and upper airway development and the effect of age on their development.Currently,the treatment of upper airway obstruction in patients with TCS is mainly based on low level evidence consisting of expert experience[4].It has been reported that extender distraction osteogenesis(DO)therapy is a commonly used and effective treatment for craniomaxillofacial dysplasia to improve craniomaxillofacial developmental deformities.However,there were no relevant studies exploring the effects of DO therapy in the midface laterally on the upper airway.Therefore,the aims of this study were to investigate the midface bones and upper airway morphology in patients with TCS using CT-based three-dimensional digital analysis technology,and compare them with the normal population in order to deepen the understanding of the disease and provide a morphological basis for the selection of treatment modalities;conduct age subgroup analysis of the developmental characteristics of the midface bones and upper airway,intended to provide reference for the selection of treatment timing in TCS patient and animal experiments were conducted to explore the effect of lateral distraction osteogenesis on the morphology of the upper airway for the first time.Methods1.TCS patients and normal population attending the Plastic Surgery Hospital of the Chinese Academy of Medical Sciences from January 2013 to July 2020 were selected,and a total of 33 cases met the inclusion criteria,including 14 cases in the TCS group and 19 cases in the control group.Patients were divided into three age subgroups:2-6 years,7-18 years,and 18 years or older.The differences in craniomaxillofacial measurement parameters in the midface,total upper airway volume and segment upper airway volumes were compared between the TCS and control groups;the age-related changes in the morphology of the skull base,maxilla,nose and upper airway in TCS patients were analyzed,and the correlation between age and upper airway volume was assessed.2.Exploratory animal experiment:10-month to 1-year-old Beagle dogs were selected as experimental animals for midface osteotomy and midface transverse distraction osteogenesis treatment.Changes in the midface bones and upper airway before and after distraction were compared.ProPlan CMF software(version 3.0;Materialize,Leuven,Belgium)was used to measure CT parameters,including the linear,angular cephalometric parameters,and upper airway volumes.ResultsCephalometric and morphological analysis of the midface revealed that,multiple transverse distances of TCS patients were significantly decreased when compared with the control group,such as the width of the maxillary base,the length of the maxillary complex,and some distances related to the nasal morphology(P<0.05);but the distance between bilateral orbitales increased in TCS group(P<0.05).Several anteroposterior distances in TCS group were decreased significantly when compared to control group and the distance between the skull base point and the posterior nasal spine was the most shortened(P<0.05).But there was no significant difference of the distance between nasion and anterior nasal spine,which represents anterior midface height between groups(P>0.05).The skull base angle and SNB angle(the angle between the sella point-nose root point-inferior alveolar seat point)of the TCS group both decreased when compared with the control group(P<0.05),but there was no significant difference in SNA angle(the angle between the sella point-nose root point-upper alveolar seat point)between the two groups(P>0.05).Total upper airway volume,nasal airway volume and nasal cavity volume were significantly decreased in the TCS patients group compared to the control group(P=0.037,P=0.013 and P=0.012,respectively).However,contrary to expectations,nasopharyngeal and oropharyngeal volumes were slightly decreased in TCS patients compared to controls,but the difference did not reach statistical significance(P>0.05).In addition,MaxW,MxUL,and ANS-PNS lengths were positively correlated with total upper airway volume,nasal airway volume,and nasal cavity volume(r>0.6,P<0.05).Total upper airway,nasal airway,and nasal cavity volumes were correlated with restricted internal nasal growth,as evidenced by reduced Ba-ANS,Ba-PNS,Ro-ANS,N-ANS,N-PNS,S-ANS,and S-PNS.The most significant intergroup differences in most craniomaxillofacial measurement parameters were observed in the 7-18 years age subgroup.In the subgroup older than 18 years,a statistical difference in upper airway volumes were observed between the two groups.Exploratory animal experiment:After midface bones osteotomy and midfacial transverse distraction treatment,several measurements of midface in experimental animals increased slightly compared with pre-distraction,such as INML-INMR increased about 12.9%after distraction(P=0.002).The mean nasal airway volume in the experimental animals after distraction was(34,679.85±5,392.44)mm3,which increased by 10.3%when compared with(31,435.32±5,668.5)mm3 before distraction,with a statistically significant difference(P=0.026).ConclusionsPatients with TCS are often associated with varying degrees of midfacial skeletal dysplasia,resulting in morphological changes and decreased volume of the upper airway,which can lead to impaired upper airway function.The transverse diameter,anterior-posterior diameter and several craniofacial angles of the midface of TCS patients were significantly decreased compared with those of the control group,which showed significant lateral hypoplasia of the nasal bone and maxilla,but no significant restriction of midface height development.The most obvious differences between TCS patients and control subjects occurred between 7 and 18years of age.Therefore,patients may benefit from surgery before upper airway obstruction occursAnimal experiments were conducted the first time to explore the effect of transverse distraction of the mid-facial skeleton with a distracter on the morphology of the upper airway,and the results showed that transverse distraction treatment of the midface is a feasible surgical method to increase the volume of the upper airway in experimental animals.However,the design of the extender and fixation screw should be improved in the future,and more experiments should be performed with the improved extender to demonstrate the feasibility of transverse distraction therapy.We aimed to provide a possible treatment option for patients with craniomaxillofacial dysplasia in the presence of midfacial skeletal transversal dysplasia. |
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