Prevalence of Dental Anomalies in Nonsyndromic Individuals With Cleft Lip

and Palate: A Systematic Review and Meta-analysis

Patricia Nivoloni Tannure, D.D.S., M.S.D., Cristiana Aroeira G.R. Oliveira, D.D.S., M.S.D., Lucianne Cople Maia,
D.D.S., M.S.D., Ph.D., Alexandre R. Vieira, D.D.S., M.S., Ph.D., Jose Mauro Granjeiro, D.D.S., M.Sc., Ph.D.,
Marcelo de Castro Costa, D.D.S., Ph.D.
Objective: To assess whether individuals born with nonsyndromic oral clefts
display a higher frequency of dental anomalies.
Design: A search of MEDLINE, BIREME, OVID ALL EMB Reviews, and The
Cochrane Library was conducted. The methodologic quality of the papers
selected was assessed and scored. Papers reporting observational controlled
studies of nonsyndromic forms of oral cleft matched for dental anomalies in
primary and/or permanent teeth were included without language restrictions.
Eligible studies were scored as Alow risk of bias, Bmoderate risk of
bias, or Chigh risk of bias and poor quality. Fixed and random effects
models were used to aggregate individual odds ratios (OR) and to derive
pooled estimates and 95% confidence intervals.
Results: Six studies fulfilled our selection criteria and were included in the
meta-analysis. Three distinct subgroup analyses were carried out in terms of
dental anomalies. In the tooth agenesis meta-analysis, a random effects model
was used because of heterogeneity and showed a significant association
between tooth agenesis and oral clefts (OR = 12.31; 95% confidence interval
[CI] = 3.75 to 40.36). In the remaining analyses, the fixed effects model revealed
a positive association between supernumerary (OR = 4.99; 95% CI, 2.58 to 9.64)
and crown morphologic abnormalities (OR = 5.69; 95% CI, 3.96 to 8.19) with
oral clefts. Most included studies were of low to moderate quality.
Conclusion: Although general limitations in study design were observed, the
evidence suggests that a higher number of dental anomalies in the permanent
dentition are noted in individuals born with oral clefts.
KEY WORDS: cleft lip, cleft lip and/or palate, cleft palate, meta-analysis, tooth
abnormalities

Cleft lip and palate constitutes approximately 65% of

malformations affecting the head and neck (Owens et al.,
1985). It represents a complex phenotype and reflects a
breakdown in the normal mechanisms involved during
early embryologic development of the face (Cobourne,
2004). The origin of oral clefts is thought to be
multifactorial, with both genetic and environmental factors
playing a role (Murray, 2002). The incidence of these

defects varies according to geographic location, ethnicity,

and socioeconomic status, affecting 1 in every 500 to 1000
births worldwide (Murray, 2002; Cox, 2004).
The occurrence of cleft lip and palate and the development
of tooth germs have a close embryologic relationship in terms
of timing and anatomic position (Stahl et al., 2006). It is
suggested that cleft genes produce disturbances in many body
tissues and therefore also affect the dental lamina (Johnson,
1967). It has been reported that individuals born with clefts
have a higher incidence of abnormal crown morphology,
hypodontia, supernumerary teeth, and taurodontism
(Schroeder and Green, 1975; Poyry and Ranta, 1985; Dahllof
et al., 1989; Shapira et al., 2000; Dewinter et al., 2003; Ribeiro
et al., 2003; Letra et al., 2007; Menezes and Vieira, 2008;
Kuchler et al., 2010). In addition, previous reports have
related higher frequencies of dental anomalies as the severity
of the cleft increases (Eerens et al., 2001; Slayton et al., 2003;
Aizenbud et al., 2005). Studies have indicated that dental
anomalies may represent an additional clinical marker for
oral clefts, suggesting that isolated cleft lip and palate can be
subphenotyped on the basis of dental development (Letra
et al., 2007; Menezes and Vieira, 2008).

Drs. Tannure, Oliveira, Maia, and de Castro Costa are members,

Department of Pediatric Dentistry and Orthodontics, School of Dentistry,
Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. Dr. Vieira is
a member of Departments of Oral Biology and Pediatric Dentistry and
Center of Dental and Craniofacial Genetics, School of Dental Medicine,
University of Pittsburgh, Pittsburgh, Pennsylvania. Dr. Granjeiro is a
member of Department of Cell and Molecular Biology and Cell Therapy
Center, Fluminense Federal University, Rio de Janeiro, Brazil.
Submitted February 2010; Accepted February 2011.
Address correspondence to: Dr. Patricia Nivoloni Tannure, Federal
University of Rio de Janeiro, Pediatric Dentistry and Orthodontics, Rua
Prof. Rodolpho Paulo Rocco, 325 Rio de Janeiro, Rio de Janeiro 21941913 Brazil. E-mail pntannure@gmail.com.
DOI: 10.1597/10-043
194

Tannure et al., DENTAL ANOMALIES IN INDIVIDUALS WITH ORAL CLEFTS

More recent studies confirm the evidence that common

genetic factors may contribute to both oral clefts and dental
anomalies (van den Boogaard et al., 2000; Slayton et al.,
2003; Vieira, 2003; Vieira et al., 2008). It is well
documented that teeth close to the cleft are likely to have
malformations or to be missing (Ranta, 1986; Rawashdeh
and Abu Sirdaneh, 2009). Less information is available
regarding dental anomalies outside the cleft area. The aim
of this study was to undertake a systematic review and
meta-analysis to assess the evidence that individuals with
isolated oral clefts may display higher frequencies of dental
anomalies.
MATERIALS AND METHODS

195

score of 1 point. Only one was assigned a score of 3 points

because it evaluated the distribution of dental anomalies
according to the region or according to the arch segment/
class of teeth, making 9 the maximum score possible.
After this, researchers classified the studies into three
categories with scores A to C according to predetermined criteria for method and performance. To obtain
score A, low risk of bias, the study should present 8 to
9 points in the methodologic scoring system; to obtain
score B, moderate risk of bias, the study should present 5
to 7 points; and to obtain score C, high risk of bias and
poor quality, it should present 1 to 4 points. Studies
assigned the higher scores (A and B) were weighed
more heavily when the meta-analysis was performed.

Search Strategy

Meta-analysis

Publications of potential relevance to our study were

identified by using both exploded MeSH headings and text
words in a search of MEDLINE (19662009), BIREME
(19672009), OVID ALL EMB Reviews (19502009), and
The Cochrane Library. In these databases, the terms were
cleft lip [MeSH terms] OR cleft palate [MeSH terms]
OR cleft lip and/or palate [tw] OR oral clefts [tw]
AND dental anomalies [tw] OR tooth abnormalities
[MeSH terms] OR anodontia [MeSH terms] OR
agenesis [MeSH terms] OR tooth, supernumerary
[MeSH terms] OR microdontia [tw] OR tooth malposition [tw] OR tooth, impacted [MeSH terms] OR
tooth malformation [tw] OR tooth transposition [tw]
OR tooth rotation [tw] OR taurodontism [tw].
Additional articles of potential relevance were identified
by manual searches. Observational controlled study designs
composed of nonsyndromic forms of oral clefts matched
for dental anomalies in primary and/or permanent teeth
were included without language restrictions.
Textbooks, dissertations, case reports, case series, review
articles, and abstracts were excluded. Two examiners
(P.N.T. and C.A.G.R.O.) independently screened each
paper by examining the title, abstract, and keywords. If
examiners had diverging opinions, the papers were reexamined until a consensus was reached. If relevant data
were missing, the authors of the papers in question were
contacted for additional information.

The meta-analysis was performed by the software RevMan, version 5.0, provided by The Cochrane Collaboration
(http://ims.cochrane.org/revman/download). The OR was
used as a measure of effect with its 95% CI between oral
cleft and risk of dental anomalies. Heterogeneity between
studies was assessed using a standard chi-square test. If
homogeneity existed among the studies (p $ .10), the fixed
effects model (Peto method) was applied to aggregate the
data. If homogeneity was rejected (p , .10), a random
effects model (M-H method) was the option.

Quality Assessment of Studies

We performed a quality assessment of the remaining
studies to control for influence bias, to gain insight into
potential comparisons, and to guide interpretation of
findings (Higgins and Green, 2005). Selected articles were
assessed in accordance with the modified criteria of Loney
et al. (1998). Seven criteria were analyzed, and a methodologic scoring system was used to rate the quality of the
papers. The authors recommended weights for each item
for the scoring system. Thus six criteria were assigned a

RESULTS
Search queries retrieved a total of 505 papers: 253
references from MEDLINE, 203 references from the
BIREME database, 34 articles from the OVID ALL
EMB Reviews database, and 15 papers from The Cochrane
Library database. Seventeen studies appearing in two
database searches were considered only once. Studies were
excluded from this review for two reasons (Fig. 1). Most of
the excluded studies (n 5 480) did not include frequency
data for clefts and dental anomalies and were not
observational and controlled in design. Two studies that
included individuals with oral clefts and additional
structural abnormalities or defined syndromes (Dahllof et
al., 1989; Budai et al., 2001) were excluded. Eight studies
were analyzed and are displayed in Table 1. A total of six
studies fulfilled all criteria and were carefully read and
ranked as shown in Table 2. Four studies selected for final
assessment were graded with the score B, and the other
two were graded with the score C.
The six eligible studies were selected for the metaanalysis. Three distinct subgroup analyses were carried out
in terms of dental anomalies. For tooth agenesis, data from
Jordan et al. (1966), Schroeder and Green (1975), Quezada
et al. (1988), Eerens et al. (2001), and Letra et al. (2007)
were included. For supernumerary teeth, data from Jordan
et al. (1966), Schroeder and Green (1975), and Letra et al.
(2007) were included. For morphologic irregularities of the

196

Cleft PalateCraniofacial Journal, March 2012, Vol. 49 No. 2

crown, data from Jordan et al. (1966), Schroeder and Green

(1975), Letra et al. (2007), and Rawashdeh and Abu
Sirdaneh (2009) were included. Because Rawashdeh and
Abu Sirdaneh (2009) reported data by total number of
teeth, we estimated the number of individuals affected for
inclusion in the meta-analysis. The frequency of morphologic irregularities of the crown was estimated, on the basis
of data from Jordan et al. (1966), Schroeder and Green
(1975), and Letra et al. (2007), as 10.0% for the control
group (n 5 6). The cleft group presented approximately a
seven times greater chance to be affected, based on the
number of affected teeth reported by Rawashdeh and Abu
Sirdaneh (2009); we estimated that 42 individuals born with
clefts had morphologic irregularities of the crown. Only one
study (Quezada et al., 1988) reported separate results by
dentition (permanent or primary), but no data were
available regarding the primary dentition in any other
studies, and only data on the permanent dentition were
included in the analysis.
Heterogeneity tests showed that heterogeneity existed in
the included studies for assessment of tooth agenesis (p ,
.0001), and a random effect was used. The same test for
heterogeneity did not give a significant result (p . .10) for
supernumerary teeth and morphologic irregularities of the
crown; a fixed effects model was therefore used.
In the tooth agenesis subgroup, a significant association
between clefts and tooth agenesis (OR 5 12.31; 95% CI,
3.75 to 40.36) (Fig. 2) was found. The remaining analyses
showed an association between clefts and supernumerary
teeth (OR 5 4.99; 95% CI, 2.58 to 9.64) (Fig. 3) and
morphologic irregularities of the crown (OR 5 5.69; 95%
CI, 3.96 to 8.19) (Fig. 4).
Additionally, we performed a sensitivity analysis by
removing data to evaluate the influence of individual
studies. Heterogeneity in the tooth agenesis analysis was
not resolved by excluding any individual study. Nevertheless, upon exclusion of a specific study (Quezada et al.,
1988), a smaller confidence interval was observed (OR 5
7.54; 95% CI, 2.71 to 20.99). The summary odds ratio was
not significantly changed.
DISCUSSION
Comparison of outcomes from prevalence studies conducted in different populations may allow inferences to be
drawn about the association between a certain disease and
its possible associated factors. These significant inferences
should be drawn from high-quality prevalence research. We
incorporated existing published criteria on disease prevalence (Loney et al., 1998) and developed critical appraisal
criteria to estimate the prevalence of dental anomalies in a
definite population (Table 1).
The most striking finding when this systematic review
was conducted was the high number of papers that were
excluded because of lack of a control group. Moreover, a
majority of publications did not analyze separately

anomalies inside and outside the cleft region. Given that

the cleft region has a bone defect, teeth close to the cleft are
commonly malformed or missing (Ranta, 1986; Rawashdeh
and Abu Sirdaneh, 2009). For this reason, we decided to
attribute higher scores to studies in which authors
presented data on dental anomalies by tooth type, arch
affected, or location inside versus outside the cleft region.
Nevertheless, we are conscious that our meta-analysis
presented particular challenges because of differences in
study design. Combining data on dental anomalies in the
cleft region with those outside the cleft region resulted in
the risk of depriving representation of some studies. To
reduce potential bias, we carried out three specific
subgroup meta-analyses of only relevant and appropriate
data. Moreover, to investigate the individual contribution
of each study to heterogeneity, we excluded each study
from the analysis consecutively and observed only small
effects on the results.
Of the eight case-control studies previously selected, two
were excluded because of the presence of syndromic
patients (Dahllof et al., 1989; Budai et al., 2001). Of a
total of six eligible studies, four were considered to have
moderate risk of bias (Quezada et al., 1988; Eerens et al.,
2001; Letra et al., 2007; Rawashdeh and Abu Sirdaneh,
2009), and two were classified as having a high risk of bias
(Jordan et al., 1966; Shroeder and Green, 1975). Also, when
these six studies were considered, it was noted that in four
of them, the authors showed results according to the region
of anomalies or tooth/arch affected.
Quezada et al. (1988) presented the results according to
the arch affected in the permanent dentition. The authors
concluded that dental anomalies are predominantly confined to the upper jaw of cleft lip and palate patients,
indicating a relationship between cleft formation and
formation of the teeth. On the other hand, Eerens et al.
(2001) reported that just dental anomalies outside the cleft
region were observed, but the authors excluded only the
lateral incisor in the upper jaw on the cleft side. Letra et al.
(2007) did not include dental anomalies inside the cleft
region (affecting maxillary central incisors, lateral incisors,
or canines), because the absence of such teeth was likely the
consequence of developmental anomalies at the cleft side.
Rawashdeh and Abu Sirdaneh (2009) showed results
according to arch and class of teeth.
In terms of the quality of eligible studies, several points
deserve emphasis. The design of the selected studies did not
include sample size calculations or a representative
sampling of the population. Most studies were conducted
in dental schools, and samples of convenience were
obtained in these cases. With respect to matching cases and
controls, most studies (n 5 5) were considered satisfactory
because cases and controls were matched for age and
ethnicity. Despite the fact that one of these studies (Letra et
al., 2007) did not match age in the two groups, it involved a
large sample of 1000 participants, and significant differences were observed in the frequency of tooth agenesis,

USA

USA

Netherlands

Sweden

Hungarian

Belgium

Schroeder,
1975*

Quezada,
1988{

Dahllof,
1989{

Budai,
2001{

Eerens,
2001*

Country

Age,
ethnicity

Sex; age;
ethnicity

Sex; age;
ethnicity

Age,
ethnicity

Ethnicity

Ethnicity

Matched

Convenience

Convenience

Convenience

Convenience

Convenience

Convenience

Sample
Selection

11 years 11 months
(cases) and 13 years
1 month (controls)

Cases and controls

ranged from
1012 years

5.5 years cases and

controls

Outside cleft region 8 years 11 months

(cases) and 9 years
(excluding the
10 months
lateral incisor in
(controls)
the upper jaw on
the cleft side)

Not described

Not described

Cleft
Group

Control
Group

Examiner
Calibration

49

31

250

31

54

38

100

49

94

56

Method

Supernumerary
teeth; tooth
agenesis;
morphologic
irregularities of
the crown
(10 traits)
Supernumerary
teeth; tooth
agenesis;
morphologic
irregularities of
the crown

Dental casts,
radiographs,
and medical and
dental histories

Fetuses and dental

Supernumerary
casts (models)
teeth; tooth
agenesis;
morphologic
irregularities of the
crown (13 traits)

Type of Dental
Anomalies

A statistically highly
significant difference
was noted between
individuals born with or
without clefts in terms
of the number of dental
abnormalities.
This study demonstrated
an increased incidence
of dental trait anomalies
in individuals born with
clefts.

Relevant Findings

No

Dental casts,
radiographs. and
family history

An increased number of
dental anomalies were
found in individuals
born with clefts. These
anomalies are
predominantly confined
to the upper jaw,
irrespective of their
genetic predisposition
and the severity of the
cleft.
Clinical examination Children born with clefts
No
Hypoplasia;
exhibited an increased
hypomineralization; and bite-wing
frequency of enamel
radiographs
supernumerary
hypomineralization,
teeth; tooth
supernumerary teeth,
agenesis; crowding
and crowding.
Clinical examination, Congenitally missing teeth
No
Supernumerary
were more common and
radiographs, and
teeth; tooth
supernumerary teeth
dental casts
agenesis
less common in children
born with cleft palate.
Orthopantomogram Individuals born with
Intra: 0.991; Tooth agenesis;
Inter: 0.994
asymmetric dental and records
clefts and their siblings
development
showed a significantly
higher occurrence of
tooth agenesis and
asymmetric dental
development than
individuals born
without clefts.

No

Fetuses: 800; No
Fetuses (1040 weeks) Fetuses:10;
models: 105 models: 87
and cases and
controls ranged
from 312 years

Mean Age

6.5 years (cases)

Distribution
and 8.75 years
according to arch
(controls)
and dentition

Not described

Not described

Distribution of the
Dental Anomalies
Observed

Overview of the Eight Case-Control Papers Analyzed

Jordan,
1966

First
Author,
Year

TABLE 1

Tannure et al., DENTAL ANOMALIES IN INDIVIDUALS WITH ORAL CLEFTS

197

100
13.4 years (cases) and
Distribution
14.6 years (controls)
according to arch
and class of teeth

No

FIGURE 1 Diagram of literature search and selection process.

* A cleft group with siblings and a nonsibling control group were included in the sample.
{ The cleft group consisted of patients with familial and sporadic cleft lip and palate.
{ Syndromic individuals were included in the cleft group.

Rawashdeh, Jordan
2009

Age,
ethnicity

Convenience

60

500
500
Ethnicity
Brazil
Letra,
2007

Matched
Country

Convenience

Outside cleft region 17.3 years (cases)

and 36.8 years
(excluding the
(controls)
central incisors,
lateral incisors,
and canines in the
upper jaw on the
cleft side)

No

Method
Type of Dental
Anomalies
Examiner
Calibration
Control
Group
Cleft
Group
Mean Age
Distribution of the
Dental Anomalies
Observed
Sample
Selection
First
Author,
Year

Continued
TABLE 1

Clinical examination, Individuals born with

Tooth agenesis;
clefts presented
radiographs, and
microdontia;
considerably more
medical records
supernumerary
dental anomalies than
teeth; malposition;
did control individuals,
impaction;
suggesting a common
malformation;
genetic contribution to
transposition
these two defects.
Dental casts
A significant increase was
Morphologic
noted in the frequency
irregularities of the
of crown morphologic
crown (11 traits)
abnormalities in
individuals born with
clefts, more frequently
peg-shaped maxillary
incisors and missing
hypocone.

Cleft PalateCraniofacial Journal, March 2012, Vol. 49 No. 2

Relevant Findings

198

microdontia, supernumerary teeth, tooth malposition,

impaction, and multiple dental anomalies between individuals with cleft status and control individuals. The other
eligible studies had more modest sample sizes. Critical
appraisal of the published data, evaluating the sample size
required to answer the research question, is an important
step in interpreting the relevance of these results (Noordzij
et al., 2010). A large sample size produces narrow
confidence limits; this is undoubtedly important if the
prevalence or incidence of a given condition is low. Small
sample sizes produce large confidence intervals, making the
findings less precise (Loney et al., 1998). Despite the limited
number of cleft children, the results of Eerens et al. (2001),
for example, revealed that the cleft group showed
significantly more hypodontia when compared with the
nonsibling control group.
Quezada et al. (1988) evaluated morphologic dental
anomalies, hypodontia, and supernumerary teeth in patients with and without cleft lip and palate. Family history,
dental casts, and radiographs were studied. Based on the
occurrence of cleft lip and palate in the family, a distinction
was made between familial and sporadic cleft lip and
palate. Hypodontia was the only dental trait observed
through radiographs/records and compared between cleft
and control groups in the study by Eerens et al. (2001). In
this study, the term hypodontia was used to indicate one or
more missing teeth. Letra et al. (2007) observed the
frequency of tooth agenesis, microdontia, supernumerary
teeth, malposition, impaction, malformation, transposition,
and the combination of more than one dental anomaly, and
compared their frequency in healthy individuals and in
individuals born with a cleft. Clinical examination,
radiographs, and medical records were used as assessment
methods. The term agenesis was used to mean hypodontia
and oligodontia. Radiographs including orthopantomograms were used in three studies ranked with a score of B
(Quezada et al., 1988; Eerens et al., 2001; Letra et al., 2007).
Intraexaminer reproducibility was reported only in the
study by Eerens et al. (2001). Letra et al. (2007) had only

Tannure et al., DENTAL ANOMALIES IN INDIVIDUALS WITH ORAL CLEFTS

TABLE 2

Quality Assessment of Eligible Studies (n = 6) in Accordance With the Modified Criteria of Loney et al. (1998)

Whole population or representative sample selection of the population

by calculating sample size
An appropriate sampling frame or method of subject recruitment
Matching of the controls concerning age and/or gender and/or ethnicity
or at least similar groups for comparison
Objective, suitable, and standard criteria used for measurement of
dental anomalies, such as clinical examination, radiographs, dental
records, and dental casts
Distribution of dental anomalies according to region (inside or
outside cleft region) or according to arch segment/class of teeth
Standardized assessment methods by assessors or interviewers,
including interobserver and/or intraobserver reliability
Data that favored statistical analysis such as chi-square test, relative
risk (RR), risk difference (RD), odds ratio (OD), and multivariate
regression
Total of points
Final Score

199

Methodologic
Scoring System

Jordan,
1966

Schroeder, Quezada,
1975
1988

Eerens,
2001

Letra,
2007

Rawashdeh,
2009

1 point

1 point
1 point

0
1

0
1

0
1

0
1

0
1

0
1

1 point

3 points

1 point

1 point

Maximum score:
9 points

FIGURE 2 Forest plot between cleft and control groups showing the prevalence of tooth agenesis.

FIGURE 3 Forest plot between cleft and control groups showing the prevalence of supernumerary teeth.

FIGURE 4 Forest plot between cleft and control groups showing the prevalence of morphologic irregularities of the crown.

200

Cleft PalateCraniofacial Journal, March 2012, Vol. 49 No. 2

one examiner. On the other hand, Rawashdeh and Abu

Sirdaneh (2009) identified crown morphologic abnormalities only by dental casts.
Letra et al. (2007) reported that children 8 years of age or
younger were excluded from the analysis, mainly because
sometimes premolar tooth buds are not visible on
radiographs at younger ages. Third molars, which are the
teeth most frequently absent in all populations (Graber,
1978; Larmour et al., 2005), were not included in the
evaluation of tooth agenesis because of the age range of
study participants. Eerens et al. (2001) considered congenitally missing teeth if they were absent on the radiograph.
However, the mean age of cleft and control groups was
between 8 and 10 years. The definition of second premolar
agenesis may have introduced bias. On the other hand, the
authors did not report whether third molars were excluded,
but we believe that these teeth were not evaluated because
investigators included young children in both groups.
CONCLUSION
In summary, in spite of the limitations of studies available
in the literature, evidence suggests that individuals born with
clefts have more dental anomalies in the permanent dentition
than unaffected individuals. This meta-analysis has highlighted the need for more carefully designed studies to
analyze individuals with oral cleft with regard to the presence
of dental anomalies and possible common causes.
Acknowledgments. We thank CAPES (Coordenacao de Aperfeicoamento de Pessoal de Nvel Superior) for financial support.

REFERENCES
Aizenbud D, Camasuvi S, Peled M, Brin I. Congenitally missing teeth in
the Israeli cleft population. Cleft Palate Craniofac J. 2005;42:314317.
Budai M, Kocsis SG, Kokai E, Sagi I, Mari A. [Caries, gingivitis and
dental abnormalities in patients with cleft lip and palate]. Fogorv Sz.
2001;94:197199.
Cobourne MT. The complex genetics of cleft lip and palate. Eur J Orthod.
2004;26:716.
Cox TC. Taking it to the max: the genetic and developmental mechanisms
coordinating midfacial morphogenesis and dysmorphology. Clin
Genet. 2004;65:163176.
Dahllof G, Ussisoo-Joandi R, Ideberg M, Modeer T. Caries, gingivitis,
and dental abnormalities in preschool children with cleft lip and/or
palate. Cleft Palate J. 1989;26:233237; discussion 237238.
Dewinter G, Quirynen M, Heidbuchel K, Verdonck A, Willems G, Carels
C. Dental abnormalities, bone graft quality, and periodontal conditions in patients with unilateral cleft lip and palate at different phases
of orthodontic treatment. Cleft Palate Craniofac J. 2003;40:343350.
Eerens K, Vlietinck R, Heidbuchel K, Van Olmen A, Derom C, Willems
G, Carels C. Hypodontia and tooth formation in groups of children
with cleft, siblings without cleft, and nonrelated controls. Cleft Palate
Craniofac J. 2001;38:374378.
Graber LW. Congenital absence of teeth: a review with emphasis on
inheritance patterns. J Am Dent Assoc. 1978;96:266275.

Higgins JPT, Green S. Cochrane Handbook for Systematic Reviews of

Interventions. Version 4.2.4. [Updated March 2005.] Chichester, United
Kingdom: John Wiley & Sons, 2005.
Johnson DB. Some observations on certain developmental dento-alveolar
anomalies and the stigmata of cleft. Dent Pract Dent Rec. 1967;17:
435443.
Jordan RE, Kraus BS, Neptune CM. Dental abnormalities associated
with cleft lip and/or palate. Cleft Palate J. 1966;3:2255.
Kuchler EC, Motta K, Vieira AR, Granjeiro JM. Side of dental anomalies
and taurodontism as potential clinical markers for cleft subphenotypes.
Cleft Palate Craniofac J. 2011;48:103108.
Larmour CJ, Mossey PA, Thind BS, Forgie AH, Stirrups DR.
Hypodontiaa retrospective review of prevalence and etiology. Part
I. Quintessence Int. 2005;36:263270.
Letra A, Menezes R, Granjeiro JM, Vieira AR. Defining subphenotypes
for oral clefts based on dental development. J Dent Res. 2007;86:
986991.
Loney PL, Chambers LW, Bennett KJ, Roberts JG, Stratford PW.
Critical appraisal of the health research literature: prevalence or
incidence of a health problem. Chronic Dis Can. 1998;19:170176.
Menezes R, Vieira AR. Dental anomalies as part of the cleft spectrum.
Cleft Palate Craniofac J. 2008;45:414419.
Murray JC. Gene/environment causes of cleft lip and/or palate. Clin
Genet. 2002;61:248256.
Noordzij M, Tripepi G, Dekker FW, Zoccali C, Tanck MW, Jager KJ.
Sample size calculations: basic principles and common pitfalls. Nephrol
Dial Transplant. 2010;25:13881393.
Owens JR, Jones JW, Harris F. Epidemiology of facial clefting. Arch Dis
Child. 1985;60:521524.
Poyry M, Ranta R. Anomalies in the deciduous dentition outside the cleft
region in children with oral clefts. Proc Finn Dent Soc. 1985;81:9197.
Quezada MGC, Hoeksma JB, van de Velde JP, Prahl-Andersen B,
Kuijpers-Jagtman AM. Dental anomalies in patients with familial and
sporadic cleft lip and palate. J Biol Buccale. 1988;16:185190.
Ranta R. A review of tooth formation in children with cleft lip/palate.
Am J Orthod Dentofacial Orthop. 1986;90:1118.
Rawashdeh MA, Abu Sirdaneh EO. Crown morphologic abnormalities in
the permanent: dentition of patients with cleft lip and palate.
J Craniofac Surg. 2009;20:465470.
Ribeiro LL, Teixeira Das Neves L, Costa B, Ribeiro Gomide M. Dental
anomalies of the permanent lateral incisors and prevalence of
hypodontia outside the cleft area in complete unilateral cleft lip and
palate. Cleft Palate Craniofac J. 2003;40:172175.
Schroeder DC, Green LJ. Frequency of dental trait anomalies in cleft,
sibling, and noncleft groups. J Dent Res. 1975;54:802807.
Shapira Y, Lubit E, Kuftinec MM. Hypodontia in children with various
types of clefts. Angle Orthod. 2000;70:1621.
Slayton RL, Williams L, Murray JC, Wheeler JJ, Lidral AC, Nishimura
CJ. Genetic association studies of cleft lip and/or palate with
hypodontia outside the cleft region. Cleft Palate Craniofac J. 2003;40:
274279.
Stahl F, Grabowski R, Wigger K. Epidemiology of Hoffmeisters
genetically determined predisposition to disturbed development of
the dentition in patients with cleft lip and palate. Cleft Palate
Craniofac J. 2006;43:457465.
van den Boogaard MJ, Dorland M, Beemer FA, van Amstel HK. MSX1
mutation is associated with orofacial clefting and tooth agenesis in
humans. Nat Genet. 2000;24:342343.
Vieira AR. Oral clefts and syndromic forms of tooth agenesis as models
for genetics of isolated tooth agenesis. J Dent Res. 2003;82:162165.
Vieira AR, McHenry TG, Daack-Hirsch S, Murray JC, Marazita ML. A
genome wide linkage scan for cleft lip and palate and dental anomalies.
Am J Med Genet A. 2008;146:14061413.