Oral Maxillofacial Surg Clin N Am 14 (2002) 477 – 490
Secondary grafting in the alveolar cleft patient
Amin Kazemi, DMD, MDa, Jeffrey W. Stearns, DMD,MDa,
Raymond J. Fonseca, DMDa,b,*
a
Department of Oral and Maxillofacial Surgery, Hospital of the University of Pennsylvania, 5th Floor White Building,
3400 Spruce Street, Philadelphia, PA 19104, USA
b
University of Pennsylvania School of Dental Medicine, 4001 Spruce Street, Philadelphia, PA 19104, USA
Historical perspective
The initial attempts at the treatment of alveolar
cleft defects date back to 1901, when Von Eiselberg
used pedicled bone to fill an alveolar defect [1].
Since that time, the complex management of a cleft
patient has advanced tremendously. These progres-
sions have been made possible by the visionary work
of multiple clinicians (Table 1). It is important to
recognize that these advancements were achieved in
the face of strong antagonists, who advocated no
treatment of the alveolar cleft defect. Continued
surgical advancements and refinement in techniques
have brought about controversies in the timing of
repair and the source of graft material. These con-
troversies however, have not detracted from the goal
of this treatment, which includes closing of the
oronasal fistula, establishing continuity between the
cleft segments, constructing proper alveolar contour,
preventing tooth loss caused by lack of periodontal
bone support, providing proper support for eruption
of teeth and orthodontic tooth movement, and cre-
ating firm support for the nasal floor [2]. Although
the repair of the alveolar cleft may be one of the last
considerations in the global treatment of a cleft
patient, if these goals are achieved, it provides
* Corresponding author. School of Dental Medicine,
Hospital of the University of Pennsylvania, 4001 Spruce
Street, Philadelphia, PA 19104.
E-mail address: fonseca@pobox.upenn.edu
(R.J. Fonseca).
1042-3699/02/$ - see front matter D 2002, Elsevier Science (USA). All rights reserved.
PII: S 1 0 4 2 - 3 6 9 9 ( 0 2 ) 0 0 0 4 2 - 0
tremendous enhancement of oral function and aes-
thetics for a cleft patient.
By reviewing the incidence, etiology, indications
for treatment, timing, source of graft material,
patient evaluation and assessment, presurgical ortho-
dontics, surgical techniques, postoperative care, and
complications, the authors hope to provide the
reader with a comprehensive understanding of alve-
olar clefts and their repair. This is an exciting area
of oral and maxillofacial surgery that allows for
integration and participation with multiple clinicians
from other specialties who are also intimately
involved in the care of the cleft patient. Proper
communication, understanding, and coordination
with these clinicians allows for optimum treatment
of these unique individuals.
Incidence and etiology
Among the many congenital birth defects, there
have been more than 250 different types of facial
clefting disorders described in the literature. The most
frequently reported defect is clefting of the palatine
bone and the alveolar process of the maxilla [3,4]. The
overall incidence of cleft lip and palate is reported at
1:750 live births in the United States [5]. Stratified
between the different ethnic groups the incidence is as
follows: African Americans, 1:2000; whites, 1:1000;
and Asians, 1:500 live births [6,7]. The location of the
clefting is usually on the left side of the maxilla
(left:right:bilateral 6:3:1). Out of the various combi-
nations of isolated cleft lip, isolated cleft palate, and
cleft lip and palate, the cleft lip and palate is the most
478 A. Kazemi et al. / Oral Maxillofacial Surg Clin N Am 14 (2002) 477–490

Table 1 The evaluation of the etiologic sources is important,

Historical perspective especially a genetic evaluation. The lack of attention
Date Author Contribution to associated anomalies may bring about improper
1908 Lexer [79] Free bone grafts genetic counseling and treatment.
1914 Drachter [80] Bone grafts to alveolar cleft
1931 Veau [81] Classification and attempt at
tibial graft to cleft palate
1955 Nordin et al Early alveolar cleft repair Treatment goals and objectives
with autogenous bone
1968 Jolley [28] Detrimental effects of early bone The functional and aesthetic problems associated
grafts on maxillary growth with cleft lip and palate depend on the size of the cleft
1972 Boyne and Protocol for secondary and whether it is unilateral or bilateral. The patient’s
Sands [82] bone graft quality of life can be affected in many ways. Some of
1983 Wolfe et al [74] Favorable results with the more common complaints include [19]
calvarial bone
1987 Nique, Alveolar graft with
 Food/fluids coming out of the nose
Fonseca [66] allogenic bone
 An inability to blow balloons or suck a straw
 A persistent smell or discharge from the nose
 Poor speech
common in occurrence (see box) [7]. In 75% of the  An inability to clean the teeth in the cleft area
cleft lip and palate occurrences, the cleft runs through  Decayed or deformed teeth in the cleft area
the alveolar ridge.  Missing or supernumerary teeth in the area
It is currently believed that less than 40% of the  Lack of bone support for teeth adjacent to
clefts of the lip and palate are of genetic origin [5,6]. the defect
Mutations in specific collagen genes in Stickler syn-  Poor alignment of the teeth of the lesser and
drome [8,9], homeodomain-containing protein PAX3 greater segments
in Waardenburg’s syndrome [10], and sonic hedgehog  Mobility and overgrowth of the premaxilla in
in midline craniofacial defects are examples of direct the bilateral case
genetic correlation with cleft lip and palate [11,12].  Lack of support for the alar base of the nose and
Environmental factors play a clear role in gene lip in the unilateral case
expression, which affects the phenotype [13]. For  Lack of support for the alar base, columella, and
example, Hwang et al report direct correlation lip in the bilateral case.
between maternal smoking and clefting [14]. Tolarova
and Harris found a decrease in clefting recurrence in These complaints allow the surgeons to create a list
mothers who took multivitamins (either the subjects of surgical goals that would alleviate these aesthetic
had a child with asyndromic cleft lip and palate or and functional issues. The following list has been
they or their partner had a cleft lip and palate) [15]. amassed from the available literature [2,19 – 21]:
Antiepileptic drugs also have been linked to clefting
[16]. Maternal alcohol consumption has been under 1. Close vestibular and palatal oronasal fistula
extensive debate as an etiologic factor [17]. Infections 2. Restore physiologic continuity of the dental
(rubella and toxoplasmosis) and growth factor defi- arch to enable oral and dental health to
ciency are among other environmental factors [18]. be maintained
3. Provide bone for stability and continuity of the
dental arch and premaxilla
4. Allow eruption of the permanent teeth or
Incidence of cleft lip and palate placement of dental implants through bone
graft
Cleft lip 5. Provide support for the lateral ala of the nose
0.29 per 1000 6. Allow for the orthodontic alignment of the
Cleft palate teeth
0.31 per 1000 7. Facilitate nasolabial muscle and soft tissue
Cleft lip and palate reconstruction
0.48 per 1000 8. Establish functional nasal airway
9. Provide support for the lip
 A. Kazemi et al. / Oral Maxillofacial Surg Clin N Am 14 (2002) 477–490
10. Prevent tooth loss caused by lack of perio-
dontal bone support.
It serves the practitioner well to have this list in
mind while constructing a unique surgical plan for a
unique cleft patient, thus providing an exceptional
treatment that satisfies most of the patients’ func-
tional, aesthetic, and psychosocial needs.
Timing of alveolar cleft grafting
To comprehend better the various ideologies con-
cerning the timing of the alveolar cleft grafting, one
first should have a firm grasp of its classification:
 Primary (0 – 2.5 years, usually at the time of
lip repair)
 Early secondary (2 – 5 years, before the eruption
of permanent incisors)
 Secondary (6 – 13 years, before the eruption of
the permanent canines)
 Late ( > 13 years, after the eruption of the per-
manent canines)
Select clinicians believe that primary bone grafting
has a vital role. It is their belief that with refinement in
surgical skills, the advent of bone morphogenetic
protein, and improvement in management of scar
tissue, the alveolar cleft grafting is sensible during
the primary time period [22 – 36a]. These studies seem
to have limited their focus to isolated components of
the deformity, however (asymmetry [36b], just narrow
clefts [37], and condition of adjacent teeth [38]). Most
studies of primary bone grafting indicate an imped-
ance on anterior and inferior growth of the maxilla and
poor angulations of the teeth and the premaxilla [22 –
29,31 – 35]. Jolley et al, in a study of the early bone
grafting of alveolar cleft, reported not only an ante-
roposterior growth limitation but also a higher pro-
pensity for cross-bites as a result [23].
The most common time to perform this surgery is
during secondary bone grafting. Numerous studies
have shown the efficacy of this procedure in satisfying
the previously mentioned goals [39 – 45]. The main
advantages of performing the surgery during this time
period are providing a high likelihood of success (up
to 98% in one study), providing excellent periodontal
attachment for the adjacent teeth, allowing for erup-
tion of the canine, allowing for orthodontic alignment,
and ensuring minimal impedance on facial growth
[39 – 45]. Posnick also mentions that waiting allows
maximum transverse (posterior) growth of the maxilla
479
to occur before bone grafting [21]. Ninety-five percent
of the anteroposterior and transverse growth of the
maxilla is completed by the age of 8 [21]. It is critical
to remember that in the case of cleft lip and palate the
sequence of eruption is usually delayed. Most sur-
geons agree that the preferred age of treatment is
contingent on the dental age rather than the chrono-
logic age.
Based on the limited studies in alveolar cleft
grafting during the early secondary period, it is
difficult to justify performing the bone graft on this
age group [46]. Boyne advocated alveolar cleft graft-
ing during this time period in cases in which the
permanent lateral or central incisors seem to be
erupting into the cleft, causing severe malposition of
the tooth and decreasing periodontal support of the
erupting tooth [47].
Although many studies have proved the late period
as a suboptimal age group to perform alveolar cleft
grafting, this group should not be excluded from such
treatment. The potential for successful surgery still
exists and in some situations one even could include
the alveolar cleft grafting with the patient’s orthog-
nathic (Le Fort I) procedure. In adult patients the
chance of successfully bone grafting an alveolar cleft
is less than in the adolescent. The main objective with
this population is to achieve oronasal closure, provide
continuity and stability of the maxillary arch, and
allow for possible implant restoration [48].
The fact that controversy exists in this area indi-
cates that much investigation still remains to be done.
As progression is made with better understanding of
maxillary growth, improvement and enhancement of
grafting materials, and refinement in surgical tech-
nique, one must reassess the success of this procedure
in the different age groups.
Grafting material and donor sites
Numerous variables affect the decision-making
process in choosing an appropriate donor site for
alveolar cleft bone grafting, including factors such
as the size of the cleft, the volume of bone needed,
whether teeth will erupt through the graft material, the
health of the donor site, and the healing potential of
the patient. Table 2 includes the various donor sites
and grafting materials along with their advantages and
disadvantages [25,49 – 75]. It is beyond the scope of
this article to discuss each of these in great detail, so
the Table 2 has been provided as a summary.
To enhance the osteoinductive ability of the graft
material, one can use platelet-rich plasma. This plas-
ma provides the graft material with more factors to
480 A. Kazemi et al. / Oral Maxillofacial Surg Clin N Am 14 (2002) 477–490

Table 2
Advantages and disadvantages of various graft material
Donor site / grafting material Advantages Disadvantages
Autogenous: greatest number of viable osteoprogenitor cells, which allow for early revascularization
(osteogenic, osteoconductive, osteoinductive)
Iliac crest Adequate quantity (uni- and bi-) Questionable effects on growth
Easily condensed and placed Possible gait disturbance
Proven successful results Postoperative hematoma
Little donor site morbidity Donor site morbidity
Two-team approach
Tibia Adequate volume (uni- and bi-) Concern with ambulation and
Quality similar to iliac crest epiphyseal injury
Predictable results
Two-team approach
Rib For infants Donor site morbidity
Two-team approach Unpredictable results
Cranial bone Adequate quantity (uni- and bi-) Donor site aesthetics/defect
(corticocancellous block graft) Less resorption (membranous bone) Stigma and fear for patient
Rapid vascularization Less cellular component
Predictable quality
Two-team approach
Mandibular symphysis Quantity adequate for uni- Limited amount of bone
Less resorption (membranous bone)
No external scars
Allogenic: derived from a genetically unrelated member of same species (osteoconductive, osteoinductive)
Comparable to autogenous No osteogenic potential
Allows for eruption of teeth Delayed incorporation
Avoids donor site morbidity
Alloplastic: inert foreign body material (osteoconductive, osteoinductive)
Avoids donor site morbidity Delayed healing
Inability of teeth to erupt

enhance the progenitor cell transformation to osteo-
blasts. If the graft survives the early complications of
infection and integrates into the cleft defect, the only
variable that remains is the volume of bone that
resorbs over time. This becomes an important factor,
especially when prosthetic reconstruction, such as
implant placement, comes into play. It is necessary
to perform a secondary bone grafting procedure
before implant placement to provide for adequate bulk
and contour.
Patient evaluation and assessment
malpositioned teeth in the region of the cleft, cross-
bites, caries, oral hygiene, position and mobility of the
premaxilla, and the adequacy of the soft tissue for
tension-free closure [46,76]. If this evaluation reveals
that the patient has lateral or central incisors whose
eruption is in jeopardy secondary to large cleft defects,
the patient must undergo grafting earlier to salvage
these teeth. At this stage the surgeon must choose an
appropriate flap design and grafting material along
with possible donor site based on the evaluation.
Radiographic evaluation includes panoramic,
occlusal, and periapical films of the cleft region.

A patient with an alveolar defect should be eval- Presurgical orthodontic care

uated for the repair of the alveolar cleft in the late
primary and early mixed dentition period. The evalu-
ation of a cleft patient starts with a thorough history
and physical examination, along with all the past
anesthetic and surgical history. The focused examina-
tion should evaluate the previous repairs, any oronasal
fistula, the alar support, the size of the alveolar defect,
Two major orthodontic considerations intimately
integrate with the timing of the alveolar cleft grafting:
the correction of cross-bites and the alignment of the
anterior teeth [77,78]. If posterior cross-bites exist
secondary to narrowed transverse dimension of the
maxilla, maxillary expansion may be performed
 A. Kazemi et al. / Oral Maxillofacial Surg Clin N Am 14 (2002) 477–490 481

before grafting [76]. If the graft is performed before
the expansion of the maxilla, a 3-month period must
elapse before this expansion. If a bilateral cleft exists
with a premaxilla, the maxilla must be expanded first
before distalization of the premaxilla to ensure proper
space. The Quadhelix and Hyrax appliances that are
usually used for maxillary expansion should be left in
place for at least 3 months postoperatively to help
prevent relapse. It is critical that the orthodontic
alignment of the anterior teeth be attempted with great
care to avoid root exposure through the thin alveolar
bone in the cleft region [2].

Fig. 1. Case of a unilateral alveolar cleft. (A,B) A unilateral cleft in the area of the left maxilla. (C,D) Patient 2 weeks after
operation from a secondary alveolar bone grafting procedure (autogenous cancellous bone). (E,F) Patient 3 months after operation.
482 A. Kazemi et al. / Oral Maxillofacial Surg Clin N Am 14 (2002) 477–490
Surgical technique
Three basic surgical principles must be satisfied
for the successful treatment of the alveolar cleft
grafting: (1) closure of oronasal fistula, (2) adequate
volume of graft material, and (3) water tight and
tension-free closure.
The preprocedural considerations by the surgeon
should include the amount of mucosa available for
closure, the best flap design to maintain adequate
blood supply and tension-free closure, the extent of
the oronasal communication, the level of support
needed for the alar base, and the donor site evaluation.
Once these decisions have been made by the surgeon,
he or she can approach the surgery with confidence
and focus on accomplishing individual steps effi-
ciently and completely.
General anesthesia is the most common choice of
anesthesia for the repair of the alveolar cleft, espe-
cially if a donor site is involved. Nasal intubation on
the unaffected side is preferred; however, an oral
endotracheal tube tucked to the opposite side may
be adequate. The presence of a pharyngeal flap should
be determined before intubation. Placement of a throat
pack prevents passage of excess blood into the stom-
ach, which minimizes the chance of postextuba-
tion emesis and possible aspiration. Irrigation of the
oral cavity with chlorhexidine solution is advised to
decrease the chance of immediate postoperative infec-
tion. Injection with local anesthesia with epinephrine
not only aids with postoperative pain control and
intraoperative hemostasis but also allows the surgeon
to identify the margins of the bony cleft and the
oronasal communication. If the graft material allows
for a two-team approach, it is more convenient to
choose the donor site opposite the side of the cleft to
decrease the amount of interference between the two
teams and possible cross-contamination of the donor
site field.
Once the local anesthesia has been applied, an
incision is made through the mucosa overlying the
cleft down to the bony margins to allow the vertical
portion of the cleft to be used for the closure of the
nasal floor. There is usually adequate amount of tissue
present within the oronasal fistula, which leaves one
with enough tissue to achieve an oral closure. The area
of the pyriform aperture creates a unique problem
Fig. 2. The repair of a unilateral alveolar cleft. (A,B) Incision line for an oblique sliding flap (dashed line). (C) The closure of the
nasal mucosa and the introduction of the bone graft to the alveolar defect. (D) Depiction of the nasal mucosa flap along with the
closure of the oral mucosa. (E) Final mucosal closure of the oblique sliding flap. (F) A palatal splint placed over the closure area
to prevent formation of a hematoma and stabilize the bone graft.
because there are no bony margins. In this area, the
soft tissue is divided into two layers to create adequate
tissue for the closure of the most superior and anterior
aspect of the oronasal fistula. A periosteal elevator is
used to elevate the mucosa within the cleft, which
allows for the closure of the oronasal fistula and full
exposure of the bony walls of the cleft. All excess soft
tissue should be trimmed from this area to allow for
maximum contact of native bone with the bone graft.
The ideal position for the inverted suture line and the
knots of the oronasal fistula closure is toward the nasal
side. Once the soft tissue flap design is carried out and
the tissue is elevated, the bone graft material can be
placed in the area of the alveolar cleft and the final
closure initiated (Figs. 1,2).
At this juncture the flap design that was chosen
preoperatively must be implemented. Three main soft
tissue flap designs are described in the literature.
Posnick [21] points out two important factors that
must be considered in choosing a flap design: (1)
preserving the vestibular architecture and (2) provid-
ing the maximum attached mucosa in the area of the
alveolar cleft to allow for development of a normal
periodontal sulcus and attachment of erupting canine.
The buccal finger flap has an excellent blood
supply and provides adequate soft tissue for the
closure over the bone graft. It does not satisfy the
two factors mentioned previously, however. It short-
ens the buccal vestibule and provides nonkeratinized
tissue in the area of eruption of the canine.
The lateral sliding flap is raised on the lesser
segment with a broad base and has an excellent blood
supply. It brings adjacent attached gingiva to the area
of the alveolar cleft. It leads to shortening (although
less) of the buccal vestibule, however. Another nega-
tive factor associated with this type of flap is the
reliance on secondary healing of the mucosa in the
denuded area adjacent to the alveolar cleft. This flap
design provides for an excellent tension-free closure
and decreases the chance of dehiscence.
The oblique sliding flap is a modification of the
Moczair flap. The adjacent attached mucosa from the
lesser and the greater segments are brought to the al-
veolar cleft site, thus covering the newly formed ridge.
It provides more than adequate attached gingival for
tension-free closure of wide alveolar clefts. There is a
minor decrease in the vestibular depth. This same
A. Kazemi et al. / Oral Maxillofacial Surg Clin N Am 14 (2002) 477–490 483
484 A. Kazemi et al. / Oral Maxillofacial Surg Clin N Am 14 (2002) 477–490

Fig. 3. Case of a bilateral alveolar cleft. (A) Preoperative view of the bilateral cleft defect. (B) Postoperative view of the closure
of the oblique sliding flap. (C,D) Two-year and 2-month postoperative palatal and labial view.

approach is carried out with the palatal tissue, and
there may be reliance on healing by secondary inten-
tion at the distal release sites. The four corners of the
flap are closed with a horizontal mattress suture. This
is the authors’ flap of choice (Figs. 3,4).
The palatal flap with posterior release allows for
anterior advancement of the palatal attached mucosa
to the alveolar cleft site. The obvious danger of
damage to the greater palatine neurovascular bundle
detracts from such flap design, however.
With such significant mobilization of the adjacent
mucosa and the placement of the bone graft, it is
advisable to place a palatal splint (fabricated preop-
eratively) to provide maximum immobilization of
the bone graft and support the palatal tissue. The
splint also may play a role in minimizing the forma-
tion of hematoma. Care must be taken to avoid tight
pressure points on the palatal mucosa, because it
creates added postoperative pain and discomfort for
the patient and may decrease the blood flow to the
flap edges (Fig. 5).
In the case of a bilateral alveolar cleft, the tech-
nique is essentially the same, with the precaution that
the premaxilla cannot provide significant tissue for
advancement. The adjacent sites must provide the soft
tissue coverage. The greatest challenge in the closure
of such cases occurs in the area directly posterior to
the premaxilla.
Postoperatively, a liquid diet, avoidance of trauma
to the site, and avoidance of activities such as swim-
ming are recommended for 5 to 7 days (or until the
first postoperative visit). The patient is placed on
antibiotics and nasal decongestants after the operation
and for at least 1 week postoperatively. Meticulous
oral hygiene with chlorhexidine mouth wash rinses is
essential in minimizing the chance of infection. Hos-
pital stays with these procedures depend on the
individual patient, choice of donor site, and other
miscellaneous factors that necessitate further careful
observation of the patient.
Complications of the alveolar cleft grafting with
primary oral and nasal closure can include infection,
 A. Kazemi et al. / Oral Maxillofacial Surg Clin N Am 14 (2002) 477–490 485

Fig. 4. The repair of a bilateral alveolar cleft using an oblique sliding flap technique. (A) A bilateral alveolar cleft palate. (B)
Needle palpation of the bony edges of the alveolar cleft while injecting local anesthesia. (C) The incision line (dashed line). (D)
Elevation of the nasal mucosa on the left and closure of the nasal mucosa on the right. Placement of the bone graft over the closed
nasal mucosa. (E,F) Palatal depiction of the movement of the adjacent mucosa in the oblique sliding flap technique. (G) Mucosal
closure in a bilateral alveolar cleft. (H,I) Final closure of the bilateral alveolar cleft repair using a oblique sliding flap technique.
486 A. Kazemi et al. / Oral Maxillofacial Surg Clin N Am 14 (2002) 477–490

Fig. 4 (continued ).

wound dehiscence, loss of the graft, and incomplete Summary

closure of the oronasal fistula. An infection is the most
detrimental complication that may occur in this sur-
gery. Observance of the following steps can aid in
reducing the rate of infection and avoiding the cre-
ation of a larger defect and a larger oronasal fistula:
1. Preoperative oral hygiene
2. Appropriate intraoperative and postoperative
antibiotics
3. Excellent postoperative oral hygiene
4. Nasal decongestants
5. Prompt recognition and treatment of upper res-
piratory infection.
Although many controversies exist regarding the
timing, choice of graft material, or even flap design,
this procedure has provided a predictable means of
resolving a unique and debilitating problem for the
cleft patient. Considering that these patients are
exposed to numerous surgical procedures, it is the
surgeons’ obligation to plan operations carefully and
provide individualized treatment that allows for the
best results for individual patients.
With the best interest of the cleft patients in mind,
we must strive forward to create better techniques and
materials to repair alveolar clefts. Because this subject

Fig. 5. Clinical presentation of the posterior release palatal advancement technique. (A,B) Labial and palatal view of a palatal
cleft. (C) Reflection of the posterior palatal flap, exposing the palatal cleft. (D) Placement of the autogenous cancellous bone
graft in the area of the palatal defect. (E) Closure of the palatal mucosa overlying the palatal defect. (F) Final closure of the
palatal flap with posterior release. (G) Six-month postoperative view of the palatal flap.
A. Kazemi et al. / Oral Maxillofacial Surg Clin N Am 14 (2002) 477–490 487
488 A. Kazemi et al. / Oral Maxillofacial Surg Clin N Am 14 (2002) 477–490
involves many variables and is not conducive to
prospective and randomized studies, it will take con-
siderable communication and sharing on the parts of
the clinicians involved to advance the science of al-
veolar cleft grafting.
References
[1] Koberg WR. Present view of bone grafting in
cleft palate [review]. J Maxillofac Surg 1973;1:
185 – 93.
[2] Zeitler D. Alveolar cleft grafts. In: Fonseca R, editor.
Oral and maxillofacial surgery. Philadelphia: WB Sa-
unders; 2000. p. 75 – 86.
[3] Jones MC. Facial clefting: etiology and development
pathogenesis. Clin Plast Surg 1993;20:599 – 608.
[4] Vanderas AP. Incidence of cleft lip, cleft palate, and
cleft lip and palate among races: a review. Cleft Palate
J 1987;24:216.
[5] Fraser FC. The genetics of cleft lip and palate. Am J
Hum Genet 1970;22:336 – 52.
[6] Fraser FC. Research revisited: the genetics of cleft lip
and cleft palate. Cleft Palate J 1989;26:255 – 7.
[7] Tolarova M, Cervenka J. Classification and birth
prevalence of orofacial clefts. Am J Med Genet
1998;75: 126 – 37.
[8] Ahmad NN, McDonald-McGinn DM, Zackai EH, et
al. A second mutation in the type II Pro collagen gene
(COL2AI) causing Stickler syndrome (arthroophthal-
moopathy) is also a premature termination codon. Am
J Hum Genet 1993;52:39 – 45.
[9] Brunner HG, van Beersum SE, Warman ML, et al. A
Stickler syndrome gene is linked to chromosome 6
near the COL11A2 gene. Hum Mol Genet 1994;3:
1561 – 4.
[10] Tassabehji M, Newton VE, Leverton K, et al. PAX3
gene structure and mutations: close analogies between
Waardenburg syndrome and the splotch mouse. Hum
Mol Genet 1994;3:1069 – 74.
[11] Belloni E, Muenke M, Roessler E, et al. Identification
of sonic hedgehog as a candidate gene responsible for
holoprosencephaly. Nat Genet 1996;14:353 – 6.
[12] Roessler E, Belloni E, Gaudenz K, et al. Mutations in
the human Sonic Hedgehog gene cause holoprosen-
cephaly. Nat Genet 1996;14:357 – 60.
[13] Vargervik K, Ferrari C. Embryogenesis and compre-
hensive management of the cleft patient. In: Fonseca
R, editor. Oral and maxillofacial surgery. Philadel-
phia: WB Saunders; 2000. p. 3 – 13.
[14] Hwang SJ, Beaty TH, Panny SR, et al. Association
study of transforming growth factor alpha (TGF alpha)
Tag I polymorphism and oral clefts: indication of gene-
environment interaction in a population-based sample
of infants with birth defects. Am J Epidemiol 1995;
141:629 – 36.
[15] Tolarova M, Harris J. Reduced recurrence of orofacial
clefts after periconceptional supplementation with
high-dose folic acid and multivitamins. Teratology
1995;51:71 – 8.
[16] Dravet C, Jutian C, Legras C, et al. Epilepsy, anti-
epileptic drugs and malformations in children of
women with epilepsy: a French prospective cohort
study. Neurology 1992;42(Suppl 5):75 – 82.
[17] Jones KL, Smith DW, Ulleland CN, et al. Pattern of
malformations in offspring of chronic alcoholic moth-
ers. Lancet 1973;1:1267 – 71.
[18] Wyszynski DF, Beaty TH. Review of the role of po-
tential teratogens in the origin of human non-syndrom-
ic oral clefts. Teratology 1996;53:309 – 17.
[19] Stassen L. Alveolar bone grafting: how I do it. In:
Booth P, Schendel S, Hausamen J, editors. Oral and
maxillofacial surgery. New York: Churchill-Living-
stone; 1999. p. 1047 – 57.
[20] Hawkins J. Secondary bone grafting for unilateral
alveolar clefts. Chicago: University of Illinois at Chi-
cago, Grand Rounds; 2000.
[21] Posnick J. The staging of cleft lip and palate recon-
struction: infancy through adolescence. In: Rose A,
Ross A, editors. Craniofacial and Maxillofacial Sur-
gery in Children and Young Adults. Philadelphia: WB
Saunders; 2000. p. 785 – 815.
[22] Freide H, Johanson B. A follow-up study of cleft
children treated with primary bone grafting. Part I:
orthodontic aspects. Scand J Plast Reconstr Surg
1974;8: 88 – 103.
[23] Jolleys A, Robertson NRE. A study of the effects of
early bone grafting in complete clefts of the lip and
palate: 5 year study. Br J Plast Surg 1972;25:229 – 37.
[24] Molsted K, Dahl E, Skovgaard LT, et al. A multi-
centre comparison of treatment regimens for unilat-
eral cleft lip and palate using a multiple regression
model. Scand J Plast Reconstr Surg Hand Surg
1993;27:277 – 84.
[25] Prickrell K, Quinn G, Massengill R. Primary bone
grafting of the maxilla in clefts of the lip and palate.
Plast Reconstr Surg 1968;41:438 – 43.
[26] Pruzansky S. Presurgical orthopedics and bone graft-
ing for infants with cleft lip and palate: a dissent.
Cleft Palate J 1964;1:229 – 37.
[27] Rehrmann AH, Koberg WR, Koch H. Long-term
postoperative results of primary and secondary bone
grafting in complete clefts of lip and palate. Cleft
Palate J 1970;7:206 – 21.
[28] Robertson NRE, Jolleys A. Effects of early bone
grafting in complete clefts of lip and palate. Plast
Reconstr Surg 1968;42:414 – 21.
[29] Rosenstein SW, Monroe CW, Kernahan DA, et al.
The case for early bone grafting in the cleft lip and
palate. Plast Reconstr Surg 1982;70:297 – 307.
[30] Rosenstein SW, Dado DV, Kernahan DA, et al.
The case for early bone grafting in cleft lip and palate:
a second report. Plast Reconstr Surg 1991;87:644 – 54.
[31] Sameshima GT, Banh DS, Smahel Z, et al. Facial
growth after primary periosteoplasy versus primary
bone grafting in unilateral cleft lip and palate. Cleft
Palate Craniofac J 1996;33:300.
 A. Kazemi et al. / Oral Maxillofacial Surg Clin N Am 14 (2002) 477–490
[32] Smahel Z, Mullerova Z, Nejedly A, et al. Changes in
craniofacial development due to modifications of the
treatment of unilateral cleft lip and palate. Cleft Palate
Craniofac J 1998;35:240 – 7.
[33] Smahel Z, Mullerova Z, Horak I. Facial development
in unilateral cleft lip and palate prior to the eruption of
permanent incisors after primary bone grafting and
periosteal flap surgery. Acta Chir Plast 1996;38:30 – 6.
[34] Spyropoulos MN, Linder-Aronson S. Evaluation of
facial features in two groups of cleft lip and palate
patients receiving centralized and non-centralized
treatment regimens. Eur J Orthod 1997;19:411 – 22.
[35] Suzuki A, Goto K, Nakamura N, et al. Cephalometric
comparison of craniofacial morphology between pri-
mary bone grafted and nongrafted complete unilateral
cleft lip and palate adults. Cleft Palate Craniofac J
1996;33:429 – 35.
[36a] Pickrell K, Quinn G, Massengill R. Primary bone
grafting of the maxilla in clefts of the lip and palate.
Plast Reconstr Surg 1968;41:438 – 43.
[36b] Molsted K, Dahl E, Brattstrom V, et al. A six center
international study of treatment outcome in patients
with clefts of the lip and palate: evaluation of maxil-
lary asymmetry. Cleft Palate Craniofac J 1993;30:22.
[37] Keese E, Schmelzle R. New findings concerning early
bone grafting procedures in patients with cleft lip and
palate. J Craniomaxillofac Surg 1995;23: 296 – 301.
[38] Dado DV, Rosenstein SW, Alder ME, et al. Long-
term assessment of early alveolar bone grafts using
three-dimensional computer-assisted tomography: a
pilot study. Plast Reconstr Surg 1997;99:1840 – 5.
[39] Andlin-Sobocki A, Eliasson LA, Paulin G. Periodon-
tal evaluation of teeth in bone grafted regions in pa-
tients with unilateral cleft lip and cleft palate. Am J
Orthodont Dentofacial Orthop 1995;107:144 – 52.
[40] Hall HD, Posnick JC. Early results of secondary bone
grafts in 106 alveolar clefts. J Oral Maxillofac Surg
1983;41:289 – 94.
[41] Jia YL, James DR, Mars M. Bilateral alveolar bone
grafting: a report of 55 consecutively-treated patients.
Eur J Orthod 1998;20:299 – 307.
[42] Kalaaji A, Lilja J, Friede H, et al. Bone grafting in the
mixed and permanent dentition in cleft lip and palate
patients: long-term results and the role of the sur-
geon’s experience. J Craniomaxillofac Surg 1996;
24:29 – 35.
[43] Lee C, Crepeau RJ, Williams HB, et al. Alveolar cleft
bone grafts: results and imprecisions of the dental
radiograph. Plast Reconstr Surg 1995;96:1534 – 8.
[44] Ramstad T, Semb G. The effect of alveolar bone
grafting on the prosthodontic/reconstructive treatment
of patients with unilateral complete cleft lip and plate.
Int J Prosthodont 1997;10:156 – 63.
[45] Troxell JB, Fonseca RJ, Osborn DB. A retrospective
study of alveolar cleft grafting. J Oral Maxillofac
Surg 1982;40:721 – 5.
[46] Clark J, Zeitler DL. Outcome of alveolar grafting in
cleft patients of different ages. J Oral Maxillofac Surg
1996;54(Suppl 3):117.
489
[47] Boyne PJ. Bone grafting in the osseous reconstruction
of alveolar and palatal clefts. Oral Maxillofac Surg
Clin N Am 1991;3:589 – 97.
[48] Posnick JC, Tompson B. Cleft orthognathic surgery:
complications and long-term results. Plast Reconstr
Surg 1995;96:255.
[49] Allard RHB, Lekkas C, Swart JGN. Autologous ver-
sus homologous bone grafting in osteotomies, sec-
ondary cleft repairs and ridge augmentations: a
clinical study. Oral Surg Oral Med Oral Pathol
1987;64:269 – 74.
[50] Ames JR, Ryan DE, Maki KA. The autogenous par-
ticulate cancellous bone marrow graft in alveolar
clefts. J Oral Surg 1981;51:588 – 91.
[51] Canaday JW, Zeitler DL, Thompson SA, et al. Suit-
ability of the iliac crest as a site for harvest of auto-
genous bone grafts. Cleft Palate Craniofac J 1983;30:
579 – 81.
[52] Catone GA, Reimer BL, McNeir D, et al. Tibial au-
togenous cancellous bone as an alternative donor site
in maxillofacial surgery: a preliminary report. J Oral
Maxillofac Surg 1992;50:1258.
[53] Craft PD, Sargent LA. Membranous bone healing and
techniques in calvarial bone grafting. Clin Plast Surg
1989;16:11 – 9.
[54] Feinberg SE, Vitt M. Effect of calcium phosphate
ceramic implants on tooth eruption. J Oral Maxillofac
Surg 1988;46:121 – 7.
[55] Georgiade NC, Pickrell KL, Quinn GW. Varying con-
cepts in bone grafting of alveolar palatal defects. Cleft
Palate J 1964;1:438 – 43.
[56] Harsha BC, Turvey TA, Powers SK. Use of autoge-
nous cranial bone grafts in maxillofacial surgery. J
Oral Maxillofac Surg 1986;44:11 – 5.
[57] Horwell BB, ElDeeb M. Nonporous hydroxyapatite
in the repair of alveolar clefts in a primate model:
clinical and histological findings. J Oral Maxillofac
Surg 1989;47:946 – 52.
[58] Kaban LB, Mulliken JB, Glowacki J. Treatment of
jaw defects with demineralized bone implants. J Oral
Maxillofac Surg 1982;40:623 – 6.
[59] Kartebein MJ, Nelson CL, Sadove AM. Retrospective
analysis of 135 secondary alveolar cleft grafts using
iliac or calvarial bone. J Oral Maxillofac Surg 1991;
49:493 – 8.
[60] Koole R. Ectomesemchymal mandibular symphysis
bone graft: an improvement in alveolar cleft grafting.
Cleft Palate Craniofac J 1994;31:217.
[61] Kraut RA. The use of allogenic bone for alveolar cleft
grafting. J Oral Surg 1987;64:278 – 82.
[62] Kusiak JF, Zins JE, Whitaker LA. The early revascu-
larization of membranous bone. Plast Reconstr Surg
1985;76:510 – 6.
[63] LaRossa D, Buchman S, Rothkopf DM, et al. A com-
parison of iliac and cranial bone in secondary graft-
ing of alveolar clefts. Plast Reconstr Surg 1995;96:
789 – 99.
[64] Marx RE, Miller RI, Ehler WJ, et al. A comparison of
particulate allogenic and particulate autogenous bone
490 A. Kazemi et al. / Oral Maxillofacial Surg Clin N Am 14 (2002) 477–490
grafts in maxillary alveolar clefts in dogs. J Oral
Maxillofac Surg 1984;42:3 – 9.
[65] Matthews DE, Broomhead I, Grossman W, et al.
Early and late bone grafting in cases of cleft lip and
palate. Br J Plast Surg 1970;23:115 – 29.
[66] Nique T, Fonseca RJ, Upton LG, et al. Particulate
allogenic bone grafts into maxillary alveolar clefts
in humans. J Oral Maxillofac Surg 1987;45:386 – 92.
[67] Rudman RA. Prospective evaluation of morbidity as-
sociated with iliac crest harvest for alveolar cleft
grafting. J Oral Maxillofac Surg 1997;55:219 – 23.
[68] Sadove AM, Nelson CL, Eppley BL, et al. An eval-
uation of calvarial and iliac donor sites in alveolar
cleft grafting. Cleft Palate J 1990;17:225 – 9.
[69] Sindet-Pedersen S, Enemark H. Reconstruction of al-
veolar clefts with mandibular or iliac crest bone
grafts: a comparative study. J Oral Maxillofac Surg
1990;48: 554 – 8.
[70] Sindet-Pedersen S, Enemark H. Mandibular bone
grafts for reconstruction of alveolar clefts. J Oral
Maxillofac Surg 1988;46:533 – 7.
[71] Smith JD, Aramson M. Membranous versus endo-
chondral bone autografts. Arch Otolaryngol
1974;99: 203 – 5.
[72] So LL, Lui WW. Alternative donor site for alveolar
bone grafting in adults with cleft lip and palate. Angle
Orthod 1996;66:9 – 16.
[73] Tan AES, Brogan WF, McComb HK, et al. Secondary
alveolar bone grafting: 5 year periodontal and radio-
graphic evaluation in 100 consecutive cases. Cleft
Palate Craniofac J 1996;33:513.
[74] Wolfe SA, Berkowitz S. The use of cranial bone
grafts in the closure of alveolar and anterior palatal
clefts. Plast Reconstr Surg 1983;72:659 – 71.
[75] Zins JE, Whitaker LA. Membranous versus endo-
chondral bone: implications for craniofacial recon-
struction. Plast Reconstr Surg 1983;72:778 – 84.
[76] Boyne PJ, Sands NR. Combined orthodontic-surgical
management of residual palato-alveolar cleft defects.
Am J Orthod 1976;70:20 – 37.
[77] Moore RN. Orthodontic management of the patient
with cleft lip and palate. Ear Nose Throat J 1986;65:
356 – 7.
[78] Shaw WC, Semb G. Current approaches to the ortho-
dontic management of cleft lip and palate. J R Soc
Med 1990;83:30 – 3.
[79] Lexer E. Die verwendung der freien knochenplastik
nebst versuchen über gelenkversteifung und gelenkt-
vansplantation. Langenbecks Arch Chir 1908;86:939.
[80] Drachter R. Die gaumenspalte und deren operative
behandlay. Dtsch Z Chir 1914;131:1.
[81] Veau V. Division palatine; anatomic Chirurgie, pho-
netique. Paris: Masson; 1931.
[82] Boyne PJ, Sands NR. Secondary bone grafting of
residual alveolar and palatal clefts. J Oral Surg
1972;30: 87 – 92.