Evaluation of the Pierre Robin Sequence Mandible Using Computed Tomography

Bienstock, Daniel; Ayyala, Ramesh S.; Eisig, Sidney B.; Perrino, Michael A.

doi:10.1016/j.joms.2016.06.093

Cited by 2 publications

(10 citation statements)

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“…A Hotelling test again revealed that the ramus was the mandibular structure most affected by changes in Sox9 dosage ( Figure 6 N). Although milder, these alterations in mandibular ramus morphology are reminiscent of phenotypes observed in PRS patients, as quantified by a number of studies ( Bienstock et al., 2016 ; Chen et al., 2015 ; Chung et al., 2012 ; Suri et al., 2010 ; Susarla et al., 2017 ; Volk et al., 2020 ; Zellner et al., 2017 ; Table S4 ; Figure S6 C). Finally, to address whether enhancer knockout results in failure to thrive, we weighed pups up to weaning age (P20–P25) and detected a reduction in weight gain for mEC1.45 knockout animals ( Figure 6 O).…”

Section: Resultsmentioning

confidence: 88%

Loss of Extreme Long-Range Enhancers in Human Neural Crest Drives a Craniofacial Disorder

et al. 2020

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Summary Non-coding mutations at the far end of a large gene desert surrounding the SOX9 gene result in a human craniofacial disorder called Pierre Robin sequence (PRS). Leveraging a human stem cell differentiation model, we identify two clusters of enhancers within the PRS-associated region that regulate SOX9 expression during a restricted window of facial progenitor development at distances up to 1.45 Mb. Enhancers within the 1.45 Mb cluster exhibit highly synergistic activity that is dependent on the Coordinator motif. Using mouse models, we demonstrate that PRS phenotypic specificity arises from the convergence of two mechanisms: confinement of Sox9 dosage perturbation to developing facial structures through context-specific enhancer activity and heightened sensitivity of the lower jaw to Sox9 expression reduction. Overall, we characterize the longest-range human enhancers involved in congenital malformations, directly demonstrate that PRS is an enhanceropathy, and illustrate how small changes in gene expression can lead to morphological variation.

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Section: Resultsmentioning

confidence: 88%

Loss of Extreme Long-Range Enhancers in Human Neural Crest Drives a Craniofacial Disorder

et al. 2020

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“…Statistical significance data were not published. Bienstock et al (2016) published a retrospective cohort study in 2016 using CT scans to compare 5 patients with PRS with a mean age of 2.2 months to a control group of patients with a mean age of 12.2 months (Bienstock et al, 2016). Syndromic versus nonsyndromic PRS was not specified, and age matching was not performed.…”

Section: Discussionmentioning

confidence: 99%

“…They reported that infants with PRS had significantly shorter mean ramus heights (21 vs 30 mm, P ¼ .02) as well as significantly shorter mean mandibular body lengths (35.6 vs 45.2 mm). Gonial and intergonial angles were not reported (Bienstock et al, 2016). Chung et al (2012) published a retrospective study using CT-based 3D images to compare mandibles from 5 patients with PRS (mean age: 3.20 years) and 5 patients with Treacher Collins syndrome (mean age: 5.40 years) to 6 age-and sexmatched control children with normal mandibles (mean age: 5.00 years).…”

Section: Discussionmentioning

confidence: 99%

“…Previous efforts to quantify mandibular morphologic differences in patients with PRS have largely been based on 2D images, with limited studies evaluating exact anatomical characteristics using advanced imaging modalities (Figueroa et al, 1991; Shen et al, 2012; Bienstock et al, 2016). Published studies that have utilized 3D techniques do not provide data directly relevant to MDO (Chung et al, 2012; Bienstock et al, 2016; Susarla et al, 2017; Zellner et al, 2017; Susarla et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

“…At present, however, there are no standardized, quantitative metrics characterizing the mandibular morphology of patients with PRS. Previous studies have used anthropometric analysis, lateral cephalography, 2-dimensional (2D) computed tomography (CT) scans, and linear measurements from 3-dimensional (3D) scans to evaluate mandibles of patients at various ages and compare these measurements with those from either patients with other syndromes or patients with normal mandibles (Figueroa et al, 1991; Chung et al, 2012; Shen et al, 2012; Bienstock et al, 2016; Paes et al, 2016; Susarla et al, 2017; Zellner et al, 2017). However, these studies have not provided measurements that can be used to guide early surgical planning.…”

Section: Introductionmentioning

confidence: 99%

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Quantification of Mandibular Morphology in Pierre Robin Sequence to Optimize Mandibular Distraction Osteogenesis

Volk

Davis

Narawane

et al. 2020

The Cleft Palate Craniofacial Journal

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Background: Mandibular distraction osteogenesis (MDO) is the primary surgical intervention to treat airway obstruction in Pierre Robin sequence (PRS). Current morphologic studies of PRS mandibles do not translate into providing airway management decisions. We compare mandibles of infants with nonsyndromic PRS to controls characterizing morphological variances relevant to distraction. We also examine how morphologic measurements and airway grades correlate with airway management. Methods: Patients with PRS under 2 months old were age and sex matched to controls. Demographic and perioperative data, and Cormack-Lehane airway grades were recorded. Computed tomography scans were used to generate mandibular models. Bilateral condylions, gonions, and the menton were identified. Linear and angular measurements were made. Wilcoxon rank sum and 2-sample t tests were performed. Results: Twenty-four patients with PRS and 24 controls were included. Seventeen patients with PRS required MDO. PRS patients had shorter ramus heights (16.7 vs 17.3 mm; P = .346) and mandibular body lengths (35.3 vs 39.3 mm; P < .001), more acute gonial angles (125.3° vs 131.3°; P < .001), and more obtuse intergonial angles (94.2° vs 80.4°; P < .001) compared to controls. No significant differences were found among patients requiring MDO versus conservative management nor among distracted patients with high versus low airway grades. Conclusion: Our study examines the largest and youngest PRS population to date regarding management of early airway obstruction with MDO. Our findings indicate that univector mandibular body distraction allows for normalization in nonsyndromic patients with PRS, and airway obstruction management decisions should remain clinical.

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Evaluation of the Pierre Robin Sequence Mandible Using Computed Tomography

Cited by 2 publications

References 0 publications

Loss of Extreme Long-Range Enhancers in Human Neural Crest Drives a Craniofacial Disorder

Loss of Extreme Long-Range Enhancers in Human Neural Crest Drives a Craniofacial Disorder

Quantification of Mandibular Morphology in Pierre Robin Sequence to Optimize Mandibular Distraction Osteogenesis

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