UitnodigingUitnodiging curriculum vitae SHAPE AND SURGERY MICROSOMIA ON CRANIOFACIAL voorvoor hethet bijwonenbijwonen vanvan dede Britt Pluijmers was born on the 16th of November 1987 in Cardi (UK), and spent part of openbareopenbare verdedigingverdediging vanvan hethet her childhood in Belgium before moving to the Netherlands. She graduated from Libanon ON CRANIOFACIAL MICROSOMIA proefschriftproefschrift Lyceum high school in Rotterdam in 2005. In 2006 she started medical training at the Erasmus University Hospital in Rotterdam SHAPE AND SURGERY OnOn CraniofacialCraniofacial MicrosomiaMicrosomia (EMC). During her studies she was a board member of the Education committee EMC, and ShapeShape andand SurgerySurgery did voluntary work in the Palestinian Territories. In her third year, under direct supervision of dr. Koudstaal, she started research at the department of Oral and Maxillofacial surgery at the EMC led by em. prof. dr. van der Wal. doordoor BrittBritt PluijmersPluijmers Her Master thesis was carried out under the guidance of prof. Dunaway, at the Great Ormond Street Hospital in London (UK). During her internship at the department of Oral BRITT PLUIJMERS OpOp woensdagwoensdag 1111 septemberseptember 20192019 and Maxillofacial surgery EMC, she started this thesis, with dr. Koudstaal as co-promotor omom 11:3011:30 and prof. dr. Wolvius as promotor. In 2013, she graduated Cum Laude from medical school, and commenced her dentistry inin dede Prof.Prof. AndriesAndries QueridozaalQueridozaal studies at Radboud University, Nijmegen, from which she graduated in 2016. vanvan hethet OnderwijscentrumOnderwijscentrum vanvan Simultaneously, she was a board member of Promeras, the PhD committee of the hethet ErasmusErasmus MedischMedisch CentrumCentrum Erasmus MC. In 2015 she started her Oral- and Maxillofacial surgery training (under WytemawegWytemaweg 8080 tete RotterdamRotterdam supervision of prof. dr. Wolvius) at the Erasmus Medical Center in Rotterdam and the St. Elisabeth Hospital in Tilburg (under supervision of J.P.O. Scheerlinck). She was a member of the organizational committee of the JOD NWHHT in 2017. NaNa aa oopoop vanvan dede promotiepromotie bentbent uu At present, she is in her senior year of her training, and a member of the implementation vanvan harteharte welkomwelkom opop dede receptiereceptie committee for the new curriculum for Oral- and Maxillofacial surgery residents. BrittBritt PluijmersPluijmers Britt is married to Coen Iordens and proud mother to Michiel. She has 3 awesome MathenesserlaanMathenesserlaan 371a371a brothers. 30233023 GDGD RotterdamRotterdam 06474804990647480499 [email protected]@gmail.com ParanimfenParanimfen SuzanneSuzanne DeetmanDeetman [email protected]@deetman.nl MelvynMelvyn PluijmersPluijmers [email protected]@gmail.com B.I. PLUIJMERS B.I. BrittBritt Pluijmers Pluijmers Cover Cover v6.indd v6.indd 4 4 24-7-201924-7-2019 16:56:36 16:56:36 Naamloos-2Britt Pluijmers 1-4 Cover v6.indd 1-3 24-7-2019 16:56:17 24-7-2019 17:05:31 On Craniofacial Microsomia Shape and Surgery Britt Irene Pluijmers PSM 20190527 Proefschrift Britt Pluijmers.indd 1 24-07-19 15:04 © 2019, Britt Irene Iordens-Pluijmers ISBN: 978-94-6380-426-4 Artwork cover: Margot Annuschek Lay-out: RON Graphic Power, www.ron.nu Printing: ProefschriftMaken || www.proefschriftmaken.nl Financial support for the printing and distribution of this thesis was kindly supported by: Afdeling Mondziekten, Kaak- en Aangezichtschirurgie Erasmus Medisch Centrum Erasmus Medisch Centrum Nederlandse Vereniging voor Mondziekten, Kaak- en Aangezichtschirurgie Geistlich Bio-Oss® en Geistlich Bio-Gide® All rights reserved. No parts of this publication may be reported or transmitted, in any of form or by any means, without the permission of the author. PSM 20190527 Proefschrift Britt Pluijmers.indd 2 24-07-19 15:04 On Craniofacial Microsomia shape and surgery Craniofaciale microsomie vorm en chirurgie Thesis to obtain the degree of Doctor from the Erasmus University Rotterdam by command of the rector magnificus Prof.dr. R.C.M.E. Engels and in accordance with the decision of the Doctorate Board. The public defence shall be held on Wednesday 11th of September 2019 at 11:30 hrs by Britt Irene Pluijmers born in Cardiff, Wales (UK) Erasmus University Rotterdam PSM 20190527 Proefschrift Britt Pluijmers.indd 3 24-07-19 15:04 Doctoral Committee: Promotor: Prof. dr. E.B. Wolvius Other members: Prof. D.J. Dunaway Prof. dr. G.J. Kleinrensink Prof. dr. I.M.J. Mathijssen Copromotor: Dr. M.J. Koudstaal Paranymphs: S. Deetman M.B.D. Pluijmers PSM 20190527 Proefschrift Britt Pluijmers.indd 4 24-07-19 15:04 “On wednesdays we wear pink” PSM 20190527 Proefschrift Britt Pluijmers.indd 5 24-07-19 15:04 PSM 20190527 Proefschrift Britt Pluijmers.indd 6 24-07-19 15:04 Contents Part I General introduction 11 Part II Population 27 Chapter 1 Craniofacial and extracraniofacial anomalies in craniofacial microsomia: A multicenter study of 755 patients 29 Part III Shape 49 Chapter 2 Characterizing the skull base in craniofacial microsomia using principal component analysis 51 Chapter 3 Using principal component analysis to describe the midfacial deformities in patients with craniofacial microsomia 71 Chapter 4 Describing the mandible in patients with craniofacial microsomia based on principal component analysis and thin-plate-spline video analysis. 93 Chapter 5 Is there a difference in orbital volume between affected and unaffected sides in patients with unilateral craniofacial microsomia 109 Part IV Surgery 119 Chapter 6 Mandibular reconstruction in the growing patient with unilateral craniofacial microsomia: a systematic review 121 Chapter 7 Surgical correction of the midface in craniofacial microsomia. 143 Part 1: a systematic review PSM 20190527 Proefschrift Britt Pluijmers.indd 7 24-07-19 15:04 PSM 20190527 Proefschrift Britt Pluijmers.indd 8 24-07-19 15:04 Chapter 8 Surgical correction of the midface in craniofacial microsomia. 163 Part 2: Is the maxillary canting and its surgical correction in patients with CFM correlated to the mandibular deformity? Chapter 9 Surgical correction of craniofacial microsomia: Evaluation of interventions in 565 Patients at three major Craniofacial units 175 Part V General discussion 195 Part VI Summaries 205 Summary 206 Samenvatting 209 Part VII Appendices 213 Publications 214 Presentations 217 PhD Portfolio 218 Dankwoord 220 PSM 20190527 Proefschrift Britt Pluijmers.indd 9 24-07-19 15:04 PART I PSM 20190527 Proefschrift Britt Pluijmers.indd 10 24-07-19 15:04 I General introduction PSM 20190527 Proefschrift Britt Pluijmers.indd 11 24-07-19 15:04 General introduction General introduction Craniofacial microsomia (CFM) is the second most common congenital craniofacial malformation following cleft lip and palate.1,2 In 1952, Goldenhar characterized the disorder as a triad of accessory tragus, mandibular hypoplasia and epibulbar dermoid.3 Other names for the disorder are ‘otomandibular dysostosis’ and ‘first and second branchial arch syndrome’.4,5 A term often found in genetics literature is ‘oculo-auriculo- vertebral syndrome’ (OAVS) as proposed by Gorlin.6 However, in the surgical field, hemifacial microsomia and nowadays craniofacial microsomia is most commonly used. The deformity is characterized by predominantly asymmetrical hypoplasia of struc- tures derived from the first and second pharyngeal arches, leading to a distinct scoliosis of the facial skeleton. The first pharyngeal arch gives rise to the mandible, maxilla, zygoma, trigeminal nerve, muscles of mastication, and the inner ear and a part of the external ear, whereas the second pharyngeal arch gives rise to the facial nerve, stapes, styloid process, portions of the hyoid bone, facial musculature, and the majority of the external ear.7 Other anomalies seen in patients with CFM include malformations of the vertebrae, cervical spine, cardiorespiratory system, urogenital system, limbs, central nervous system and gastrointestinal system. Most often reported are skeletal, cardiac and renal anomalies. CFM is most often regarded as a unilateral malformation; however, facial structures have been reported to be involved bilaterally in 10% of cases.8-10 Previous studies suggested that, in most cases, the contralateral side is abnormal as well, although not truly hypoplastic.10-15 The etiology of CFM has not yet been clarified. Well-known hypotheses are local haemorrhage of the stapedial artery16 and disturbed migration of cranial neural crest cells.17,18 Several possible genes, proteins and or pathway signalling disregulations have been suggested including BPAX1, Foxi3 and loss of Hedgehog signaling.16-19 However, an increased risk is found in a history of multiple pregnancies, second-trimester vaginal bleeding and risk factors associated with poverty.4 Leading to the believe that the etiology might include genetic and non-genetic factors, in line with an oligogenic or even a multifactorial etiology.7 Although CFM usually occurs sporadically, familial cases compatible with autosomal dominant and autosomal recessive patterns of inheritance have been described. Patients with CFM are phenotypically heterogeneous; their dysmorphologies range from minor to severe. Therefore, a comprehensive classification is needed to describe the severity of the different anomalies to ensure clear communication among physicians in various specialties and researchers. The Pruzansky classification was the first of such systems, which was later subcategorized by