Prevalence of Dental Anomalies in Nonsyndromic Individuals with Cleft Lip and Palate: A Systematic Review and Meta-analysis

Abstract

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 “A”—low risk of bias, “B”—moderate risk of bias, or “C”—high 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.

Keywords

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 embryologie 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; Küchler 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).

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

Search Strategy

Publications of potential relevance to our study were identified by using both exploded MeSH headings and text words in a search of MEDLINE (1966–2009), BIREME (1967–2009), OVID ALL EMB Reviews (1950–2009), 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 re-examined until a consensus was reached. If relevant data were missing, the authors of the papers in question were contacted for additional information.

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 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.

Meta-analysis

The meta-analysis was performed by the software Rev-Man, 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.

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 = 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.”

Figure 1

Diagram of literature search and selection process.

Table 1

Overview of the Eight Case-Control Papers Analyzed

First Author, Year	Country	Matched	Sample Selection	Distribution of the Dental Anomalies Observed	Mean Age	Cleft Group	Control Group	Examiner Calibration	Type of Dental Anomalies	Method	Relevant Findings
Jordan, 1966	USA	Ethnicity	Convenience	Not described	Fetuses (10–40 weeks) and cases and controls ranged from 3–12 years	Fetuses: 10; models: 105	Fetuses: 800; models: 87	No	Supernumerary teeth; tooth agenesis; morphologic irregularities of the crown (13 traits)	Fetuses and dental casts (models)	A statistically highly significant difference was noted between individuals born with or without clefts in terms of the number of dental abnormalities.
Schroeder, 1975^*	USA	Ethnicity	Convenience	Not described	11 years 11 months (cases) and 13 years 1 month (controls)	56	94	No	Supernumerary teeth; tooth agenesis; morphologic irregularities of the crown (10 traits)	Dental casts, radiographs, and medical and dental histories	This study demonstrated an increased incidence of dental trait anomalies in individuals born with clefts.
Quezada, 1988^†	Netherlands	Age, ethnicity	Convenience	Distribution according to arch and dentition	6.5 years (cases) and 8.75 years (controls)	100	38	No	Supernumerary teeth; tooth agenesis; morphologic irregularities of the crown	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.
Dahllof 1989^‡	Sweden	Sex; age; ethnicity	Convenience	Not described	5.5 years cases and controls	49	49	No	Hypoplasia; hypomineralization; supernumerary teeth; tooth agenesis; crowding	Clinical examination and bite-wing radiographs	Children born with clefts exhibited an increased frequency of enamel hypomineralization, supernumerary teeth, and crowding.
Budai, 2001^‡	Hungarian	Sex; age; ethnicity	Convenience	Not described	Cases and controls ranged from 10–12 years	31	31	No	Supernumerary teeth; tooth agenesis	Clinical examination, radiographs, and dental casts	Congenitally missing teeth were more common and supernumerary teeth less common in children born with cleft palate.
Eerens, 2001^*	Belgium	Age, ethnicity	Convenience	Outside cleft region (excluding the lateral incisor in the upper jaw on the cleft side)	8 years 11 months (cases) and 9 years 10 months (controls)	54	250	Intra: 0.991; Inter: 0.994	Tooth agenesis; asymmetric dental development	Orthopantomogram and records	Individuals born with clefts and their siblings showed a significantly higher occurrence of tooth agenesis and asymmetric dental development than individuals born without clefts.
Letra, 2007	Brazil	Ethnicity	Convenience	Outside cleft region (excluding the central incisors, lateral incisors, and canines in the upper jaw on the cleft side)	17.3 years (cases) and 36.8 years (controls)	500	500	No	Tooth agenesis; microdontia; supernumerary teeth; malposition; impaction; malformation; transposition	Clinical examination, radiographs, and medical records	Individuals born with clefts presented considerably more dental anomalies than did control individuals, suggesting a common genetic contribution to these two defects.
Rawashdeh, 2009	Jordan	Age, ethnicity	Convenience	Distribution according to arch and class of teeth	13.4 years (cases) and 14.6 years (controls)	100	60	No	Morphologic irregularities of the crown (11 traits)	Dental casts	A significant increase was noted in the frequency of crown morphologic abnormalities in individuals born with clefts, more frequently peg-shaped maxillary incisors and missing hypocone.

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.

Table 2

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

	Methodologic Scoring System	Jordan, 1966	Schroeder, 1975	Quezada, 1988	Eerens, 2001	Letra, 2007	Rawashdeh, 2009
Whole population or representative sample selection of the population by calculating sample size	1 point	0	0	0	0	0	0
An appropriate sampling frame or method of subject recruitment	1 point	0	0	0	0	0	0
Matching of the controls concerning age and/or gender and/or ethnicity or at least similar groups for comparison	1 point	1	1	1	1	1	1
Objective, suitable, and standard criteria used for measurement of dental anomalies, such as clinical examination, radiographs, dental records, and dental casts	1 point	1	1	1	1	1	1
Distribution of dental anomalies according to region (inside or outside cleft region) or according to arch segment/class of teeth	3 points	0	0	3	3	3	3
Standardized assessment methods by assessors or interviewers, including interobserver and/or intraobserver reliability	1 point	0	0	0	1	0	0
Data that favored statistical analysis such as chi-square test, relative risk (RR), risk difference (RD), odds ratio (OD), and multivariate regression	1 point	1	1	1	1	1	1
Total of points	Maximum score: 9 points	3	3	6	7	6	7
Final Score		C	C	B	B	B	B

The six eligible studies were selected for the meta-analysis. 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 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 = 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 = 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 = 4.99; 95% CI, 2.58 to 9.64) (Fig. 3) and morphologic irregularities of the crown (OR = 5.69; 95% CI, 3.96 to 8.19) (Fig. 4).

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.

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 = 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) 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, 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 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 congenially 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.

Footnotes

Acknowledgments.

We thank CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior) for financial support.

References

Aizenbud

, Camasuvi

, Peled

, Brin

Congenitally missing teeth in the Israeli cleft population.

Cleft Palate Craniofac J. 2005; 42: 314–317.

Budai

, Kocsis

S.G.

, Kokai

, Sagi

, Mari

[Caries, gingivitis and dental abnormalities in patients with cleft lip and palate].

Fogorv Sz. 2001; 94: 197–199.

Cobourne

M.T.

The complex genetics of cleft lip and palate.

Eur J Orthod. 2004; 26: 7–16.

Cox

T.C.

Taking it to the max: the genetic and developmental mechanisms coordinating midfacial morphogenesis and dysmorphology.

Clin Genet. 2004; 65: 163–176.

Dahllof

, Ussisoo-Joandi

, Ideberg

, Modeer

Caries, gingivitis, and dental abnormalities in preschool children with cleft lip and/or palate.

Cleft Palate J. 1989; 26: 233–237; discussion 237–238.

Dewinter

, Quirynen

, Heidbuchel

, Verdonck

, Willems

, Carels

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: 343–350.

Eerens

, Vlietinck

, Heidbuchel

, Van Olmen

, Derom

, Willems

, Carels

Hypodontia and tooth formation in groups of children with cleft, siblings without cleft, and nonrelated controls.

Cleft Palate Craniofac J. 2001; 38: 374–378.

Graber

L.W.

Congenital absence of teeth: a review with emphasis on inheritance patterns.

J Am Dent Assoc. 1978; 96: 266–275.

Higgins

J.P.T.

, Green

Cochrane Handbook for Systematic Reviews of Interventions. Version 4.2.4. [Updated March 2005.] Chichester, United Kingdom: John Wiley & Sons, 2005.

10.

Johnson

D.B.

Some observations on certain developmental den to-alveolar anomalies and the stigmata of cleft.

Dent Pract Dent Rec. 1967; 17: 435–443.

11.

Jordan

R.E.

, Kraus

B.S.

, Neptune

C.M.

Dental abnormalities associated with cleft lip and/or palate.

Cleft Palate J. 1966; 3: 22–55.

12.

Küchler

E.C.

, Motta

, Vieira

A.R.

, Granjeiro

J.M.

Side of dental anomalies and taurodontism as potential clinical markers for cleft subphenotypes.

Cleft Palate Craniofac J. 2011; 48: 103–108.

13.

Larmour

C.J.

, Mossey

P.A.

, Thind

B.S.

, Forgie

A.H.

, Stirrups

D.R.

Hypodontia—a retrospective review of prevalence and etiology. Part I.

Quintessence Int. 2005; 36: 263–270.

14.

Letra

, Menezes

, Granjeiro

J.M.

, Vieira

A.R.

Defining subphenotypes for oral clefts based on dental development.

J Dent Res. 2007; 86: 986–991.

15.

Loney

P.L.

, Chambers

L.W.

, Bennett

K.J.

, Roberts

J.G.

, Stratford

P.W.

Critical appraisal of the health research literature: prevalence or incidence of a health problem.

Chronic Dis Can. 1998; 19: 170–176.

16.

Menezes

, Vieira

A.R.

Dental anomalies as part of the cleft spectrum.

Cleft Palate Craniofac J. 2008; 45: 414–419.

17.

Murray

J.C.

Gene/environment causes of cleft lip and/or palate.

Clin Genet. 2002; 61: 248–256.

18.

Noordzij

, Tripepi

, Dekker

F.W.

, Zoccali

, Tanck

M.W.

, Jager

K.J.

Sample size calculations: basic principles and common pitfalls.

Nephrol Dial Transplant. 2010; 25: 1388–1393.

19.

Owens

J.R.

, Jones

J.W.

, Harris

Epidemiology of facial clefting.

Arch Dis Child. 1985; 60: 521–524.

20.

Poyry

, Ranta

Anomalies in the deciduous dentition outside the cleft region in children with oral clefts.

Proc Finn Dent Soc. 1985; 81: 91–97.

21.

Quezada

M.G.C.

, Hoeksma

J.B.

, van de Velde

J.P.

, Prahl-Andersen

, Kuijpers-Jagtman

A.M.

Dental anomalies in patients with familial and sporadic cleft lip and palate.

J Biol Buccale. 1988; 16: 185–190.

22.

Ranta

A review of tooth formation in children with cleft lip/palate.

Am J Orthod Dentofacial Orthop. 1986; 90: 11–18.

23.

Rawashdeh

M.A.

, Abu Sirdaneh

E.O.

Crown morphologic abnormalities in the permanent: dentition of patients with cleft lip and palate.

J Craniofac Surg. 2009; 20: 465–470.

24.

Ribeiro

L.L.

, Teixeira Das Neves

, Costa

, Ribeiro Gomide

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: 172–175.

25.

Schroeder

D.C.

, Green

L.J.

Frequency of dental trait anomalies in cleft, sibling, and noncleft groups.

J Dent Res. 1975; 54: 802–807.

26.

Shapira

, Lubit

, Kuftinec

M.M.

Hypodontia in children with various types of clefts.

Angle Orthod. 2000; 70: 16–21.

27.

Slayton

R.L.

, Williams

, Murray

J.C.

, Wheeler

J.J.

, Lidral

A.C.

, Nishimura

C.J.

Genetic association studies of cleft lip and/or palate with hypodontia outside the cleft region.

Cleft Palate Craniofac J. 2003; 40: 274–279.

28.

Stahl

, Grabowski

, Wigger

Epidemiology of Hoffmeister's “genetically determined predisposition to disturbed development of the dentition” in patients with cleft lip and palate.

Cleft Palate Craniofac J. 2006; 43: 457–465.

29.

van den Boogaard

M.J.

, Dorland

, Beemer

F.A.

, van Amstel

H.K.

MSX1 mutation is associated with orofacial clefting and tooth agenesis in humans.

Nat Genet. 2000; 24: 342–343.

30.

Vieira

A.R.

Oral clefts and syndromic forms of tooth agenesis as models for genetics of isolated tooth agenesis.

J Dent Res. 2003; 82: 162–165.

31.

Vieira

A.R.

, McHenry

T.G.

, Daack-Hirsch

, Murray

J.C.

, Marazita

M.L.

A genome wide linkage scan for cleft lip and palate and dental anomalies.

Am J Med Genet A. 2008; 146: 1406–1413.