Sindrome de Crouzon
Sindrome de Crouzon
     Crouzon syndrome (CS) is the most common craniosynostosis syndrome and requires a comprehen-
     sive management strategy for the optimization of care and functional rehabilitation. This report pre-
     sents a case series of 6 pediatric patients diagnosed with CS who were treated with distraction
     osteogenesis (DO) to treat serious functional issues involving severe orbital proptosis, an obstructed
     nasopharyngeal airway, and increased intracranial pressure (ICP). Three boy and 3 girls were 8 months
     to 6 years old at the time of the operation. The mean skeletal advancement was 16.1 mm (range, 10
     to 27 mm) with a mean follow-up of 31.7 months (range, 13 to 48 months). Reasonable and success-
     ful outcomes were achieved in most patients as evidenced by adequate eye protection, absence of
     signs and symptoms of increased ICP, and tracheostomy tube decannulation except in 1 patient. Com-
     plications were difficult fixation of external stabilizing pins in the distraction device (n = 1) and
     related to surgery (n = 4). Although DO can be considered very technical and can have potentially
     serious complications, the technique produces favorable functional and clinical outcomes in treating
     severe CS.
     Ó 2017 American Association of Oral and Maxillofacial Surgeons
     J Oral Maxillofac Surg -:1.e1-1.e12, 2017
More than 100 craniosynostosis syndromes have been                           nostoses related to multiple fibroblast growth factor
described, with an estimated birth prevalence of 1 in                        receptor 2 (FGFR2) mutations and was first reported
2,000 to 2,500.1 Syndromic craniosynostoses are esti-                        by Louis Edouard Octave Crouzon in 1912 who
mated to constitute 15% of all craniosynostoses and                          described craniofacial dysostosis with the triad of
more than 180 craniosynostosis syndromes have                                calvarial deformities, facial anomalies, and exoph-
been identified to date, of which approximately 8%                           thalmos in a woman and her son.2,3
of cases are inherited or familial.2 Crouzon syndrome                          Over the years, conventional craniofacial surgical
(CS) is one of the most common syndromic craniosy-                           techniques, such as strip craniectomy, fronto-orbital
Received from the University of Malaya, Kuala Lumpur, Malaysia.                 Conflict of Interest Disclosures: None of the authors have a rele-
  *Associate Professor and Consultant, Oro-Craniomaxillofacial               vant financial relationship(s) with a commercial interest.
Research and Surgical Group, Faculty of Dentistry.                              Address correspondence and reprint requests to Dr Hariri: Oro-
  yProfessor and Senior Consultant, Oro-Craniomaxillofacial                  Craniomaxillofacial Research and Surgical Group, Faculty of
Research and Surgical Group, Faculty of Dentistry.                           Dentistry, University of Malaya, 50603 Kuala Lumpur, Malaysia;
  zConsultant     Neurosurgeon,     Division   of    Neurosurgery,           e-mail: firdaushariri@um.edu.my
Department of Surgery, Faculty of Medicine.                                  Received August 1 2017
  xClinical Specialist, Oro-Craniomaxillofacial      Research   and          Accepted November 17 2017
Surgical Group, Faculty of Dentistry.                                        Ó 2017 American Association of Oral and Maxillofacial Surgeons
  kSenior Lecturer, Mathematics Division, Centre for Foundation              0278-2391/17/31449-0
Studies in Science.                                                          https://doi.org/10.1016/j.joms.2017.11.029
  {Professor and Senior Consultant, Division of Neurosurgery,
Department of Surgery, Faculty of Medicine.
                                                                      1.e1
1.e2                                                        DISTRACTION OSTEOGENESIS IN CROUZON SYNDROME
advancement, and Le Fort III procedures, have               and comprehensive assessment from neurosurgeons,
proved reliable to treat symptomatic syndromic cra-         maxillofacial surgeons, pediatric ophthalmologists,
niosynostosis. However, in severe conditions, large         pediatric otolaryngologists, pediatric respiratory
segmental advancement requires the gap to be grafted,       therapists, anesthetists, and clinical genetics. As part
stabilized, and closed primarily because inadequate         of the presurgical workup, the baseplates for the mid-
stability secondary to soft tissue restriction and unsta-   face internal devices were pre-bent and fixed on a 3D
ble bone segment fixation can cause graft resorption,       skull bio-model for each patient to allow surgical
thus causing relapse and creating less than an ideal        simulation and vector determination and minimize
long-term outcome.                                          operating time.
   The introduction of distraction osteogenesis (DO)           Based on specific functional indications, 5 patients
to craniofacial surgery has provided a reliable surgical    underwent monobloc DO to achieve intracranial
alternative in achieving superior segmental advance-        decompression, orbital protection, and nasopharyn-
ment compared with conventional techniques in treat-        geal airway relief and 1 patient underwent posterior
ing functional issues in syndromic craniosynostosis.        cranial vault DO to address the isolated increase in ICP.
Apart from obviating an additional bone grafting               To treat the 3 functional issues optimally, 4 patients
procedure, the natural process of bone regeneration         (patients 1 to 4) with severe structural deficiency
through gradual traction simultaneously produces            received a combination of bilateral internal midface
new histogenesis, which overcomes the soft tissue           devices and a rigid external device (Synthes, Oberdorf,
limitation.                                                 Switzerland) and 1 patient (patient 5) with moderate
   In cases of severe CS, patients can present with         functional discrepancies received only bilateral inter-
major functional disturbances, namely increased intra-      nal midface distractors (Synthes). Because patient 6
cranial pressure (ICP), severe exorbitism with the          presented only with signs of a potential progressive
inability to achieve eyelid closure for orbital protec-     increase in ICP, posterior cranial vault expansion was
tion, and serious upper airway obstruction with             indicated using internal distractors (Synthes).
progressive obstructive sleep apnea (OSA) secondary            All procedures were performed through the coronal
to a severely hypoplastic maxilla, which eventually         approach. Before the osteotomy, the internal devices
might require a tracheostomy to bypass the obstructed       were placed to mark the planned placement site. In
airway. As such, the indication for each major surgery      patients who underwent monobloc DO, the osteot-
in pediatric patients with this condition should be         omy was performed at the fronto-orbital region before
agreed to by the craniofacial team members because          completion of the Le Fort III osteotomy and completed
the procedure carries substantial mortality and             through the maxillary tuberosity cut intraorally. Once
morbidity risks.4                                           the midface was separated, the internal devices were
   This report presents a case series of pediatric          fixed and trial activation was performed to ensure
patients with CS who underwent craniomaxillofacial          correct vector trajectory. For patients receiving an
DO to manage functional deficiencies, with the focus        external device, bilateral protective titanium temporal
on surgical indications, choice of device, and the          plates were fabricated and placed subperiosteally to
distraction protocol and its associated complications.      prevent temporal bone perforation before the external
                                                            frame was placed at the end of surgery. Patient 6, who
                                                            underwent posterior cranial vault expansion, had a
Report of Cases
                                                            similar presurgical workup of the distractor applica-
   This study was approved by the medical ethics com-       tion on his skull bio-model for surgical simulation
mittee of the Faculty of Dentistry of the University of     and vector determination.
Malaya (Kuala Lumpur, Malaysia; institutional review           All patients were admitted to the pediatric intensive
board reference number DF OS1516/0053[P]) and all           care unit for 3 to 5 days for close monitoring before
participants signed an informed consent agreement.          being transferred to the pediatric ward. The mean
   This report describes 6 pediatric patients with CS       latency period was 2.5 days (range, 1 to 3 days). The
(3 boys and 3 girls; age range, 8 months to 6 years).       activation rate was 1 mm per day and the mean skeletal
Five patients (patients 1 to 5) presented with              advancement was 16.1 mm (distraction range, 10 to
increased ICP, severe exorbitism with an inability to       27 mm), with a mean consolidation period of 24 weeks
achieve eyelid closure, and OSA secondary to a narrow       (12 to 48 weeks). Mean follow-up was 31.7 months
nasopharyngeal space, and 1 patient (patient 6) pre-        (range, 13 to 48 months). Reasonable and successful
sented with increased ICP only. All patients underwent      functional rehabilitation outcomes were documented
a standard craniofacial protocol as routinely practiced     in most patients as evidenced by the absence of
in the authors’ multidisciplinary craniofacial clinic,      signs and symptoms of increased ICP, ability for eyelid
which involved computed tomographic (CT) analysis,          closure to achieve adequate eye protection, tracheos-
fabrication of a 3-dimensional (3D) skull bio-model,        tomy tube decannulation, resolved OSA, and an
HARIRI ET AL                                                                                                              1.e3
acceptable facial appearance (Figs 1-6), except in                     the test was that there would be no difference in the
patient 3 who had restricted maxillary movement.                       median of the pre- and postsurgical phases, which
   The objective outcomes of 5 patients (patients 1 to                 can be expressed as H0:v(j)pre = v(j)post. The results
5) who underwent monobloc DO were measured                             presented in Table 1 show non-rejection of the H0
using various parameters from the pre- and postopera-                  and indicate successful functional rehabilita-
tive CT scans compared with the respective distrac-                    tion outcomes.
tion amount of each case to support favorable                             Complications were difficult fixation of external sta-
functional and clinical outcomes. For patient 6, who                   bilizing pins in the distraction device (n = 1) and
underwent posterior vault DO, a marked increase of                     related to surgery (n = 4), namely lateral rectus muscle
the intracranial perimeter was found when the pre-                     impingement and cerebrospinal fluid (CSF) leak in
and postoperative values were compared (Fig 7). For                    patient 2, restricted maxillary movement in patient
the assessment of patients 1 to 5, the distance from                   3, and localized wound infection in patient 6. The
the sella turcica to the nasion, the distance from the                 management of these complications is comprehen-
sella turcica to the deepest concavity of the maxilla,                 sively described in the Discussion section. All data
and the point between the borders of the orbital floor                 for the DO protocol, complications, and management
and the lateral orbital border were measured at the                    are presented in Table 2.
presurgical and post-distraction phases (Fig 8). They
were labeled v(j) = (vj1, vj2, . vjN), where j = 1, 2, 3
indicates the variables described earlier and N = 5 is
                                                                       Discussion
the total number of patients considered. The variable
for the pre- and postsurgical phase were denoted as                       CS is usually diagnosed at birth or during infancy
v(j)pre and v(j)post, respectively, and the statistical com-           based on a thorough clinical evaluation, the identifica-
parison of these variables was performed using the                     tion of characteristic physical findings, and results
Wilcoxon signed rank test (IBM SPSS Statistics 24;                     from different specialized tests. Nevertheless, an expe-
IBM Corp, Armonk, NY). The null hypothesis (H0) of                     rienced ultrasonographer or obstetrician also can
detect the early evidence of cranial suture fusion dur-                ophthalmologic assessment and funduscopy are para-
ing ultrasound or detailed 3D scanning procedures.                     mount to detect any potential pathologic process of
   The molecular genetic protocol for the diagnosis of                 orbital proptosis, and a tonometer can be used to
CS includes first-line tests of FGFR2 exons IgIIIa and                 check intraocular pressure. Respiratory issues require
IgIIIc followed by second-line tests of FGFR2 exons                    nasoendoscopy for the assessment of the nasopharyn-
3, 5, 11, and 14 to 17 and FGFR3 Pro250Arg and                         geal airway and, if indicated, polysomnography for the
Ala391Glu as proposed by Wilkie et al.5 Clinically, cra-               diagnosis of OSA.
nial malformation with shallow orbits and ocular prop-                    Increased ICP with hydrocephalus would necessi-
tosis are diagnostic features of CS.                                   tate ventriculoperitoneal shunting, severe orbital
   Plain radiographs and CT scans also can assist in the               proptosis might indicate temporary tarsorrhaphy,
diagnosis and assessment of CS.6 A copper beaten                       and respiratory difficulty would necessitate a contin-
appearance, enlarged hypophyseal cavity, maxillary                     uous airway pressure device, a nasal stent, or a trache-
hypoplasia, and mandibular prognathism can be visu-                    ostomy depending on the severity and the specific
alized on a lateral skull plain radiograph. Brain CT                   anatomic obstruction.
scan can provide a detailed image of diffuse indenta-                     Extent of surgical treatment of the deformities of CS
tion of the inner table of the skull and the degree of hy-             depends on how functionally and severely the patients
drocephalus. CT scan also can be used for the                          are affected according to their age. Surgical interven-
fabrication of a 3D bio-model for the actual structural                tion can be performed as staged or combined to
evaluation and surgical simulation.                                    address these functional issues. For example,
   Intracranial evaluation can be performed using plain                increased ICP alone can be treated by posterior cranial
radiography, CT scanning, or magnetic resonance im-                    vault expansion,7,8 increased ICP with orbital
aging. Cranial bone thinning or a copper beaten                        proptosis might require fronto-orbital advancement
appearance strongly suggests increased ICP. Clinical                   with or without cranioplasty,9 and increased ICP in
HARIRI ET AL                                                                                                                 1.e7
FIGURE 7. Comparison of the cranial perimeter of patient 6 who underwent posterior vault distraction osteogenesis. A, Preoperative.
B, Postoperative.
Hariri et al. Distraction Osteogenesis in Crouzon Syndrome. J Oral Maxillofac Surg 2017.
the presence of orbital proptosis and hypoplastic                      new histogenesis compared with conventional
maxilla might require a monobloc as practiced in the                   surgical procedures.14 All patients in the present study
authors’ center. Surgery can be performed convention-                  had their 3D skull bio-model fabricated to allow surgi-
ally or combined with a DO technique, which is indi-                   cal simulation and vector determination to optimize
cated for superior structural expansion. Patients with                 the outcome of surgery. The pre-bending of the dis-
asymptomatic CS can undergo orthodontic treatment                      tractor footplates for the internal device and presurgi-
with or without orthognathic surgery to correct dental                 cal simulation proved critical because it contributed to
and jaw discrepancies at growth maturation.                            the precision of device fixation and correct segmental
   The application of DO in treating craniofacial defor-               movement to ensure a favorable final outcome and
mity was first reported in 1992.10 Since then, the ben-                decrease operating time.
efits of this technique in treating syndromic                             The selection of devices in the present patients was
craniosynostosis as reported in the literature are                     based on device suitability and functional indications.
similar to those in the present study, which include                   Increased ICP was assessed by history, presence of
marked improvements in functional parameters                           signs or symptoms, imaging analysis, and ophthalmo-
involving eye protection, preventing the increase of                   logic assessment. For the eye, the patients’ ability to
ICP, and treating airway deficiency.11-14 The                          achieve eyelid closure was assessed and documented
technique has major advantages, which include                          and supplemented with eye examinations that
producing      superior     advancement,     obviating                 included optic disc condition and cup-to-disc ratio
additional bone grafting, and achieving simultaneous                   through funduscopy. Airway function was assessed
1.e8                                                                   DISTRACTION OSTEOGENESIS IN CROUZON SYNDROME
FIGURE 8. Variables measured from computed tomograms of each patient. A, Anatomic points of the computed tomographic midsagittal view.
B, Anatomic points at the most lateral point of the orbit from the computed tomographic sagittal slice.
Hariri et al. Distraction Osteogenesis in Crouzon Syndrome. J Oral Maxillofac Surg 2017.
by history from the guardians, symptoms of OSA,                        but might not be suitable for a very young infant and
airway endoscopic evaluation, overnight pulse oxime-                   carries the risk of stabilizing pin perforation of a very
try, and, when indicated, polysomnography.                             thin temporal bone surface.15 The internal device is
   The combination of internal and external devices                    compact and more suitable for small patients but pro-
provides stable advancement at the central and lateral                 vides only a single vector, thus requiring bilateral fixa-
midface components and the internal device can act as                  tion, and has been reported to have the disadvantage
a temporary rigid fixation during the consolidation                    of central component relapse because it provides
period after the external frame is removed at the end                  only lateral retention.15
of the activation phase. Nevertheless, it is vital to                     The amounts of advancement achieved in the pre-
comprehensively assess each case before the selection                  sent patients (range, 10 to 28 mm) can be considered
of a device because different distractors can differ in                substantially superior to the conventional surgical
suitability, vector control, and limitations. The                      technique and comparable to those of another larger
external device focuses more on the central compo-                     craniofacial DO study.14 The distracted bone space
nent and can be considered to have multiple vectors                    was noted to be filled with new bone (Fig 9). All
                                                                                                                                                                            antibiotic prescription
                                                                                                 Lateral orbital wall box
                                                                                                                                                                                                                                                                                                                                                                                                        the ability to achieve eyelid closure with stable
movement
                                                                                                                                                                           Local wound
                                                                                                   of maxilla
                                                                                                                                                                             infection
                                                                                                   CSF leak
                                                                                           48
                                                                                           48
33
29
                                                                                                                                                                     19
                                                                                                                                                                     13
48
16
                                                                                                                                                                     31
                                                                                                                                                                     12
10
11
                                                                                                                                                                     15
                                                                                                                                                                     11
                                                                                                                                                                     1
                                                                                                                                                                     1
                                                                                                                                                                                                                                                                                                                                                                                                        bone perforations.19
                                                                                           2
                                                                                           3
                                                                                                                                                                     3
                                                                                                                                                                     3
Ext + Int
                                                                                                                                  Ext + Int
                                                              Device
Monobloc DO
Monobloc DO
                                                                                                                                                                     Monobloc DO
                                                              Procedure
(yr)
                                                                                                                                                                     6
                                                                                                                                                                     2
                                                                                                                                                                     5
                                                                                                                                                                     6
FIGURE 9. Posterior cranial vault distraction osteogenesis in patient 6. A, Distractor before activation. B, Trial activation of bilateral distractors
showing an increased gap with favorable segmental movement. C, Gap filled with new bone after 3-month consolidation phase.
Hariri et al. Distraction Osteogenesis in Crouzon Syndrome. J Oral Maxillofac Surg 2017.
who undergo surgery at a young age, a long-term                                 In conclusion, the introduction of the DO technique
study by Gwanmesia et al20 showed that the distrac-                           provides a reliable surgical alternative and a predict-
tion procedure produced long-term stable advance-                             able outcome in the functional rehabilitation of severe
ment and functional gains.                                                    CS. However, its application requires comprehensive
HARIRI ET AL                                                                                                                                           1.e11
                                                                               DIAGNOSIS
                                                    Antenatal                                   At birth
                                                    Ultrasound suspicion                        Clinical features
                                                    3D detailed scan                            Genec study
ASSESSMENT
TEMPORARY INTERVENTION
SURGICAL INTERVENTION
                      Raised ICP         Orbital proptosis*       OSA**           Raised ICP              Raised ICP              Orbital Proptosis
                                                                                      +                        +                         +
                                                                                Orbital proptosis*     Orbital proptosis*              OSA**
                                                                                      +
                                                                                     OSA**
presurgical planning               and      carries        considerable                 8. Salokorpi N, Vuollo V, Sinikumpu JJ, et al: Increases in cranial vol-
                                                                                           ume with posterior cranial vault distraction in 31 consecutive
morbidity risks.
                                                                                           cases. Neurosurgery 81:803, 2017
                                                                                        9. Derderian C, Seaward J: Syndromic craniosynostosis. Semin
                                                                                           Plast Surg 26:64, 2012
                                                                                       10. McCarthy JG, Schreiber J, Karp N, et al: Lengthening the human
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1.e12                                                                   DISTRACTION OSTEOGENESIS IN CROUZON SYNDROME
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