ORIGINAL ARTICLE Pediatric/Craniofacial Facial Malformation in Crouzon’s Syndrome Is Consistent with Cranial Base Development in Time and Space Xiaona Lu, MD* Antonio Jorge Forte, MD, PhD† Background: In Crouzon’s syndrome, cranial base deformities begin sequentially Rajendra Sawh-Martinez, in the anterior cranial fossa initially, and later to the posterior cranial base. Facial MD, MHS‡ characteristics are likely related to cranial base development. The temporal cor- Sarika Madari, BS‡ relation between cranial base development and facial features is in need of clarifi- Robin Wu, BS‡ cation in Crouzon’s patients, to clarify initial sites of deformity, which may impact Raysa Cabrejo, BS‡ surgical decision making. Derek M. Steinbacher, Methods: Thirty-six computed tomography scans of unoperated Crouzon’s syn- MD, DMD‡ drome patients and 54 controls were included and divided into 5 age-subgroups. Michael Alperovich, MD‡ All the planes used for analysis were set as perpendicular to a defined “midplane” Nivaldo Alonso, MD, PhD§ to offset the confounding factor caused by potential asymmetry. John A. Persing, MD‡ Results: The angle between Sella-Nasion plane and Frankfort horizontal plane was significantly increased before 6 months of age P( = 0.014), with an average 70% (P < 0.001) increase ultimately into adulthood. The angle between SN and maxil- lary plane and the angle between Sella-Nasion and occlusal planes increased consis- tently through infancy to adulthood (124% and 42%, respectively, both P < 0.001). The relative angle of mandibular plane to Frankfort horizontal plane increased before 6 months (28%, P = 0.007) with a peak timeframe from 2 to 18 years. Facial lateral curvature related measurements indicate the whole face is inclined posteri- orly and inferiorly direction in relation to the anterior cranial base. Conclusion: Crouzon’s facial malformation development is synchronous and posi- tionally correlational with cranial base deformity. It transmitted from orbit to man- dible, with the most evident morphologic changes are in the orbit and midface. (Plast Reconstr Surg Glob Open 2018;6:e1963; doi: 10.1097/GOX.0000000000001963; Published online 4 October 2018.) INTRODUCTION methods have provided a better understanding of struc- Craniosynostosis, exophthalmos, hypoplastic midface, tural characteristics of these facial malformations. As facial and mandibular prognathism characterize Crouzon’s syn- characteristics are likely to be related to cranial base de- drome.1–6 In recent years, 3-dimensional morphometrics velopment,7,8 this connection needs to be clarified further in pathologic conditions such as Crouzon’s syndrome, to clarify which are primary and secondary deformities to un- From the *Chinese Academy of Medical Sciences, Peking Union derstand pathogenesis of the deformity and anatomic trail Medical College, Plastic Surgery Hospital, Beijing, China; of influence. †Division of Plastic and Reconstructive Surgery, Mayo Clinic In our previous study of Crouzon’s syndrome, cranial Florida, Jacksonville, Fla.; ‡Section of Plastic and Reconstructive base deformity was noted to begin in the anterior cranial Surgery, Yale School of Medicine, New Haven, Conn.; and fossa, and with further growth deformity was evident in §Department of Plastic Surgery, University of São Paulo, São posterior cranial vault. This resulted in a more severe de- Paulo, Brazil. formation in the posterior fossa. In view of the develop- Received for publication August 1, 2018; accepted August 7, mental position, correlation between facial and cranial 2018. Copyright © 2018 The Authors. Published by Wolters Kluwer Health, Disclosure: The authors have no financial interest to Inc. on behalf of The American Society of Plastic Surgeons. This declare in relation to the content of this article. The Article is an open-access article distributed under the terms of the Creative Processing Charge was paid for by the authors. Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in Supplemental digital content is available for this ar- any way or used commercially without permission from the journal. ticle. Clickable URL citations appear in the text. DOI: 10.1097/GOX.0000000000001963 www.PRSGlobalOpen.com 1 PRS Global Open • 2018 base structure,8,10,11 the question may be asked, does the close the mouth for who underwent general anesthesia, more severe posterior skull base deformity cause a more and therefore had open-mouth posture during computed significant corresponding facial deformity? tomography scanning, http://links.lww.com/PRSGO/A886; The purpose of this study was to examine this question see table, Supplemental Digital Content 3, which displays and define the interactive craniofacial influences which the definition of landmarks, cephalometric distances, ra- change with age, by objectively analyzing craniofacial, tios, angles, and planes, http://links.lww.com/PRSGO/A887; temporal developments in a series of unoperated Crou- see table, Supplemental Digital Content 4, which displays zon’s syndrome patients. measurements results in age subgroups analyses, http:// links.lww.com/PRSGO/A888). PATIENTS AND METHODS Statistical analyses were carried out in Microsoft Excel (v.2016, Microsoft Corp., Redmond, Wash.). t Test was This is a longitudinal study performed in accordance used for comparison of continuous variables. All statistical with the Yale University Human Investigation Committee tests were 2-sided, statistical significance was set atP < 0.05. (HIC 1101007932). Computed tomographic scans were obtained from all subjects without any previous surgical intervention. Thirty-six preoperative computed tomo- RESULTS graphic scans of Crouzon’s syndrome patients, and 54 age- and sex-matched, controls without confounding dis- Demographic Date ease were included. All the computed tomography scans A total of 90 computed tomographic scans were includ- are divided into 5 subgroups based on age: 0–6 months, ed (Crouzon, n = 36; control, n = 54). The 5 age subgroups 6 months to 2 years, 2 to 6 years, 6–18 years, and 18–62 consisted of 0–6 months, 6 months to 2 years, 2–6 years, years old. Age and sex were rematched in each age-sub- 6–18 years, and 18–62 years old. The mean age of the 2 group to confirm comparability. Demographic informa- groups was as follows: Crouzon, 10.84 ± 14.70 years with a tion was tabulated. range from 3 days to 62 years old; and control, 8.53 ± 13.22 Digital Imaging and Communications in Medicine years with a range from 5 days to 62 years old. The Crou- data were digitized and manipulated using Mimics and zon’s group consisted of 14 males and 22 females, and in 3-matics software (version 19.0; Materialise, Leuven, Bel- the control group were 29 males and 25 females (Table 2). gium). Before the initial data acquisition for this study, the observer (X.L.) went measurements training until Craniofacial Planes Angular Measurements the Pearson correlation coefficients of both interobserv- Angular Analysis Based on Sella-Nasion Plane er (compared with a practiced observer) at 0.95, and Before 6 months of age, the angle between Sella-Nasion intraobserver error was less than 0.05. All the landmark plane (SN; Table 3) and Frankfort horizontal plane (FH) points, generated lines, angles, and planes were cho- was significantly increased 144% P( = 0.013), with an aver- sen and produced twice by the same observer, in both age 70% increasing (P < 0.001) in whole life of Crouzon’s Crouzon’s syndrome and control groups, with indepen- syndrome compared with controls. The angle between dent verification by 3 additional observers (A.F., R.S., SN and maxillary plane (Mx) and the angle between SN and J.P.). and occlusal plane (Occ) increased consistently through Abbreviation and definitions of measurements, and infancy to adulthood with the most marked increase from detailed anatomic planes setting process were shown in 6 months to 2 years (104%, P = 0.003) and from 6 years Table1 and Supplemental Digital contents 1-3 (see fig- to 18 years old [60% (P = 0.014)] when compared with ure, Supplemental Digital Content 1, which displays all age- and sex-matched controls. The angle between SN the planes used in this study were set as perpendicular to and mandibular plane (MP) increased 7.64° (P = 0.036) the midplane to offset the confounding factors caused by before 6 years old, and increased twice that amount sub- potential asymmetry, http://links.lww.com/PRSGO/A885; sequently [peak time at 6–18 years (44%, P = 0.002)]. The see figure, Supplemental Digital Content ,2 which displays angle between SN and mandibular ramus plane (MRP) the “interactive rotate” function in 3-matic was used to had increased in the 2–6 years age group and between Table 1. Definition of Anatomic Planes Abbreviation Variable Definition SN Sella-Nasion plane The plane passing through sella and nasion landmarks and perpendicular to midsagittal plane FH Frankfort horizontal Plane The Frankfort horizontal plane is defined by a plane that passes the midpoint of both Orbita (Orbitar and Orbital) landmarks and the midpoint of the two Porion (Porionr and Porionl) landmarks, and perpendicular to midsagittal plane Mx Maxillary plane The maxillary plane is defined by a plane that passes the anterior nasal spine and posterior nasal spine landmarks, and perpendicular to midsagittal plane Occ Occlusal plane The occlusal plane is defined by a plane that passes the mean of upper and lower incisor land- marks in both sides and the mean of upper and lower molar landmarks in both side, and perpendicular to midsagittal plane MP Mandibular plane The mandibular plane is defined by a plane that passes the menton and the mean of both Gonion landmarks, and perpendicular to midsagittal plane MRP Mandible ramus plane The plane passes the mean of bilateral gonions and the mean of bilateral condylions, and is perpendicular to midsagittal plane 2 Lu et al.