Velopharyngeal Anatomy in 22q11.2 Deletion Syndrome: A Three-Dimensional Cephalometric Analysis

Abstract

Objective-22q11.2 deletion syndrome is the most common genetic cause of velopharyngeal dysfunction (VPD). Magnetic resonance imaging (MRI) is a promising method for noninvasive, three-dimensional (3D) assessment of velopharyngeal (VP) anatomy. The purpose of this study was to assess VP structure in patients with 22q11.2 deletion syndrome by using 3D MRI analysis.Design-This was a retrospective analysis of magnetic resonance images obtained in patients with VPD associated with a 22q11.2 deletion compared with a normal control group.Setting-This study was conducted at The Children's Hospital of Philadelphia, a pediatric tertiary care center.Patients, Participants-The study group consisted of 5 children between the ages of 2.9 and 7.9 years, with 22q11.2 deletion syndrome confirmed by fluorescence in situ hybridization analysis. All had VPD confirmed by nasendoscopy or videofluoroscopy. The control population consisted of 123 unaffected patients who underwent MRI for reasons other than VP assessment. Interventions-Axial and sagittal T1-and T2-weighted magnetic resonance images with 3-mm slice thickness were obtained from the orbit to the larynx in all patients by using a 1.5T Siemens Visions system.Outcome Measures-Linear, angular, and volumetric measurements of VP structures were obtained from the magnetic resonance images with VIDA image-processing software.Results-The study group demonstrated greater anterior and posterior cranial base and atlantodental angles. They also demonstrated greater pharyngeal cavity volume and width and lesser tonsillar and adenoid volumes.Conclusion-Patients with a 22q11.2 deletion demonstrate significant alterations in VP anatomy that may contribute to VPD. Keywords 22q11.2 deletion syndrome; magnetic resonance imaging; velopharyngeal dysfunctionNormal velopharyngeal (VP) function is dependent upon multiple factors. Neuromuscular function, velar anatomy, and overall morphology of the VP port all contribute to the process of VP valving. The structural and functional integrity of each of these factors ultimately determines the adequacy of the VP mechanism as a whole. The VP port is composed of soft tissues (e.g., adenoids, lateral and posterior pharyngeal walls, velum) and their underlying bony structures (e.g., maxilla, basicranium, upper cervical spine). Alterations in one or more of these structures may be a feature of some craniofacial syndromes and may play a critical role in the pathogenesis of associated VP dysfunction (VPD).With an estimated incidence of 1 in 4000 births, the 22q11.2 deletion syndrome, also known as velocardiofacial syndrome (VCFS), is the most common genetic cause of VPD (McDonaldMcGinn et al., 1999). Affected patients present with a spectrum of functional and anatomic abnormalities that may contribute to alterations in VP valving, including cleft palate or submucosal cleft palate, palatopharyngeal hypotonia, platybasia, adenoid hypoplasia, and cervical spine abnormalities (Havkin et al., 2000). To date, however, the relative contribution of each of th...

The role of cephalometry in assessing velopharyngeal dysfunction in velocardiofacial syndrome

“…However, in our study, only approximately 11% of the subjects had platybasia, whereas the remaining 89% had a normal cranial base angle. This is in discordance with the majority of previous reports describing platybasia as a characteristic finding in VCFS 13. However, a careful review of the literature reveals that platybasia may not always be seen in association with VCFS: Glander and Cisneros14 did not observe an abnormal cranial base angle in individuals with VCFS, and in a recent study by Dalben and colleagues,15 on comparing the cephalometric measurements of patients with and without VCFS, an obtuse cranial base angle was observed in the study group but it was not statistically significant when compared to the control subjects.…”

“…Because Need ratio and OPD/VL are closely related, our findings are similar to this previous report 13. Upper cervical spine abnormalities, the prevalence of which is higher in patients with craniofacial syndromes, may increase the osseous pharyngeal depth predisposing the affected patients to VPD 13, 16. C1–C2 vertebral anomalies are reported to occur in above 97% of the FISH‐positive 22q11.2 deletion patients; the most frequent findings reported include lack of fusion of the anterior and/or posterior arch of C1, upswept C2 lamina and spinous process, and C2–C3 fusion 17.…”

“…Similarly, the majority of subjects in the present study had a greater Need ratio, which is the ratio between nasopharyngeal depth and velar length. Because Need ratio and OPD/VL are closely related, our findings are similar to this previous report 13. Upper cervical spine abnormalities, the prevalence of which is higher in patients with craniofacial syndromes, may increase the osseous pharyngeal depth predisposing the affected patients to VPD 13, 16.…”

“…Greater osseous pharyngeal depth (OPD) to VL ratio has been noted in patients with 22q11.2 deletion 13. Similarly, the majority of subjects in the present study had a greater Need ratio, which is the ratio between nasopharyngeal depth and velar length.…”

“…The velum is reported to be short and thin in patients with VCFS, thus resulting in increased pharyngeal depth and incomplete closure of the velopharyngeal port, but thus far the exact incidence of this in VCFS individuals has not been clarified. A comparative study of retrospective analysis of MRI findings in VCFS patients with VPD and a normal control group by Ruotolo and colleagues13 revealed no significant differences in velar length and thickness in the 22q11.2 deletion group, but it is to be noted that the study included only five subjects with VCFS, a very small number. In our study, 50% of the subjects had decreased velar length, and thus we believe that a shortened velum contributes to VPD by increasing NPD.…”