The spectrum of Apert syndrome: phenotype, particularities in orthodontic treatment, and characteristics of orthognathic surgery.

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ssBioMed CentHead & Face Medicine
Open AcceCase Study
The spectrum of Apert syndrome: phenotype, particularities in
orthodontic treatment, and characteristics of orthognathic surgery
Ariane Hohoff*†1, Ulrich Joos†2, Ulrich Meyer†3, Ulrike Ehmer†1 and
Thomas Stamm†1
Address: 1Department of Orthodontics, University Hospital, Westfalian Wilhelms-University, Münster, Germany, 2Department of
Craniomaxillofacial Surgery, University Hospital, Westfalian Wilhelms-University, Münster, Germany and 3Department of Cranio-and-Maxillo
Facial Surgery, Heinrich Heine University, Düsseldorf, Germany
Email: Ariane Hohoff* - hohoffa@uni-muenster.de; Ulrich Joos - joos@uni-muenster.de; Ulrich Meyer - ulrich.meyer@med.uni-duesseldorf.de;
Ulrike Ehmer - ehmer@uni-muenster.de; Thomas Stamm - stammt@uni-muenster.de
* Corresponding author †Equal contributors
Abstract
In the PubMed accessible literature, information on the characteristics of interdisciplinary orthodontic and surgical
treatment of patients with Apert syndrome is rare. The aim of the present article is threefold: (1) to show the spectrum
of the phenotype, in order (2) to elucidate the scope of hindrances to orthodontic treatment, and (3) to demonstrate
the problems of surgery and interdisciplinary approach.
Children and adolescents who were born in 1985 or later, who were diagnosed with Apert syndrome, and who sought
consultation or treatment at the Departments of Orthodontics or Craniomaxillofacial Surgery at the Dental School of
the University Hospital of Münster (n = 22; 9 male, 13 female) were screened. Exemplarily, three of these patients (2
male, 1 female), seeking interdisciplinary (both orthodontic and surgical treatment) are presented. Orthodontic
treatment before surgery was performed by one experienced orthodontist (AH), and orthognathic surgery was
performed by one experienced surgeon (UJ), who diagnosed the syndrome according to the criteria listed in OMIM™.
In the sagittal plane, the patients suffered from a mild to a very severe Angle Class III malocclusion, which was sometimes
compensated by the inclination of the lower incisors; in the vertical dimension from an open bite; and transversally from
a single tooth in crossbite to a circular crossbite. All patients showed dentitio tarda, some impaction, partial eruption,
idopathic root resorption, transposition or other aberrations in the position of the tooth germs, and severe crowding,
with sometimes parallel molar tooth buds in each quarter of the upper jaw.
Because of the severity of malocclusion, orthodontic treatment needed to be performed with fixed appliances, and mainly
with superelastic wires. The therapy was hampered with respect to positioning of bands and brackets because of
incomplete tooth eruption, dense gingiva, and mucopolysaccharide ridges. Some teeth did not move, or moved
insufficiently (especially with respect to rotations and torque) irrespective of surgical procedures or orthodontic
mechanics and materials applied, and without prognostic factors indicating these problems. Establishing occlusal contact
of all teeth was difficult. Tooth movement was generally retarded, increasing the duration of orthodontic treatment.
Planning of extractions was different from that of patients without this syndrome.
In one patient, the sole surgical procedure after orthodontic treatment with fixed appliances in the maxilla and mandible
was a genioplasty. Most patients needed two- jaw surgery (bilateral sagittal split osteotomy [BSSO] with mandibular
Published: 8 February 2007
Head & Face Medicine 2007, 3:10 doi:10.1186/1746-160X-3-10
Received: 30 June 2006
Accepted: 8 February 2007
This article is available from: http://www.head-face-med.com/content/3/1/10
© 2007 Hohoff et al; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0),
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Page 1 of 24
(page number not for citation purposes)
setback and distraction in the maxilla). During the period of distraction, the orthodontist guided the maxilla into final
position by means of bite planes and intermaxillary elastics.

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To our knowledge, this is the first article in the PubMed accessible literature describing the problems with respect to
interdisciplinary orthodontic and surgical procedures. Although the treatment results are not perfect, patients
undergoing these procedures benefit esthetically to a high degree.
Patients need to be informed with respect to the different kinds of extractions that need to be performed, the increased
treatment time, and the results, which may be reached using realistic expectations.
Background
Apert syndrome, which was well described by a number of
authors earlier [1,2] is a rare congenital anomaly, appear-
ing with a frequency of 1 in 55,000 to 90,909 live births
[1,3,4] is one of the five craniosynostosis syndromes
caused by allelic mutations of the fibroblast growth-factor
receptor 2 (FGFR2) [5].
Externally, this progessive disease of growth is character-
ized by acrocephaly, syndactyly, and typical features in the
orofacial region [6].
The lips are crossbow-shaped or trapezoidal, and the
lower lip may seem to protrude [7].
The midface is retruded, which is already marked at birth
[8]. The Class III discrepancy is progressive [9], the maxilla
is hypoplastic [10] in all three dimensions, [7] and anteri-
orly there is edge-to-edge contact or an open bite
[8,11,12].
Cephalometrically, a common craniofacial asymmetry
can be diagnosed [13]. Maxillary height is extremely short,
and upper facial height markedly reduced, whereas total
facial height is increased as compared with the norm [11].
The teeth are crowded [12], and there is a mean dental
developmental delay of 0.96 years, with a range of 0.5 to
2.9 years [14]. The delayed eruption may be secondary to
the crowding, stacking, and displacement of the teeth
within the alveolus, which is often wide to accommodate
the tooth buds in two rows [7]. A primary defect in tooth
eruption secondary to the "mesenchymal disorder" in
Apert syndrome also must be considered [7].
In the mandible, thickening of the gingiva and delayed
eruption are also observed, but to a lesser degree [7].
There are bulbous lateral swellings in the palate, which
until now were not properly named in the anatomic
nomenclature [15] and which might be so prominent that
they become a food trap [7]. This posterior notching [7]
could suggest a cleft palate [12], but is actually a pseudo
cleft palate. A true cleft palate occurs in 23.5% of the cases
[4]. A cleft soft palate or bifid uvula may be present in
The morphological defects may induce functional defects,
such as sleep apnea, disturbances of breathing, feeding,
speech [17], and lip closure [7].
Despite the intrasyndromic similarities, there is a high
degree of variable phenotypical expression [4,10,18].
The aim of the present case study is to show
- the clinical variablity of Apert syndrome (spectrum of
the phenotype),
- implications for hindrances in orthodontic therapy, and
- characteristics of surgery and interdisciplinary treatment
approach.
Table 1 gives an overview of the general treatment concept
for patients with Apert syndrome at the University Hospi-
tal of Münster, which allows for individual adaptions.
This paper refers to treatment stages 3 to 5 given in Table
1.
Methods
Children and adolescents who were born in 1985 or later,
who were diagnosed with Apert syndrome, and who
sought consultation or treatment at the Department of
Orthodontics or Craniomaxillofacial Surgery at the Den-
tal School of the University Hospital of Münster (n = 22;
9 male, 13 female) were screened.
Exemplarily, three of these patients (2 male, 1 female),
seeking interdisciplinary (both orthodontic and surgical
treatment) were chosen because their malocclusions were
representative of the whole clinical spectrum of Apert syn-
drome and their treatment at stages 3–5 (Table 1) thus
covered the whole therapeutic spectrum, ranging from
orthodontic treatment and genioplasty only to two-jaw
surgery with distraction (Table 2). Orthodontic treatment
of these patients was performed by one experienced
orthodontist (AH); orthognathic surgery was executed by
one experienced surgeon (UJ), who diagnosed the syn-
drome according to the criteria listed in Online Mende-
lian Inheritance in Man [19].Page 2 of 24
(page number not for citation purposes)
approximately 75% of the patients [16].

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Case descriptions
Case 1
History (treatment stages 1 and 2 according to Table 1):
- < Age 3.0: (Surgical) treatment alieno loco.
- Age 6.2: LeFort III surgery and protraction mask.
The treatment sequence is illustrated in figures 1, 2, 3, 4,
5, 6, 7, 8.
Case 2
History (treatment stages 1 and 2 according to Table 1):
- < Age 7.0: Surgical treatment alieno loco.
- Age 7.2: Frontal advancement and protraction mask
coincident with orthodontic extrusion of 11 and 21.
The treatment sequence is illustrated in figures 9, 10, 11,
12, 13, 14.
Case 3
History (treatment stages 1 and 2 according to Table 1):
- < Age 8.5: (Surgical) treatment alieno loco
- Age 8.5: LeFort II and face mask.
The treatment sequence is illustrated in figures 15, 16, 17,
18, 19, 20, 21, 22, 23.
Discussion of exemplarily chosen cases
Case 1
Although transposition of teeth 22 and 23 was accepted
and torque of teeth 21 and 23 and occlusal contact of the
right premolars could not be established, the patient was
reported to have benefited considerably from the ortho-
dontic treatment, both esthetically and functionally.
Despite long distances for the teeth to move and 3 years of
treatment, no root resorptions developed.
Thirty-six months' treatment was quite long as compared
with nonsyndromic patients, nevertheless quite short con-
Table 1: Interdisciplinary treatment concept for patients with Apert syndrome at the University Hospital of Münster (individual
adaptions allowed).
Stage Age Procedure
1 3–6 months Eradicative-osteoclastic method [35]
2 7–10 years LeFort III osteotomy +
Frontal advancement +
Protraction face mask immediately postoperatively for 6–12 months (rapid stenosis, problems with anchorage of the
orthodontic appliance due to exfoliation of deciduous teeth, and eruption of permanent teeth)
Early LeFort III osteotomy might help to avoid a (second) LeFort III osteotomy at stage 5, and thus reduce surgical risks.
3 > 9 years Extraction therapy
4 > 10 years Orthodontic treatment (preparation for orthognathic surgery), retention
5 > 16 years Orthognathic surgery
Table 2: Essentials of treatment of 3 patients in this study.*
Case Sex Age of insertion of
fixed orthodontic
appliance (years)
Treatment time
with fixed
appliance (years)
Age at surgical
intervention
(years)
Kind of surgery
1 Female 11.4 3.0 13.3 Genioplasty
2 Male 13.7 1.4 Planned, but not yet
performed
Planned, but not yet performed: maxilla: distraction;
mandible: BSSO†/mandibular setback
3 Male 15.2 1.3 18.6 Maxilla: distraction (advancement + rotation);
mandible: BSSO†/mandibular setback
*These patients were chosen exemplarily because their malocclusions were representative of the whole clinical spectrum of Apert syndrome and
their treatment at stages 3–5 (see Table 1) thus covered the whole therapeutic spectrum ranging from orthodontic treatment and genioplasty Page 3 of 24
(page number not for citation purposes)
exclusively to 2-jaw surgery with distraction.
† BSSO = bilateral sagittal split osteotomy.

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sidering the severity of the initial malocclusion. In case
reports on Apert syndrome, Gugny [21,22] reported a
treatment time of 33 months (with further treatment with
fixed appliances advised); Rynearson [23] treated a
patient with Crouzon syndrome for 58 months; and Mat-
sumoto et al. [24] reported a treatment time of 10 years.
In contrast to the present case, where an upper anterior
tooth was transposed, Rynearson's patient came out with
a more perfect result (having only one tooth in crossbite),
which was achieved with a multisegmental LeFort I oste-
otomy (i.e., a surgical setup) and 61 % more orthodontic
treatment time [23]. Gugny's result, after 33 months of
orthodontic treatment, showed residual spaces, rotations,
midline deficiency and crossbite [21,22]; nevertheless, the
improvements of the initial malocclusion were great.
The need for extractions in patients with Apert syndrome
is described in various articles [21-23,25]. The teeth
selected for extraction, however were different from the
present case, where unerupted canines were extracted:
Gugny [21,22] and Gugny and Vi Fane [25] decided to
extract the upper lateral incisors and premolars in cases,
where the canines already had erupted; Rynearson [25]
extracted one premolar and several molars, but in his
patient with Crouzon syndrome, too, the canines already
had erupted.
In 1991, Ferraro [7] pointed out that certain patients with
Apert syndrome might benefit from genioplasty to pro-
vide an orthognathous appearance, which has been
proved by the present case.
Age 8.8. Extraorally: Hypertelorism, vertical excess of the lower third of the face, trapezoidal upper lip, forced lip closure pos-sible, but difficultFigure 1
Age 8.8. Extraorally: Hypertelorism, vertical excess of the lower third of the face, trapezoidal upper lip, forced lip closure pos-
sible, but difficult. Intraorally: Dentitio tarda, crowding, Angle Class III with dental compensation by retrusion of lower incisors,
circular open bite with unilateral crossbite.Page 4 of 24
(page number not for citation purposes)

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An alternative to the practised compensating orthodontic
treatment with genioplasty would have been surgical cor-
rection of the open bite. This might have reduced the total
treatment time, but would have increased the patient's
surgical risks.
The hand deformity and the decrease in arm mobility
made it difficult to floss–even brush the teeth [7] which
might explain the difficulties in maintaining oral hygiene.
Another reason might be inanition due to the extended
treatment time.
Case 2
Practising orthodontic treatment phased to orthognathic
surgery implies the risk of relapse and thus the need for
grinding prior to surgery in patients who do not wear their
retainers properly, but phasing orthodontic treatment to
orthoganthic surgery might have psychologic benefits.
Orthognathic surgery implies certain risks, but it is some-
times necessary to improve a patient's appearance and
social adjustment [26].
Problems in maintaining oral hygiene were comparable
with those of case 1, probably for the same reasons.
Also comparable with case 1, case 2 also involved prob-
lems in establishing correct torque. Additional problems
with lack of rotation of teeth and decelerated tooth mobil-
ity in general made the orthodontic treatment of case 2
more difficult, and led to a more compromised result as
compared with case 1.
Treatment of case 2, like that of case 1 and for the same
reasons, required other than the "traditional" extraction
decisions.
For a discussion of the suggested orthognathic surgery, see
case 3.
Case 3
Initial tooth positions of case 3 were better than in cases 1
and 2. Orthodontic correction of the crossbite on the left
side was impossible because of lack of possible anchors
(primary absence of 21 after need for extraction due to idi-
opathic root resorption and additional idiopathic resorp-
tion of 24 and 25, prohibiting inclusion of these teeth
into the appliance).
We agree with other authors that in patients with Apert
syndrome, midface advancement will almost always be
required, and repeat cranial surgery is usually necessary
[7,17]. Midfacial surgery is also best postponed as long as
possible, but many children require surgery at around 4 to
6 years of age [17]. Early midface advancement has ana-
tomic and psychologic benefits [25] as well as functional
advantages such as reduction of sleep apnea [27,28].
However, the earlier midface surgery is performed, the
more likely it is that further operations will be needed
[17]. Meazzini et al. [9] described in a cephalometric
study that, after LeFort III osteotomy at younger than 10
years, the stability of the maxillary segment was remarka-
ble with neither detrimental nor beneficial effects on sub-
sequent growth. The authors concluded that the standard
LeFort III osteotomy in childhood is a stable and effec-
Age 10.8. Panoramic x-rayFigure 3
Age 10.8. Panoramic x-ray. Situation after extrusion of upper
central incisors. Lack of space for 13, 23, 38, 33, 43, and 48;
transposition of 22 and 23, second (supernumerary) canine in
Age 9.4. Situation after surgical exposure of upper central incisors at age 9.1Figure 2
Age 9.4. Situation after surgical exposure of upper central
incisors at age 9.1. Extrusion of upper central incisors with a
modified functional appliance (Fränkel 3), which was not
applied to treat the Class III, but only to extrude the upper
central incisors and to stretch the soft tissues to facilitate lip
closure.Page 5 of 24
(page number not for citation purposes)
tive–but generally not definitive–procedure. We do agree
with that, i.e. to our experience an early LeFort III osteot-
region 24, agenesis of 25. Ectopic position of 27.