The Cleft Palate–Craniofacial Journal 52(4) pp. 395–404 July 2015 Ó Copyright 2015 American Cleft Palate-Craniofacial Association
ORIGINAL ARTICLE Presurgical Unilateral Cleft Lip Anthropometrics and the Presence of Dental Anomalies Gregory S. Antonarakis, D.D.S., M.Sc., Ph.D., David M. Fisher, M.D., F.R.C.S.(C.), F.A.C.S. Objective: To investigate associations between cleft lip anthropometrics and dental anomalies in the permanent dentition in unilateral cleft lip patients. Design: Retrospective cross-sectional study. Patients: Children with unilateral clefts of the lip, with or without cleft palate. Methods: Anthropometric lip measurements, made immediately prior to lip repair, were available for each patient. The presence of dental anomalies in the permanent dentition was assessed radiographically. The presence of associations between anthropometric lip measurements and prevalence rates of different dental anomalies were determined using logistic regression analyses. Results: In the 122 included patients, the cleft lateral lip element was deficient in height in 80% and in transverse length in 84% of patients. Patients with more deficient cleft side lateral lip height and less deficient cleft side lateral lip transverse length were more likely to present with cleft side maxillary lateral incisor agenesis. On the other hand, patients with a less deficient cleft side lateral lip height and more deficient cleft side lateral lip transverse length were more likely to present with a cleft side supernumerary maxillary lateral incisor. When looking only at incomplete clefts, the cleft side lateral lip transverse length deficiency was more predictive of the presence of supernumerary maxillary lateral incisors (P ¼ .030), while for complete clefts, the cleft side lateral lip height deficiency was more predictive of the presence of maxillary lateral incisor agenesis (P ¼ .035). Conclusions: In patients with unilateral clefts, cleft lip anthropometrics have a predictive role in determining the occurrence of dental anomalies. KEY WORDS:
cleft lip anthropometrics, dental anomalies
Numerous studies have reported the presence of dental anomalies in association with various forms of oral clefts (Jordan et al., 1966; Ranta, 1986; Tsai et al., 1998; Shapira et al., 2000; Slayton et al., 2003; Letra et al., 2007). Tannure et al. (2012) in a meta-analysis found a significant association between oral clefts and dental anomalies (tooth agenesis, supernumerary teeth, and crown abnormalities). Studies have found that as many as 96.7% of individuals with a cleft have at least one dental anomaly (Akcam et al., 2010). Apart from the fact that individuals with clefts present considerably more dental anomalies than do individuals without clefts, numerous studies have proposed that the frequency and proportion of dental anomalies appear to be directly related to cleft phenotype (Schroeder and Green, 1975; Tsai et al., 1998; van den Boogaard et al., 2000; Eerens et al., 2001; Dewinter et al., 2003; Slayton et al., 2003; Vieira, 2003; Stahl et al., 2006; Letra et al., 2007; da Silva et al., 2008; Akcam et al., 2010; Al-Jamal et al., 2010; Aizenbud et al., 2011). Dental anomalies may represent an additional clinical marker for the definition of more specific cleft subphenotypes, suggesting a common background between the two conditions (Weinberg et al., 2006; Letra et al., 2007; Menezes and Vieira, 2008; Kuchler ¨ et al., 2011).
The occurrence of orofacial clefts and the development of tooth germs have a close relationship in terms of embryological development, timing, and anatomic position (Ranta, 1986; Tsai et al., 1998; Schutte and Murray, 1999; Wei et al., 2000; Stahl et al., 2006), neural crest cell origin (Ewings and Carstens, 2009), and genetic background and pathways during development (van den Boogaard et al., 2000; Slayton et al., 2003; Vieira, 2003; Vieira, 2008; Nakatomi et al., 2010). This implies that the most critical events of tooth, lip, and palate formation occur almost concurrently (Menezes and Vieira, 2008).
Dr. Antonarakis is Craniofacial Orthodontic Fellow, Division of Orthodontics, The Hospital for Sick Children, Toronto, Ontario, Canada. Dr. Fisher is Medical Director, Cleft Lip and Palate Program, Division of Plastic Surgery, The Hospital for Sick Children, Toronto, Ontario, Canada, and Associate Professor, Department of Surgery, University of Toronto, Toronto, Ontario, Canada. Submitted June 2013; Revised September 2013; Accepted October 2013. Address correspondence to: Gregory S. Antonarakis, Division of Orthodontics, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada. E-mail gregory.antonarakis@ sickkids.ca. DOI: 10.1597/13-145 395
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Clefting is part of a complex malformation often associated with dental anomalies resulting from disturbed development of the dentition (Stahl et al., 2006). The most common dental anomaly found in cleft lip and palate patients is tooth agenesis (Akcam et al., 2010). Early reports have claimed that the increased incidence of tooth agenesis in children with clefts might be a result not only of the genetic factors directly affecting tooth agenesis but also of the factors causing the cleft itself, suggesting that the same etiologic factors may be responsible for both the formation of clefts and tooth agenesis in the affected children (Bailit et al., 1968; Ranta et al., 1983). It has been put forward that the high rate of agenesis near the cleft may be due to a deficiency in blood supply or to a deficiency in the ´ , 1994; Vichi mesenchymal mass (Jiroutova´ and Mullerova ¨ and Franchi, 1995; Ribeiro et al., 2003). Absence of the lateral incisor could be the result of tissue insufficiency in the medial nasal and/or maxillary process during embryological development (Hovorakova et al., 2006). The presence of supernumerary teeth is the second most common dental anomaly found in cleft lip and palate patients (Ribeiro et al., 2003). This occurs possibly because of disturbances during the dental development stage of histodifferentiation or morphodifferentiation and may develop as a result of fragmentation of the dental lamina during cleft formation as a distinct structure or from dichotomy of a tooth bud (Vichi and Franchi, 1995). There have been relatively few previous attempts to associate the size/extent of the cleft to dental anomalies. Karsten et al. (2005) found that the more extended the length of the cleft, the higher the number of missing second premolars in isolated cleft palate children. Larson et al. (1998) also found an association between the sagittal extent of the cleft in children with isolated cleft palate and hypodontia where those with large clefts presented more missing second premolars and maxillary lateral incisors. In cleft lip and/or palate patients, lip anthropometric measurements have been shown to have a large variation (Boorer et al., 2011). To the best of the authors’ knowledge, no previous attempt has been made to explore associations between the size/extent of the unilateral cleft lip and dental anomalies. The aim of the current study was thus to investigate associations between cleft lip anthropometrics and dental anomalies in the permanent dentition in unilateral cleft lip patients (with or without cleft palate), specifically looking at alterations in tooth number both inside and outside the cleft area as well as tooth size defects in the cleft area. MATERIALS
AND
METHODS
The current study was approved by the institutional research ethics board. A retrospective chart review was carried out to locate children with unilateral clefts of the lip born between 1999 and 2005, who had their primary lip repair carried out by the senior author (D.M.F.) and for
whom standardized diagnostic records (at least a panoramic radiograph) were available at the age of 6 years or older. Exclusion criteria were the following: children whose cleft was part of a craniofacial syndrome; children with median clefts; children who had radiographs available only after their alveolar bone graft, because of the possibility of the surgeon’s having extracted teeth in the cleft site at the time of the bone graft; children without sufficient diagnostic records allowing the diagnosis of dental anomalies; children whose radiographs were not of diagnostic clarity; children who had radiographs taken only after teeth were extracted due to dental decay or orthodontic treatment or after trauma; and children who had diagnostic records in which there was persistent doubt regarding the presence of dental anomalies. Determination of Cleft Phenotype The determination of cleft phenotype was based on clinical diagnosis. All diagnoses were made from the senior author (D.M.F.) at or soon after birth and confirmed at the time of primary lip repair. Cleft phenotype status was based on laterality (left or right), extent (lip, lip and alveolus, lip and alveolus and palate), and severity (complete or incomplete). Lip Anthropometric Measurements Primary cleft lip repair was carried out between the age of 3 and 6 months (mean age, 4.3 months). All of the anthropometric lip measurements were taken by the senior author (D.M.F.) using calipers, immediately prior to lip repair with the patient under general anesthesia. The vertical height and transverse length measurements of both the cleft and noncleft sides of the lip were recorded to the nearest 0.5 mm. The anthropometric points used for measurements are shown in Figure 1. Medial lip heights were measured from the midline of the labiocolumellar groove (subnasale) to the peaks of Cupid’s bow. The lateral lip height of the noncleft side was measured from the lowest point of the alar base (subalare) to the peak of Cupid’s bow. The lateral lip height of the cleft side was measured from the lowest point of the alar base (subalare) to the proposed peak of Cupid’s bow. The proposed peak of Cupid’s bow was defined according to Noordhoff, as the point along the vermilion-cutaneous junction where the cutaneous roll and red line (vermilion-mucosal junction) begin to converge medially (Noordhoff, 1997). The lateral lip transverse length of the noncleft side was measured from the oral commissure to the peak of Cupid’s bow. The lateral lip transverse length of the cleft side was measured from the oral commissure to the proposed peak of Cupid’s bow at Noordhoff’s point.
Antonarakis and Fisher, CLEFT LIP ANTHROPOMETRICS AND DENTAL ANOMALIES
FIGURE 1 The medial lip heights (A) and (B) were measured from the midline of the labiocolumellar groove (subnasale) to the peaks of Cupid’s bow. The noncleft side lateral lip height (C) was measured from the lowest point of the alar base (subalare) to the peak of Cupid’s bow. The cleft side lateral lip height (D) was measured from the lowest point of the alar base (subalare) to the proposed peak of Cupid’s bow. The noncleft side lateral lip transverse length (E) was measured from the oral commissure to the peak of Cupid’s bow. The cleft side lateral lip transverse length (F) was measured from the oral commissure to the proposed peak of Cupid’s bow. (Reproduced with permission from Boorer et al., 2011.)
Dental Anomalies A chart review of all eligible subjects was conducted to identify the presence of any dental anomalies in the permanent dentition including hypodontia, hyperodontia, or microdontia. Hypodontia (tooth agenesis) was defined as the existence of at least one congenitally missing tooth, other than the third molar. Hyperodontia (supernumerary teeth) was defined as the presence of an additional tooth to the normal series found in any region of the dental arch. Microdontia (primarily pegshaped lateral incisors) was defined as the presence of at least one tooth smaller than what would be considered within the normal range. Findings from the chart review were confirmed by evaluation of available radiographs, intraoral photographs, and plaster models (dental casts). A thorough radiographic examination for dental anomalies of permanent teeth was undertaken using available panoramic, periapical, and occlusal radiographs. Sequential radiographs were used where available to confirm any dental anomalies. Third molars were not included in the assessment. Given that premolar tooth buds may sometimes develop late, agenesis of
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these teeth was confirmed only if the contralateral tooth was already present or if the tooth buds of the second permanent molars, which normally form after premolars, could be visualized. All records were examined by one observer (G.S.A.) to eliminate interexaminer differences. Patterns of tooth agenesis were identified using the tooth agenesis code (TAC) developed by van Wijk and Tan (2006). The TAC uses a binary system in which 0 denotes presence and 1 denotes absence of a tooth, and a specific value is assigned to each missing tooth. This specific value corresponding to a missing tooth is determined by calculating 2(n-1), in which n ¼ the tooth number. The teeth are numbered 1 to 8, where 1 represents a central incisor and 8 a third molar (Peck and Peck, 1996). The sum of these values is calculated for each quadrant, representing a unique value for each tooth agenesis pattern, the TAC. According to this system, a quadrant without tooth agenesis would have a TAC value of 0, and a quadrant with complete tooth agenesis would have a TAC value of 255. Patterns of tooth agenesis of the whole dentition of an individual ´ et al., 2007), are described using the TACoverall (Creton which is composed of the TAC for each quadrant, providing a unique number for the particular tooth agenesis pattern. The TACoverall score is presented in the format TACq1.TACq2.TACq3.TACq4, representing the first to fourth quadrants (q1 to q4) of the dentition, respectively. Analysis All data were analyzed using the Statistical Package for Social Science version 21.0 for Windows (SPSS Inc., Chicago, IL). Descriptive statistics (mean, standard deviation, range) were calculated for the anthropometric lip measurements, and independent sample t tests were used to investigate the presence of statistically significant differences between lip measurements and gender, laterality, or different cleft phenotypes (complete versus incomplete; complete with Simonart bands versus without Simonart bands). Frequencies (prevalence rates) and distributions were calculated for the different types of dental anomalies and tooth agenesis patterns. Chi-square and Fisher exact tests were used to investigate the presence of statistically significant differences between the prevalence of dental anomalies and gender, laterality, or different cleft phenotypes (complete versus incomplete; complete with Simonart band versus without Simonart band). To assess associations between anthropometric lip measurements and prevalence rates of different types of dental anomalies, logistic regression was used where the dependent variable was a discrete variable, denoted by 0 (absence of the particular dental anomaly) or 1 (presence of the
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TABLE 1
Distribution of Cleft Phenotypes
All Patients (n ¼ 122)
Incomplete Cleft Lip (n ¼ 25)
Incomplete Cleft Lip and Alveolus (n ¼ 15)
Complete Cleft Lip and Alveolus (n ¼ 4)
Complete Cleft Lip and Palate With Simonart Band (n ¼ 11)
Complete Cleft Lip and Palate Without Simonart Band (n ¼ 67)
Gender Male Female
81 41
14 11
11 4
3 1
10 1
43 24
Laterality Left Right
78 44
20 5
11 4
2 2
9 2
36 31
particular dental anomaly). Statistical significance was set at the P , .05 level. Intraexaminer reliability was assessed, using kappa statistics, by reevaluating 20 randomly selected radiographs after a 1-week interval. Agreement was calculated for the observations of missing teeth, supernumerary teeth, and tooth size defects in the cleft area. RESULTS Sample A total of 194 children were located with unilateral clefts of the lip born between 1999 and 2005 who had their primary lip repair carried out by the senior author (D.M.F.). Of these, 122 children fit the inclusion and exclusion criteria. In the total sample, 66% were male while 34% were female, and 64% were left-sided clefts while 36% were right-sided clefts. The distribution of cleft phenotypes according to gender and laterality is shown in Table 1. Lip Anthropometric Data Mean height and transverse length measurements, as well as differences between the cleft and noncleft sides, for the total study sample and the different cleft phenotypes are listed in Table 2. The cleft side anthropometric measurements are presented as a percentage of the noncleft anthropometric measurements in Tables 3 and 4. No gender differences were found for the lip measurements. Left-sided clefts showed a more deficient cleft lateral lip height (P ¼ .007) than right-sided clefts. Comparing the different cleft phenotypes, incomplete clefts showed a less deficient cleft lateral lip height (P , .001) but a more deficient cleft lateral lip transverse length (P ¼ .013) than complete clefts without Simonart bands. No significant differences in lip anthropometrics were found when comparing complete clefts with to those without Simonart bands. No significant association was found when relating lip anthropometrics to the age at primary cleft lip repair.
The totality of the patient sample had a cleft medial lip deficiency. Extreme cleft medial lip deficiency (defined as .1 standard deviation from the mean) was seen in 10 patients, half of which were patients with incomplete cleft lip. A total of 98 of 122 patients (80%) had a cleft lateral lip height deficiency, while 103 of 122 patients (84%) had a cleft lateral lip transverse length deficiency. Extreme cleft lateral lip height deficiency was seen in 18 patients, all of which presented with complete unilateral clefts of the lip and palate. Extreme cleft lateral lip transverse length deficiency was observed in 16 patients, more than half of which occurred in patients with an incomplete cleft of the lip. A combined cleft lateral lip element deficiency (both height and transverse length) was found in 79 of 122 patients (65%), but no patient had a combined extreme cleft lateral lip element deficiency. There was an inverse correlation between cleft lateral lip height and cleft lateral lip transverse length (Pearson correlation coefficient ¼ .394, P , .001). Dental Anomalies The prevalences of dental anomalies according to cleft phenotype are presented in Table 5. No significant differences were found when comparing boys to girls or left-sided to right-sided clefts, apart from central incisor agenesis on the cleft side, which was more common in right-sided than in left-sided clefts (P ¼ .045). When comparing the prevalence of dental anomalies in different cleft types, complete clefts had a higher prevalence of dental anomalies in general compared with incomplete clefts, especially with regard to lateral incisor agenesis on the cleft side (P , .001) and maxillary premolar agenesis on the cleft side (P ¼ .005), but incomplete clefts had a higher prevalence of supernumerary lateral incisors on the cleft side (P ¼ .009). When comparing complete clefts without Simonart bands to those with Simonart bands, those with Simonart bands showed a higher prevalence of microdontic lateral incisors on the cleft side (P ¼ .049). When looking solely at dental agenesis (Table 6), complete clefts had a higher prevalence of agenesis of one tooth when compared with incomplete clefts (P ¼ .014), but no significant differences were found with the
Antonarakis and Fisher, CLEFT LIP ANTHROPOMETRICS AND DENTAL ANOMALIES
TABLE 2
399
Summary of Anthropometric Data* Incomplete Cleft Lip (n ¼ 25)
Incomplete Cleft Lip and Alveolus (n ¼ 15)
Complete Cleft Lip and Alveolus (n ¼ 4)
Complete Cleft Lip and Palate With Simonart Band (n ¼ 11)
Complete Cleft Lip and Palate Without Simonart Band (n ¼ 67)
Medial lip height noncleft side Mean (SD) 9.3 (1.4) Range 6.5 to 13
8.9 (1.1) 7 to 11
8.9 (1.1) 7 to 11.5
9.3 (1.3) 8 to 11
8.7 (0.8) 8 to 10
9.6 (1.5) 6.5 to 13
Medial lip height cleft side Mean (SD) 6.9 (1.2) Range 4 to 10.5
6.5 (1.0) 5 to 9
6.4 (1.3) 4 to 9
6.8 (1.2) 6 to 8.5
6.4 (0.6) 5 to 7
7.2 (1.2) 4.5 to 10.5
Medial lip height difference Mean (SD) 2.4 (0.7) Range 1 to 4.5
2.4 (0.9) 1 to 4
2.4 (0.5) 2 to 3
2.5 (0.4) 2 to 3
2.3 (0.6) 1.5 to 3.5
2.4 (0.7) 1 to 4.5
Lateral lip height noncleft side Mean (SD) 10.8 (1.6) Range 7 to 15.5
9.7 (1.3) 15 to 29
10.2 (1.1) 7 to 12
10.9 (1.3) 9 to 12
10.8 (1.2) 8 to 12.5
11.4 (1.6) 7 to 15.5
Lateral lip height cleft side Mean (SD) 8.5 (1.6) Range 5 to 17
9.2 (1.3) 14 to 27
9.0 (1.1) 7 to 11
7.1 (1.4) 6 to 9
8.7 (1.4) 7 to 12
8.1 (1.8) 5 to 17
Lateral lip height difference Mean (SD) 2.4 (2.1) Range 4 to 7
0.5 (1.0) 1 to 3
1.2 (1.6) 2.5 to 3
3.8 (1.6) 2.5 to 6
2.1 (1.7) 2 to 3.5
3.3 (2.0) 4 to 7
Lateral lip transverse length noncleft side Mean (SD) 18.3 (3.2) 21.2 (3.5) Range 13 to 29 7.5 to 12
19.1 (2.3) 16 to 23
17.3 (2.6) 15 to 21
18.5 (2.5) 15 to 24
17.1 (2.5) 13 to 26
Lateral lip transverse length cleft side Mean (SD) 15.9 (2.8) 18.7 (3.8) Range 11 to 27 7 to 11.5
15.4 (2.0) 12.5 to 20
15.5 (2.0) 14 to 18.5
15.3 (1.3) 13 to 17
15.2 (1.9) 11 to 22
Lateral lip transverse length difference Mean (SD) 2.4 (2.0) 2.5 (2.0) Range 2 to 10 0 to 6
3.7 (1.8) 1.5 to 7
1.8 (1.2) 0 to 2.5
3.2 (2.8) 0 to 10
1.9 (1.7) 2 to 7
Measurements
All Patients (n ¼ 122)
* All measurements are in millimeters. Negative values in range indicate cleft side value greater than noncleft side value.
prevalence of two or more missing teeth. No significant differences were observed for tooth agenesis when comparing complete clefts with Simonart bands to those without. Table 7 shows the patterns of tooth agenesis using the TAC. Intraexaminer reliability showed no inconsistencies for the observations of missing teeth or supernumerary teeth (kappa values of 1.00), whereas the kappa value was 0.95 for tooth size defects.
Associations A positive association was found between the medial lip height ratio and lateral incisor agenesis; namely, those with a larger medial lip height ratio were more likely to have agenesis of the maxillary lateral incisor (P ¼ .047; Table 8). However, a negative association was found between the medial lip height ratio and the presence of supernumerary lateral incisors (P ¼ .004).
TABLE 3 Mean Cleft Lip Height and Transverse Length Measurements Expressed as a Percentage of the Noncleft Side Measurements, According to Gender and Laterality Gender
Laterality
All Patients (n ¼ 122)
Male (n ¼ 81)
Female (n ¼ 41)
P Value*
Left (n ¼ 78)
Right (n ¼ 44)
P Value*
Medial lip height Mean (SD) Range
74 (8) 56 to 88
74 (7) 56 to 88
74 (7) 56 to 88
n.s.
74 (7) 56 to 88
75 (7) 56 to 88
n.s.
Lateral lip height Mean (SD) Range
80 (18) 42 to 136
80 (17) 46 to 136
80 (19) 42 to 120
n.s.
74 (17) 42 to 114
83 (17) 50 to 136
.007
Lateral lip transverse length Mean (SD) 88 (9) Range 58 to 114
87 (9) 58 to 114
90 (10) 66 to 100
n.s.
87 (9) 67 to 104
88 (10) 58 to 114
n.s.
Measurements
* Statistical significance is set at P , .05. Nonsignificance is denoted by n.s.
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TABLE 4
Mean Cleft Lip Height and Transverse Length Measurements Expressed as a Percentage of the Noncleft Side Measurements*
Incomplete Cleft Lip (n ¼ 25)
Incomplete Cleft Lip and Alveolus (n ¼ 15)
Complete Cleft Lip and Alveolus (n ¼ 4)
Complete Cleft Lip and Palate With Simonart Band (n ¼ 11)
Complete Cleft Lip and Palate Without Simonart Band (n ¼ 67)
Incomplete Versus Complete P Value†
Simonart Versus Without Simonart P Value†
Medial lip height Mean (SD) Range
73 (9) 56 to 88
72 (7) 57 to 82
73 (4) 67 to 77
74 (6) 63 to 82
75 (6) 61 to 88
n.s.
n.s.
Lateral lip height Mean (SD) Range
95 (10) 73 to 111
90 (18) 70 to 136
66 (12) 50 to 78
81 (16) 70 to 120
72 (16) 42 to 131
,.001
n.s.
Lateral lip transverse length Mean (SD) 88 (9) Range 71 to 100
81 (8) 66 to 91
90 (7) 85 to 100
84 (12) 58 to 100
90 (9) 66 to 114
.013
n.s.
Measurements
* Comparisons between incomplete and complete clefts do not include clefts with Simonart bands. Comparisons between clefts with or without Simonart bands include only complete clefts. † Statistical significance is set at P , .05. Nonsignificance is denoted by n.s.
cleft side maxillary central incisor (P ¼ .011). On the contrary, those with a larger lateral lip height ratio were more likely to present with a supernumerary maxillary lateral incisor tooth (P ¼ .013). Similar to the medial lip height ratio, the lateral lip transverse length ratio showed analogous associations. Those with a larger ratio were more likely to have tooth agenesis (P ¼ .007), particularly of the maxillary lateral
For the lateral lip height ratio, those with a smaller lateral lip height ratio were more likely to have tooth agenesis (P , .001), particularly of the cleft side maxillary lateral incisor (P , .001) and premolar (P ¼ .047), as well as the noncleft side maxillary lateral incisor (P ¼ .045) and premolar (P ¼ .001). Those with a smaller lateral lip height ratio were also more likely to present with microdontia (P ¼ .031), particularly of the TABLE 5
Prevalence of Dental Anomalies According to Cleft Type*
Incomplete Cleft Lip
Dental Anomaly
Incomplete Cleft Lip and Alveolus
Complete Cleft Lip and Alveolus
Complete Cleft Lip and Palate With Simonart Band
Complete Cleft Lip and Palate Without Simonart Band
P Value† Simonart Incomplete Versus Versus Without Complete Simonart
Frequency
%
Frequency
%
Frequency
%
Frequency
%
Frequency
%
Presence of dental anomaly No dental anomaly
12 13
48.0 52.0
12 3
80.0 20.0
3 1
75.0 25.0
10 1
90.9 9.1
61 6
91.0 9.0
,.001 ,.001
n.s. n.s.
Overall Tooth agenesis Lateral incisor agenesis Central incisor agenesis Other tooth agenesis Supernumary lateral incisor Microdontic lateral incisor Microdontic central incisor
3 2 — 1 8 3 —
12.0 8.0 — 4.0 32.0 12.0 —
4 3 — 3 4 6 —
26.7 20.0 — 20.0 26.7 40.0 —
3 3 1 — — 1 —
75.0 75.0 25.0 — — 15.0 —
4 3 — 1 1 7 1
36.3 27.3 — 9.1 9.1 63.6 9.1
42 37 2 16 7 21 6
62.7 55.2 3.0 23.9 10.4 31.3 9.0
,.001 ,.001 n.s. n.s. .009 n.s. n.s.
n.s. n.s. n.s. n.s. n.s. .049 n.s.
Cleft side Lateral incisor agenesis Central incisor agenesis Supernumary lateral incisor Microdontic lateral incisor Microdontic central incisor Maxillary premolar agenesis
2 — 8 2 — 1
8.0 — 32.0 8.0 — 4.0
3 — 4 6 — —
20.0 — 26.7 40.0 — —
2 1 — 1 — —
50.0 25.0 — 25.0 — —
3 — 1 7 1 1
27.3 — 9.1 63.6 9.1 9.1
37 2 7 21 6 16
55.2 3.0 10.4 31.3 9.0 23.9
,.001 n.s. .009 n.s. n.s. .005
n.s. n.s. n.s. .049 n.s. n.s.
Noncleft side Lateral incisor agenesis Supernumary lateral incisor Microdontic lateral incisor Maxillary premolar agenesis
— 1 1 —
— 4.0 4.0 —
— — — —
— — — —
— — — —
— — — —
1 — — —
9.1 — — —
6 — 2 4
9.0 — 3.0 6.0
n.s. n.s. n.s. n.s.
n.s. n.s. n.s. n.s.
Total
25
15
100
4
100
11
100
100
67
100
* Comparisons between incomplete and complete clefts do not include clefts with Simonart bands. Comparisons between clefts with or without Simonart bands include only complete clefts. † Statistical significance is set at P , .05. Nonsignificance is denoted by n.s.
n.s. n.s. n.s. n.s. n.s. n.s. * Comparisons between incomplete and complete clefts do not include clefts with Simonart bands. Comparisons between clefts with or without Simonart bands include only complete clefts. † Statistical significance is set at P , .05. Nonsignificance is denoted by n.s.
37.3 32.8 17.9 7.5 3.0 1.5 100 25 22 12 5 2 1 67 0 1 2 3 4 8 Total
66 33 15 5 2 1 122
54.1 27.0 12.3 4.1 1.6 0.8 100
22 3 — — — — 25
88.0 12.0 — — — — 100
11 2 2 — — — 15
73.3 13.3 13.3 — — — 100
1 3 — — — — 4
25.0 75.0 — — — — 100
7 3 1 — — — 11
63.6 27.3 28.6 — — — 100
% Frequency % Frequency Frequency % Frequency Frequency
All Patients
%
Frequency
%
Imcomplete Cleft Lip and Alveolus Incomplete Cleft Lip
,.001 .014 n.s. n.s. n.s. n.s.
Simonart Versus Without Simonart Number of Missing Teeth
TABLE 6
Prevalence of Dental Agenesis (Total Number of Teeth Absent)*
Complete Cleft Lip and Alveolus
%
Complete Cleft Lip and Palate With Simonart Band
Complete Cleft Lip and Palate Without Simonart Band
Incomplete Versus Complete
P Value†
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401
incisor (P ¼ .007). Those with a smaller ratio were more likely to present with a supernumerary maxillary lateral incisor tooth (P ¼ .023). When looking at incomplete or complete cleft types individually, the following statistically significant associations were found. For incomplete clefts, those with a smaller lateral lip transverse length ratio were more likely to exhibit a cleft side supernumerary maxillary lateral incisor tooth (Nagelkerke R2 ¼ .158; P ¼ .030). For complete clefts, those with a smaller lateral lip height ratio were more likely to demonstrate tooth agenesis (Nagelkerke R2 ¼ .080; P ¼ .037), particularly cleft side maxillary lateral incisor agenesis (Nagelkerke R2 ¼ .083; P ¼ .035). No other associations were observed. DISCUSSION The results of the present study suggest that in patients with unilateral clefts of the lip (with or without cleft palate), cleft lip anthropometrics have a predictive role in determining the occurrence of dental anomalies such as alterations in tooth number (tooth agenesis or the presence of supernumerary teeth) as well as tooth size defects (microdontia) in the cleft area. Patients with a less deficient cleft side medial lip height, more deficient cleft side lateral lip height, and less deficient cleft side lateral lip transverse length are more likely to present with cleft side maxillary lateral incisor agenesis. A deficient cleft side lateral lip height is also associated with a higher presence of microdontia on the cleft side. On the other hand, patients with a more deficient cleft side medial lip height, less deficient cleft side lateral lip height, and more deficient cleft side lateral lip transverse length are more likely to present with a cleft side supernumerary maxillary lateral incisor. Cleft phenotype may be one of the factors, apart from cleft lip anthropometrics per se, that determines the presence of dental anomalies, with tooth agenesis being more common in complete clefts while supernumerary teeth are more common in incomplete clefts. When looking at incomplete or complete cleft types individually, however, associations are still observed. For incomplete clefts, cleft side lateral lip transverse length deficiency seems to be more predictive of the presence of supernumerary maxillary lateral incisors. For complete clefts, cleft side lateral lip height deficiency is more predictive of the presence of maxillary lateral incisor agenesis. Variability in cleft lip anthropometric measurements exists not only between different cleft types but also within different cleft types. Our results suggest that within the spectrum of the deformity for each cleft type, the degree of cleft lateral lip element hypoplasia is predictive of the occurrence of dental anomalies and perhaps even predictive of global lateral segment hypoplasia. Cleft lip and palate presents a complex phenotypic variation and reflects a breakdown in the normal mecha-
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TABLE 7
TAC
Tooth Agenesis Code (TAC), Number of Missing Teeth and Corresponding Missing Teeth, Frequency, and Percentage of TAC
Number
0.0.0.0 0.2.0.0 2.0.0.0 0.18.0.0 18.0.0.0 2.2.0.0 0.0.0.2 1.0.0.0 0.16.0.0 16.0.0.0 3.0.0.0 0.2.0.16 0.2.16.0 0.24.0.0 2.3.0.0 19.0.0.0 18.16.0.0 0.18.16.0 16.0.16.16 18.18.0.0 20.16.0.0 24.24.24.24
0 1 1 2 2 2 1 1 1 1 2 2 2 2 3 3 3 3 3 4 4 8
Total
—
Tooth/Teeth Missing
All Patients
Incomplete Cleft Lip
Incomplete Cleft Lip and Alveolus
Complete Cleft Lip and Alveolus
Complete Cleft Lip and Palate With Simonart Band
Complete Cleft Lip and Palate Without Simonart Band
Frequency
%
Frequency
%
Frequency
%
Frequency
%
Frequency
%
Frequency
%
66 19 10 5 3 3 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1
54.1 15.6 8.2 4.1 2.5 2.5 0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.8
22 2 — — — — — — — 1 — — — — — — — — — — — —
88.0 8.0 — — — — — — — 4.0 — — — — — — — — — — — —
11 — 1 — — — 1 — — — — 1 1 — — — — — — — — —
73.3 — 6.7 — — — 6.7 — — — — 6.7 6.7 — — — — — — — — —
1 1 1 — — — — 1 — — — — — — — — — — — — — —
25.0 25.0 25.0 — — — — 25.0 — — — — — — — — — — — — — —
7 2 — — — 1 — — 1 — — — — — — — — — — — — —
63.6 28.6 — — — 14.3 — — 14.3 — — — — — — — — — — — — —
25 14 8 5 3 2 — — — — 1 — — 1 1 1 1 1 1 1 1 1
37.3 20.1 11.9 7.5 4.5 3.0 — — — — 1.5 — — 1.5 1.5 1.5 1.5 1.5 1.5 1.5 1.5 1.5
None 22 12 22, 25 12, 25 12, 22 42 11 25 15 11, 12 12, 45 12, 35 24, 25 12, 21, 22 11, 12, 15 12, 15, 25 22, 25, 35 15, 35, 45 12, 15, 22, 25 13, 15, 22, 25 14, 15, 24, 25, 34, 35, 44, 45 Total
122
100
25
100
nisms involved during early embryologic development of the face (Cobourne, 2004). It cannot be assumed that all types of cleft have the same influence on tooth development, since the alveolar process can be affected to a greater or lesser extent (da Silva et al,. 2008). During embryogenesis, lack of coalescence between the maxillary and medial nasal prominences probably causes a deficiency in mesenchymal mass, which may lead to clefting. The odontogenic potential of the lateral incisor is probably related to these ´ , 1994; Tsai et al., 1998; regions (Jiroutova´ and Mullerova ¨ Ribeiro et al., 2003), and this assumption may explain hypodontia of the maxillary lateral incisor and also the presence of supernumerary teeth. Dental anomaly manifestations may be a natural consequence of local development factors that cause the oral cleft (de Lima Pedro et al., 2012). These anomalies originate during odontogenesis, especially during the initiation and proliferation stages of the tooth bud during intrauterine life, and lateral incisors TABLE 8
15
100
4
100
11
100
67
100
erupt in critical terminal areas of the dental lamina and are located in the embryologic fusion areas (Thesleff, 1996). Thus, while cleft patients with a severe deficiency of mesenchymal mass may present hypodontia of the lateral incisor, those with mild deficiency may present with a lateral incisor mesial or distal to the cleft or even a supernumerary tooth, depending on the location of the odontogenic mass in the maxillary or medial nasal processes. Children with complete clefts may be more likely to develop hypodontia rather than hyperodontia or microdontia because of the degree of mesenchymal tissue deficiency and consequently local defects (Aizenbud et al., 2011). The prevalence of missing tooth buds, however, has been said to increase with the severity of the cleft, with the highest prevalences found in complete clefts of the lip, alveolus, and palate (Stahl et al., 2006; Wu et al., 2011). On the other hand, in children with incomplete clefts, the
Associations Between Anthropometric Lip Measurements and Different Types of Dental Anomalies Medial Lip Height Ratio
Dental Anomaly General tooth agenesis Cleft side lateral incisor agenesis Cleft side maxillary premolar agenesis Noncleft side lateral incisor agenesis Noncleft side maxillary premolar agenesis Supernumerary lateral incisor Microdontia Microdontic cleft side central incisor * Statistical significance is set at P , .05.
Lateral Lip Height Ratio
Lateral Lip Transverse Length Ratio
Nagelkerke R2
P Value*
Nagelkerke R2
P Value*
Nagelkerke R2
P Value*
— .043 — — — .106 — —
— .047 — — — .004 — —
.155 .158 .056 .104 .339 .083 .051 .144
,.001 ,.001 .047 .045 .001 .013 .031 .011
.077 .077 — — — .070 — —
.007 .007 — — — .023 — —
Antonarakis and Fisher, CLEFT LIP ANTHROPOMETRICS AND DENTAL ANOMALIES
mesenchymal tissue deficiency is smaller, resulting in a higher prevalence of crown malformations such as microdontia or hyperodontia reflected in sufficient tissue space for dichotomic tooth bud development (da Silva et al., 2008; Wu et al., 2011). It has been proposed that the presence of supernumerary lateral incisors is greatest in cases of cleft lip only and decreases as the extent of the cleft increases (Nagai et al., 1965; Ranta, 1986; Stahl et al., 2006). Paranaiba et al. (2013), based on their population, suggested that the extension of the cleft did not correlate with the frequency of dental anomalies. They go on to say that the correlation between cleft extension and dental anomalies is controversial and thus warrants further research (Paranaiba et al., 2013). The results of the present study suggest that perhaps apart from the cleft phenotype, the severity of the cleft as judged by cleft lip anthropometrics may be important in determining dental anomaly patterns. The deficiency of the lateral lip element, in the vertical and/or transverse dimension, may be correlated with the spectrum of dental anomalies, from agenesis of teeth to the presence of supernumerary teeth. The extent of cleft side lateral lip element deficiency has not attracted much attention in either the clinical or the research setting. The focus is often turned toward the severity of the cleft as determined by the extent of primary or/and secondary palate involvement and maxillary arch dimensions. The present study highlights the variation seen in cleft lateral lip element deficiency, both in the vertical and in the transverse dimensions and the potential correlations that this deficiency may have with dental anomalies. One could speculate that cleft lateral lip element deficiency may correlate with other hard tissue variables such as maxillary arch transverse and anteroposterior dimensions and ultimately with maxillary growth. Research in this direction is required to evaluate such possible correlations. CONCLUSIONS In patients with unilateral cleft lip with or without cleft palate, there is a wide variability in the degree of deficiency of the cleft lateral lip element, both in the vertical and in the transverse dimension. We have demonstrated that the extent of this deficiency predicts the presence of dental anomalies. In patients with incomplete clefts, cleft side lateral lip transverse length deficiency is correlated with the presence of supernumerary maxillary lateral incisors. In patients with complete clefts, cleft side lateral lip height deficiency is correlated with the presence of maxillary lateral incisor agenesis. REFERENCES Aizenbud D, Coval M, Hazan-Molina H, Harari D. Isolated soft tissue cleft lip: epidemiology and associated dental anomalies. Oral Dis. 2011;17:221–231.
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Akcam MO, Evirgen S, Uslu O, Memikoglu ˘ UT. Dental anomalies in individuals with cleft lip and/or palate. Eur J Orthod. 2010;32:207– 213. Al-Jamal GA, Hazza’a AM, Rawashdeh MA. Prevalence of dental anomalies in a population of cleft lip and palate patients. Cleft Palate Craniofac J. 2010;47:413–420. Bailit HL, Doykos JD, Swanson LT. Dental development in children with cleft palate. J Dent Res. 1968;47:664. Boorer CJ, Cho DC, Vijayasekaran VS, Fisher DM. Presurgical unilateral cleft lip anthropometrics: implications for the choice of repair technique. Plast Reconstr Surg. 2011;127:774–780. Cobourne MT. The complex genetics of cleft lip and palate. Eur J Orthod. 2004;26:7–16. ´ Creton MA, Cune MS, Verhoeven W, Meijer GJ. Patterns of missing teeth in a population of oligodontia patients. Int J Prosthodont. 2007;20:409–413. da Silva AP, Costa B, de Carvalho Carrara CF. Dental anomalies of number in the permanent dentition of patients with bilateral cleft lip: radiographic study. Cleft Palate Craniofac J. 2008;45:473–476. de Lima Pedro R, Faria MD, de Castro Costa M, Vieira AR. Dental anomalies in children born with clefts: a case-control study. Cleft Palate Craniofac J. 2012;49:e64–e68. 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;40:343–350. Eerens K, Vlietinck R, Heidbuchel K, et al. Hypodontia and tooth ¨ formation in groups of children with cleft, siblings without cleft, and nonrelated controls. Cleft Palate Craniofac J. 2001;38:374–378. Ewings EL, Carstens MH. Neuroembryology and functional anatomy of craniofacial clefts. Indian J Plast Surg. 2009;42:S19–S34. Hovorakova M, Lesot H, Peterkova R, Peterka M. Origin of the deciduous upper lateral incisor and its clinical aspects. J Dent Res. 2006;85:167–171. ´ Z. The occurrence of hypodontia in patients Jiroutova´ O, Mullerova ¨ with cleft lip and/or palate. Acta Chir Plast. 1994;36:53–56. Jordan RE, Krauss BS, Neptune CM. Dental abnormalities associated with cleft lip and/or palate. Cleft Palate J. 1966;3:22–55. Karsten A, Larson M, Larson O. Length of the cleft in relation to the incidence of hypodontia of the second premolar and to inheritance of cleft lip and palate in children with isolated cleft palate. Scand J Plast Reconstr Surg Hand Surg. 2005;39:283–286. Kuchler EC, da Motta LG, Vieira AR, Granjeiro JM. Side of dental ¨ anomalies and taurodontism as potential clinical markers for cleft subphenotypes. Cleft Palate Craniofac J. 2011;48:103–108. Larson M, Hellquist R, Jakobsson OP. Dental abnormalities and ectopic eruption in patients with isolated cleft palate. Scand J Plast Reconstr Surg Hand Surg. 1998;32:203–212. Letra A, Menezes R, Granjeiro JM, Vieira AR. Defining subphenotypes for oral clefts based on dental development. J Dent Res. 2007;86:986–991. Menezes R, Vieira AR. Dental anomalies as part of the cleft spectrum. Cleft Palate Craniofac J. 2008;45:414–419. Nagai I, Fujiki Y, Fuchihata H, Yoshimoto T. Supernumerary tooth associated with cleft lip and palate. J Am Dent Assoc. 1965;70:642– 647. Nakatomi M, Wang XP, Key D, et al. Genetic interactions between Pax9 and Msx1 regulate lip development and several stages of tooth morphogenesis. Dev Biol. 2010;340:438–449. Noordhoff MS. The Surgical Technique for the Unilateral Cleft LipNasal Deformity. Taipei, Taiwan: Noordhoff Craniofacial Foundation; 1997. Paranaiba LM, Coletta RD, Swerts MS, Quintino RP, de Barros LM, Martelli-Junior H. Prevalence of dental anomalies in patients with nonsyndromic cleft lip and/or palate in a Brazilian population. Cleft Palate Craniofac J. 2013;50:400–405.
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Peck S, Peck L. Tooth numbering progress. Angle Orthod. 1996;66:83– 84. Ranta R. A review of tooth formation in children with cleft lip/palate. Am J Orthod Dentofacial Orthop. 1986;90:11–18. Ranta R, Stegars T, Rintala AE. Correlations of hypodontia in children with isolated cleft palate. Cleft Palate J. 1983;20:163–165. Ribeiro LL, Neves LT, Costa B, Gomide MR. 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. Schroeder DC, Green LJ. Frequency of dental trait anomalies in cleft, sibling, and noncleft groups. J Dent Res. 1975;54:802–807. Schutte BC, Murray JC. The many faces and factors of orofacial clefts. Hum Mol Genet. 1999;8:1853–1859. Shapira Y, Lubit E, Kuftinec MM. Hypodontia in children with various typed of clefts. Angle Orthod. 2000;70:16–21. 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;40:274–279. Stahl F, Grabowski R, Wigger K. 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. Tannure PN, Oliveira CA, Maia LC, Vieira AR, Granjeiro JM, de Castro Costa M. Prevalence of dental anomalies in nonsyndromic individuals with cleft lip and palate: a systematic review and metaanalysis. Cleft Palate Craniofac J. 2012;49:194–200.
Thesleff I. Two genes for missing teeth. Nat Genet. 1996;13:379–380. Tsai TP, Haung CS, Haung CC, See LC. Distribution patterns of primary and permanent dentition in children with unilateral complete cleft lip and palate. Cleft Palate Craniofac J. 1998;35:154–160. 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;24:342–343. van Wijk AJ, Tan SP. A numeric code for identifying patterns of human tooth agenesis: a new approach. Eur J Oral Sci. 2006;114:97–101. Vichi M, Franchi L. Abnormalities of the maxillary incisors in children with cleft lip and palate. ASDC J Dent Child. 1995;62:412–417. Vieira AR. Oral clefts and syndromic forms of tooth agenesis as models for genetics of isolated tooth agenesis. J Dent Res. 2003;82:162–165. Vieira AR. Unraveling human cleft lip and palate research. J Dent Res. 2008;87:119–125. Wei X, Senders C, Owiti GO, et al. The origin and development of the upper lateral incisor and premaxilla in normal and cleft lip/palate monkeys induced with cyclophosphamide. Cleft Palate Craniofac J. 2000;37:571–583. Weinberg SM, Neiswanger K, Martin RA, et al. The Pittsburgh OralFacial Cleft study: expanding the cleft phenotype. Background and justification. Cleft Palate Craniofac J. 2006;43:7–20. Wu TT, Chen PK, Lo LJ, Cheng MC, Ko EW. The characteristics and distribution of dental anomalies in patients with cleft. Chang Gung Med J. 2011;34:306–314.
ORIGINAL ARTICLE Presurgical Unilateral Cleft Lip Anthropometrics and the Presence of Dental Anomalies Gregory S. Antonarakis, D.D.S., M.Sc., Ph.D., David M. Fisher, M.D., F.R.C.S.(C.), F.A.C.S. Objective: To investigate associations between cleft lip anthropometrics and dental anomalies in the permanent dentition in unilateral cleft lip patients. Design: Retrospective cross-sectional study. Patients: Children with unilateral clefts of the lip, with or without cleft palate. Methods: Anthropometric lip measurements, made immediately prior to lip repair, were available for each patient. The presence of dental anomalies in the permanent dentition was assessed radiographically. The presence of associations between anthropometric lip measurements and prevalence rates of different dental anomalies were determined using logistic regression analyses. Results: In the 122 included patients, the cleft lateral lip element was deficient in height in 80% and in transverse length in 84% of patients. Patients with more deficient cleft side lateral lip height and less deficient cleft side lateral lip transverse length were more likely to present with cleft side maxillary lateral incisor agenesis. On the other hand, patients with a less deficient cleft side lateral lip height and more deficient cleft side lateral lip transverse length were more likely to present with a cleft side supernumerary maxillary lateral incisor. When looking only at incomplete clefts, the cleft side lateral lip transverse length deficiency was more predictive of the presence of supernumerary maxillary lateral incisors (P ¼ .030), while for complete clefts, the cleft side lateral lip height deficiency was more predictive of the presence of maxillary lateral incisor agenesis (P ¼ .035). Conclusions: In patients with unilateral clefts, cleft lip anthropometrics have a predictive role in determining the occurrence of dental anomalies. KEY WORDS:
cleft lip anthropometrics, dental anomalies
Numerous studies have reported the presence of dental anomalies in association with various forms of oral clefts (Jordan et al., 1966; Ranta, 1986; Tsai et al., 1998; Shapira et al., 2000; Slayton et al., 2003; Letra et al., 2007). Tannure et al. (2012) in a meta-analysis found a significant association between oral clefts and dental anomalies (tooth agenesis, supernumerary teeth, and crown abnormalities). Studies have found that as many as 96.7% of individuals with a cleft have at least one dental anomaly (Akcam et al., 2010). Apart from the fact that individuals with clefts present considerably more dental anomalies than do individuals without clefts, numerous studies have proposed that the frequency and proportion of dental anomalies appear to be directly related to cleft phenotype (Schroeder and Green, 1975; Tsai et al., 1998; van den Boogaard et al., 2000; Eerens et al., 2001; Dewinter et al., 2003; Slayton et al., 2003; Vieira, 2003; Stahl et al., 2006; Letra et al., 2007; da Silva et al., 2008; Akcam et al., 2010; Al-Jamal et al., 2010; Aizenbud et al., 2011). Dental anomalies may represent an additional clinical marker for the definition of more specific cleft subphenotypes, suggesting a common background between the two conditions (Weinberg et al., 2006; Letra et al., 2007; Menezes and Vieira, 2008; Kuchler ¨ et al., 2011).
The occurrence of orofacial clefts and the development of tooth germs have a close relationship in terms of embryological development, timing, and anatomic position (Ranta, 1986; Tsai et al., 1998; Schutte and Murray, 1999; Wei et al., 2000; Stahl et al., 2006), neural crest cell origin (Ewings and Carstens, 2009), and genetic background and pathways during development (van den Boogaard et al., 2000; Slayton et al., 2003; Vieira, 2003; Vieira, 2008; Nakatomi et al., 2010). This implies that the most critical events of tooth, lip, and palate formation occur almost concurrently (Menezes and Vieira, 2008).
Dr. Antonarakis is Craniofacial Orthodontic Fellow, Division of Orthodontics, The Hospital for Sick Children, Toronto, Ontario, Canada. Dr. Fisher is Medical Director, Cleft Lip and Palate Program, Division of Plastic Surgery, The Hospital for Sick Children, Toronto, Ontario, Canada, and Associate Professor, Department of Surgery, University of Toronto, Toronto, Ontario, Canada. Submitted June 2013; Revised September 2013; Accepted October 2013. Address correspondence to: Gregory S. Antonarakis, Division of Orthodontics, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada. E-mail gregory.antonarakis@ sickkids.ca. DOI: 10.1597/13-145 395
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Clefting is part of a complex malformation often associated with dental anomalies resulting from disturbed development of the dentition (Stahl et al., 2006). The most common dental anomaly found in cleft lip and palate patients is tooth agenesis (Akcam et al., 2010). Early reports have claimed that the increased incidence of tooth agenesis in children with clefts might be a result not only of the genetic factors directly affecting tooth agenesis but also of the factors causing the cleft itself, suggesting that the same etiologic factors may be responsible for both the formation of clefts and tooth agenesis in the affected children (Bailit et al., 1968; Ranta et al., 1983). It has been put forward that the high rate of agenesis near the cleft may be due to a deficiency in blood supply or to a deficiency in the ´ , 1994; Vichi mesenchymal mass (Jiroutova´ and Mullerova ¨ and Franchi, 1995; Ribeiro et al., 2003). Absence of the lateral incisor could be the result of tissue insufficiency in the medial nasal and/or maxillary process during embryological development (Hovorakova et al., 2006). The presence of supernumerary teeth is the second most common dental anomaly found in cleft lip and palate patients (Ribeiro et al., 2003). This occurs possibly because of disturbances during the dental development stage of histodifferentiation or morphodifferentiation and may develop as a result of fragmentation of the dental lamina during cleft formation as a distinct structure or from dichotomy of a tooth bud (Vichi and Franchi, 1995). There have been relatively few previous attempts to associate the size/extent of the cleft to dental anomalies. Karsten et al. (2005) found that the more extended the length of the cleft, the higher the number of missing second premolars in isolated cleft palate children. Larson et al. (1998) also found an association between the sagittal extent of the cleft in children with isolated cleft palate and hypodontia where those with large clefts presented more missing second premolars and maxillary lateral incisors. In cleft lip and/or palate patients, lip anthropometric measurements have been shown to have a large variation (Boorer et al., 2011). To the best of the authors’ knowledge, no previous attempt has been made to explore associations between the size/extent of the unilateral cleft lip and dental anomalies. The aim of the current study was thus to investigate associations between cleft lip anthropometrics and dental anomalies in the permanent dentition in unilateral cleft lip patients (with or without cleft palate), specifically looking at alterations in tooth number both inside and outside the cleft area as well as tooth size defects in the cleft area. MATERIALS
AND
METHODS
The current study was approved by the institutional research ethics board. A retrospective chart review was carried out to locate children with unilateral clefts of the lip born between 1999 and 2005, who had their primary lip repair carried out by the senior author (D.M.F.) and for
whom standardized diagnostic records (at least a panoramic radiograph) were available at the age of 6 years or older. Exclusion criteria were the following: children whose cleft was part of a craniofacial syndrome; children with median clefts; children who had radiographs available only after their alveolar bone graft, because of the possibility of the surgeon’s having extracted teeth in the cleft site at the time of the bone graft; children without sufficient diagnostic records allowing the diagnosis of dental anomalies; children whose radiographs were not of diagnostic clarity; children who had radiographs taken only after teeth were extracted due to dental decay or orthodontic treatment or after trauma; and children who had diagnostic records in which there was persistent doubt regarding the presence of dental anomalies. Determination of Cleft Phenotype The determination of cleft phenotype was based on clinical diagnosis. All diagnoses were made from the senior author (D.M.F.) at or soon after birth and confirmed at the time of primary lip repair. Cleft phenotype status was based on laterality (left or right), extent (lip, lip and alveolus, lip and alveolus and palate), and severity (complete or incomplete). Lip Anthropometric Measurements Primary cleft lip repair was carried out between the age of 3 and 6 months (mean age, 4.3 months). All of the anthropometric lip measurements were taken by the senior author (D.M.F.) using calipers, immediately prior to lip repair with the patient under general anesthesia. The vertical height and transverse length measurements of both the cleft and noncleft sides of the lip were recorded to the nearest 0.5 mm. The anthropometric points used for measurements are shown in Figure 1. Medial lip heights were measured from the midline of the labiocolumellar groove (subnasale) to the peaks of Cupid’s bow. The lateral lip height of the noncleft side was measured from the lowest point of the alar base (subalare) to the peak of Cupid’s bow. The lateral lip height of the cleft side was measured from the lowest point of the alar base (subalare) to the proposed peak of Cupid’s bow. The proposed peak of Cupid’s bow was defined according to Noordhoff, as the point along the vermilion-cutaneous junction where the cutaneous roll and red line (vermilion-mucosal junction) begin to converge medially (Noordhoff, 1997). The lateral lip transverse length of the noncleft side was measured from the oral commissure to the peak of Cupid’s bow. The lateral lip transverse length of the cleft side was measured from the oral commissure to the proposed peak of Cupid’s bow at Noordhoff’s point.
Antonarakis and Fisher, CLEFT LIP ANTHROPOMETRICS AND DENTAL ANOMALIES
FIGURE 1 The medial lip heights (A) and (B) were measured from the midline of the labiocolumellar groove (subnasale) to the peaks of Cupid’s bow. The noncleft side lateral lip height (C) was measured from the lowest point of the alar base (subalare) to the peak of Cupid’s bow. The cleft side lateral lip height (D) was measured from the lowest point of the alar base (subalare) to the proposed peak of Cupid’s bow. The noncleft side lateral lip transverse length (E) was measured from the oral commissure to the peak of Cupid’s bow. The cleft side lateral lip transverse length (F) was measured from the oral commissure to the proposed peak of Cupid’s bow. (Reproduced with permission from Boorer et al., 2011.)
Dental Anomalies A chart review of all eligible subjects was conducted to identify the presence of any dental anomalies in the permanent dentition including hypodontia, hyperodontia, or microdontia. Hypodontia (tooth agenesis) was defined as the existence of at least one congenitally missing tooth, other than the third molar. Hyperodontia (supernumerary teeth) was defined as the presence of an additional tooth to the normal series found in any region of the dental arch. Microdontia (primarily pegshaped lateral incisors) was defined as the presence of at least one tooth smaller than what would be considered within the normal range. Findings from the chart review were confirmed by evaluation of available radiographs, intraoral photographs, and plaster models (dental casts). A thorough radiographic examination for dental anomalies of permanent teeth was undertaken using available panoramic, periapical, and occlusal radiographs. Sequential radiographs were used where available to confirm any dental anomalies. Third molars were not included in the assessment. Given that premolar tooth buds may sometimes develop late, agenesis of
397
these teeth was confirmed only if the contralateral tooth was already present or if the tooth buds of the second permanent molars, which normally form after premolars, could be visualized. All records were examined by one observer (G.S.A.) to eliminate interexaminer differences. Patterns of tooth agenesis were identified using the tooth agenesis code (TAC) developed by van Wijk and Tan (2006). The TAC uses a binary system in which 0 denotes presence and 1 denotes absence of a tooth, and a specific value is assigned to each missing tooth. This specific value corresponding to a missing tooth is determined by calculating 2(n-1), in which n ¼ the tooth number. The teeth are numbered 1 to 8, where 1 represents a central incisor and 8 a third molar (Peck and Peck, 1996). The sum of these values is calculated for each quadrant, representing a unique value for each tooth agenesis pattern, the TAC. According to this system, a quadrant without tooth agenesis would have a TAC value of 0, and a quadrant with complete tooth agenesis would have a TAC value of 255. Patterns of tooth agenesis of the whole dentition of an individual ´ et al., 2007), are described using the TACoverall (Creton which is composed of the TAC for each quadrant, providing a unique number for the particular tooth agenesis pattern. The TACoverall score is presented in the format TACq1.TACq2.TACq3.TACq4, representing the first to fourth quadrants (q1 to q4) of the dentition, respectively. Analysis All data were analyzed using the Statistical Package for Social Science version 21.0 for Windows (SPSS Inc., Chicago, IL). Descriptive statistics (mean, standard deviation, range) were calculated for the anthropometric lip measurements, and independent sample t tests were used to investigate the presence of statistically significant differences between lip measurements and gender, laterality, or different cleft phenotypes (complete versus incomplete; complete with Simonart bands versus without Simonart bands). Frequencies (prevalence rates) and distributions were calculated for the different types of dental anomalies and tooth agenesis patterns. Chi-square and Fisher exact tests were used to investigate the presence of statistically significant differences between the prevalence of dental anomalies and gender, laterality, or different cleft phenotypes (complete versus incomplete; complete with Simonart band versus without Simonart band). To assess associations between anthropometric lip measurements and prevalence rates of different types of dental anomalies, logistic regression was used where the dependent variable was a discrete variable, denoted by 0 (absence of the particular dental anomaly) or 1 (presence of the
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TABLE 1
Distribution of Cleft Phenotypes
All Patients (n ¼ 122)
Incomplete Cleft Lip (n ¼ 25)
Incomplete Cleft Lip and Alveolus (n ¼ 15)
Complete Cleft Lip and Alveolus (n ¼ 4)
Complete Cleft Lip and Palate With Simonart Band (n ¼ 11)
Complete Cleft Lip and Palate Without Simonart Band (n ¼ 67)
Gender Male Female
81 41
14 11
11 4
3 1
10 1
43 24
Laterality Left Right
78 44
20 5
11 4
2 2
9 2
36 31
particular dental anomaly). Statistical significance was set at the P , .05 level. Intraexaminer reliability was assessed, using kappa statistics, by reevaluating 20 randomly selected radiographs after a 1-week interval. Agreement was calculated for the observations of missing teeth, supernumerary teeth, and tooth size defects in the cleft area. RESULTS Sample A total of 194 children were located with unilateral clefts of the lip born between 1999 and 2005 who had their primary lip repair carried out by the senior author (D.M.F.). Of these, 122 children fit the inclusion and exclusion criteria. In the total sample, 66% were male while 34% were female, and 64% were left-sided clefts while 36% were right-sided clefts. The distribution of cleft phenotypes according to gender and laterality is shown in Table 1. Lip Anthropometric Data Mean height and transverse length measurements, as well as differences between the cleft and noncleft sides, for the total study sample and the different cleft phenotypes are listed in Table 2. The cleft side anthropometric measurements are presented as a percentage of the noncleft anthropometric measurements in Tables 3 and 4. No gender differences were found for the lip measurements. Left-sided clefts showed a more deficient cleft lateral lip height (P ¼ .007) than right-sided clefts. Comparing the different cleft phenotypes, incomplete clefts showed a less deficient cleft lateral lip height (P , .001) but a more deficient cleft lateral lip transverse length (P ¼ .013) than complete clefts without Simonart bands. No significant differences in lip anthropometrics were found when comparing complete clefts with to those without Simonart bands. No significant association was found when relating lip anthropometrics to the age at primary cleft lip repair.
The totality of the patient sample had a cleft medial lip deficiency. Extreme cleft medial lip deficiency (defined as .1 standard deviation from the mean) was seen in 10 patients, half of which were patients with incomplete cleft lip. A total of 98 of 122 patients (80%) had a cleft lateral lip height deficiency, while 103 of 122 patients (84%) had a cleft lateral lip transverse length deficiency. Extreme cleft lateral lip height deficiency was seen in 18 patients, all of which presented with complete unilateral clefts of the lip and palate. Extreme cleft lateral lip transverse length deficiency was observed in 16 patients, more than half of which occurred in patients with an incomplete cleft of the lip. A combined cleft lateral lip element deficiency (both height and transverse length) was found in 79 of 122 patients (65%), but no patient had a combined extreme cleft lateral lip element deficiency. There was an inverse correlation between cleft lateral lip height and cleft lateral lip transverse length (Pearson correlation coefficient ¼ .394, P , .001). Dental Anomalies The prevalences of dental anomalies according to cleft phenotype are presented in Table 5. No significant differences were found when comparing boys to girls or left-sided to right-sided clefts, apart from central incisor agenesis on the cleft side, which was more common in right-sided than in left-sided clefts (P ¼ .045). When comparing the prevalence of dental anomalies in different cleft types, complete clefts had a higher prevalence of dental anomalies in general compared with incomplete clefts, especially with regard to lateral incisor agenesis on the cleft side (P , .001) and maxillary premolar agenesis on the cleft side (P ¼ .005), but incomplete clefts had a higher prevalence of supernumerary lateral incisors on the cleft side (P ¼ .009). When comparing complete clefts without Simonart bands to those with Simonart bands, those with Simonart bands showed a higher prevalence of microdontic lateral incisors on the cleft side (P ¼ .049). When looking solely at dental agenesis (Table 6), complete clefts had a higher prevalence of agenesis of one tooth when compared with incomplete clefts (P ¼ .014), but no significant differences were found with the
Antonarakis and Fisher, CLEFT LIP ANTHROPOMETRICS AND DENTAL ANOMALIES
TABLE 2
399
Summary of Anthropometric Data* Incomplete Cleft Lip (n ¼ 25)
Incomplete Cleft Lip and Alveolus (n ¼ 15)
Complete Cleft Lip and Alveolus (n ¼ 4)
Complete Cleft Lip and Palate With Simonart Band (n ¼ 11)
Complete Cleft Lip and Palate Without Simonart Band (n ¼ 67)
Medial lip height noncleft side Mean (SD) 9.3 (1.4) Range 6.5 to 13
8.9 (1.1) 7 to 11
8.9 (1.1) 7 to 11.5
9.3 (1.3) 8 to 11
8.7 (0.8) 8 to 10
9.6 (1.5) 6.5 to 13
Medial lip height cleft side Mean (SD) 6.9 (1.2) Range 4 to 10.5
6.5 (1.0) 5 to 9
6.4 (1.3) 4 to 9
6.8 (1.2) 6 to 8.5
6.4 (0.6) 5 to 7
7.2 (1.2) 4.5 to 10.5
Medial lip height difference Mean (SD) 2.4 (0.7) Range 1 to 4.5
2.4 (0.9) 1 to 4
2.4 (0.5) 2 to 3
2.5 (0.4) 2 to 3
2.3 (0.6) 1.5 to 3.5
2.4 (0.7) 1 to 4.5
Lateral lip height noncleft side Mean (SD) 10.8 (1.6) Range 7 to 15.5
9.7 (1.3) 15 to 29
10.2 (1.1) 7 to 12
10.9 (1.3) 9 to 12
10.8 (1.2) 8 to 12.5
11.4 (1.6) 7 to 15.5
Lateral lip height cleft side Mean (SD) 8.5 (1.6) Range 5 to 17
9.2 (1.3) 14 to 27
9.0 (1.1) 7 to 11
7.1 (1.4) 6 to 9
8.7 (1.4) 7 to 12
8.1 (1.8) 5 to 17
Lateral lip height difference Mean (SD) 2.4 (2.1) Range 4 to 7
0.5 (1.0) 1 to 3
1.2 (1.6) 2.5 to 3
3.8 (1.6) 2.5 to 6
2.1 (1.7) 2 to 3.5
3.3 (2.0) 4 to 7
Lateral lip transverse length noncleft side Mean (SD) 18.3 (3.2) 21.2 (3.5) Range 13 to 29 7.5 to 12
19.1 (2.3) 16 to 23
17.3 (2.6) 15 to 21
18.5 (2.5) 15 to 24
17.1 (2.5) 13 to 26
Lateral lip transverse length cleft side Mean (SD) 15.9 (2.8) 18.7 (3.8) Range 11 to 27 7 to 11.5
15.4 (2.0) 12.5 to 20
15.5 (2.0) 14 to 18.5
15.3 (1.3) 13 to 17
15.2 (1.9) 11 to 22
Lateral lip transverse length difference Mean (SD) 2.4 (2.0) 2.5 (2.0) Range 2 to 10 0 to 6
3.7 (1.8) 1.5 to 7
1.8 (1.2) 0 to 2.5
3.2 (2.8) 0 to 10
1.9 (1.7) 2 to 7
Measurements
All Patients (n ¼ 122)
* All measurements are in millimeters. Negative values in range indicate cleft side value greater than noncleft side value.
prevalence of two or more missing teeth. No significant differences were observed for tooth agenesis when comparing complete clefts with Simonart bands to those without. Table 7 shows the patterns of tooth agenesis using the TAC. Intraexaminer reliability showed no inconsistencies for the observations of missing teeth or supernumerary teeth (kappa values of 1.00), whereas the kappa value was 0.95 for tooth size defects.
Associations A positive association was found between the medial lip height ratio and lateral incisor agenesis; namely, those with a larger medial lip height ratio were more likely to have agenesis of the maxillary lateral incisor (P ¼ .047; Table 8). However, a negative association was found between the medial lip height ratio and the presence of supernumerary lateral incisors (P ¼ .004).
TABLE 3 Mean Cleft Lip Height and Transverse Length Measurements Expressed as a Percentage of the Noncleft Side Measurements, According to Gender and Laterality Gender
Laterality
All Patients (n ¼ 122)
Male (n ¼ 81)
Female (n ¼ 41)
P Value*
Left (n ¼ 78)
Right (n ¼ 44)
P Value*
Medial lip height Mean (SD) Range
74 (8) 56 to 88
74 (7) 56 to 88
74 (7) 56 to 88
n.s.
74 (7) 56 to 88
75 (7) 56 to 88
n.s.
Lateral lip height Mean (SD) Range
80 (18) 42 to 136
80 (17) 46 to 136
80 (19) 42 to 120
n.s.
74 (17) 42 to 114
83 (17) 50 to 136
.007
Lateral lip transverse length Mean (SD) 88 (9) Range 58 to 114
87 (9) 58 to 114
90 (10) 66 to 100
n.s.
87 (9) 67 to 104
88 (10) 58 to 114
n.s.
Measurements
* Statistical significance is set at P , .05. Nonsignificance is denoted by n.s.
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Cleft Palate–Craniofacial Journal, July 2015, Vol. 52 No. 4
TABLE 4
Mean Cleft Lip Height and Transverse Length Measurements Expressed as a Percentage of the Noncleft Side Measurements*
Incomplete Cleft Lip (n ¼ 25)
Incomplete Cleft Lip and Alveolus (n ¼ 15)
Complete Cleft Lip and Alveolus (n ¼ 4)
Complete Cleft Lip and Palate With Simonart Band (n ¼ 11)
Complete Cleft Lip and Palate Without Simonart Band (n ¼ 67)
Incomplete Versus Complete P Value†
Simonart Versus Without Simonart P Value†
Medial lip height Mean (SD) Range
73 (9) 56 to 88
72 (7) 57 to 82
73 (4) 67 to 77
74 (6) 63 to 82
75 (6) 61 to 88
n.s.
n.s.
Lateral lip height Mean (SD) Range
95 (10) 73 to 111
90 (18) 70 to 136
66 (12) 50 to 78
81 (16) 70 to 120
72 (16) 42 to 131
,.001
n.s.
Lateral lip transverse length Mean (SD) 88 (9) Range 71 to 100
81 (8) 66 to 91
90 (7) 85 to 100
84 (12) 58 to 100
90 (9) 66 to 114
.013
n.s.
Measurements
* Comparisons between incomplete and complete clefts do not include clefts with Simonart bands. Comparisons between clefts with or without Simonart bands include only complete clefts. † Statistical significance is set at P , .05. Nonsignificance is denoted by n.s.
cleft side maxillary central incisor (P ¼ .011). On the contrary, those with a larger lateral lip height ratio were more likely to present with a supernumerary maxillary lateral incisor tooth (P ¼ .013). Similar to the medial lip height ratio, the lateral lip transverse length ratio showed analogous associations. Those with a larger ratio were more likely to have tooth agenesis (P ¼ .007), particularly of the maxillary lateral
For the lateral lip height ratio, those with a smaller lateral lip height ratio were more likely to have tooth agenesis (P , .001), particularly of the cleft side maxillary lateral incisor (P , .001) and premolar (P ¼ .047), as well as the noncleft side maxillary lateral incisor (P ¼ .045) and premolar (P ¼ .001). Those with a smaller lateral lip height ratio were also more likely to present with microdontia (P ¼ .031), particularly of the TABLE 5
Prevalence of Dental Anomalies According to Cleft Type*
Incomplete Cleft Lip
Dental Anomaly
Incomplete Cleft Lip and Alveolus
Complete Cleft Lip and Alveolus
Complete Cleft Lip and Palate With Simonart Band
Complete Cleft Lip and Palate Without Simonart Band
P Value† Simonart Incomplete Versus Versus Without Complete Simonart
Frequency
%
Frequency
%
Frequency
%
Frequency
%
Frequency
%
Presence of dental anomaly No dental anomaly
12 13
48.0 52.0
12 3
80.0 20.0
3 1
75.0 25.0
10 1
90.9 9.1
61 6
91.0 9.0
,.001 ,.001
n.s. n.s.
Overall Tooth agenesis Lateral incisor agenesis Central incisor agenesis Other tooth agenesis Supernumary lateral incisor Microdontic lateral incisor Microdontic central incisor
3 2 — 1 8 3 —
12.0 8.0 — 4.0 32.0 12.0 —
4 3 — 3 4 6 —
26.7 20.0 — 20.0 26.7 40.0 —
3 3 1 — — 1 —
75.0 75.0 25.0 — — 15.0 —
4 3 — 1 1 7 1
36.3 27.3 — 9.1 9.1 63.6 9.1
42 37 2 16 7 21 6
62.7 55.2 3.0 23.9 10.4 31.3 9.0
,.001 ,.001 n.s. n.s. .009 n.s. n.s.
n.s. n.s. n.s. n.s. n.s. .049 n.s.
Cleft side Lateral incisor agenesis Central incisor agenesis Supernumary lateral incisor Microdontic lateral incisor Microdontic central incisor Maxillary premolar agenesis
2 — 8 2 — 1
8.0 — 32.0 8.0 — 4.0
3 — 4 6 — —
20.0 — 26.7 40.0 — —
2 1 — 1 — —
50.0 25.0 — 25.0 — —
3 — 1 7 1 1
27.3 — 9.1 63.6 9.1 9.1
37 2 7 21 6 16
55.2 3.0 10.4 31.3 9.0 23.9
,.001 n.s. .009 n.s. n.s. .005
n.s. n.s. n.s. .049 n.s. n.s.
Noncleft side Lateral incisor agenesis Supernumary lateral incisor Microdontic lateral incisor Maxillary premolar agenesis
— 1 1 —
— 4.0 4.0 —
— — — —
— — — —
— — — —
— — — —
1 — — —
9.1 — — —
6 — 2 4
9.0 — 3.0 6.0
n.s. n.s. n.s. n.s.
n.s. n.s. n.s. n.s.
Total
25
15
100
4
100
11
100
100
67
100
* Comparisons between incomplete and complete clefts do not include clefts with Simonart bands. Comparisons between clefts with or without Simonart bands include only complete clefts. † Statistical significance is set at P , .05. Nonsignificance is denoted by n.s.
n.s. n.s. n.s. n.s. n.s. n.s. * Comparisons between incomplete and complete clefts do not include clefts with Simonart bands. Comparisons between clefts with or without Simonart bands include only complete clefts. † Statistical significance is set at P , .05. Nonsignificance is denoted by n.s.
37.3 32.8 17.9 7.5 3.0 1.5 100 25 22 12 5 2 1 67 0 1 2 3 4 8 Total
66 33 15 5 2 1 122
54.1 27.0 12.3 4.1 1.6 0.8 100
22 3 — — — — 25
88.0 12.0 — — — — 100
11 2 2 — — — 15
73.3 13.3 13.3 — — — 100
1 3 — — — — 4
25.0 75.0 — — — — 100
7 3 1 — — — 11
63.6 27.3 28.6 — — — 100
% Frequency % Frequency Frequency % Frequency Frequency
All Patients
%
Frequency
%
Imcomplete Cleft Lip and Alveolus Incomplete Cleft Lip
,.001 .014 n.s. n.s. n.s. n.s.
Simonart Versus Without Simonart Number of Missing Teeth
TABLE 6
Prevalence of Dental Agenesis (Total Number of Teeth Absent)*
Complete Cleft Lip and Alveolus
%
Complete Cleft Lip and Palate With Simonart Band
Complete Cleft Lip and Palate Without Simonart Band
Incomplete Versus Complete
P Value†
Antonarakis and Fisher, CLEFT LIP ANTHROPOMETRICS AND DENTAL ANOMALIES
401
incisor (P ¼ .007). Those with a smaller ratio were more likely to present with a supernumerary maxillary lateral incisor tooth (P ¼ .023). When looking at incomplete or complete cleft types individually, the following statistically significant associations were found. For incomplete clefts, those with a smaller lateral lip transverse length ratio were more likely to exhibit a cleft side supernumerary maxillary lateral incisor tooth (Nagelkerke R2 ¼ .158; P ¼ .030). For complete clefts, those with a smaller lateral lip height ratio were more likely to demonstrate tooth agenesis (Nagelkerke R2 ¼ .080; P ¼ .037), particularly cleft side maxillary lateral incisor agenesis (Nagelkerke R2 ¼ .083; P ¼ .035). No other associations were observed. DISCUSSION The results of the present study suggest that in patients with unilateral clefts of the lip (with or without cleft palate), cleft lip anthropometrics have a predictive role in determining the occurrence of dental anomalies such as alterations in tooth number (tooth agenesis or the presence of supernumerary teeth) as well as tooth size defects (microdontia) in the cleft area. Patients with a less deficient cleft side medial lip height, more deficient cleft side lateral lip height, and less deficient cleft side lateral lip transverse length are more likely to present with cleft side maxillary lateral incisor agenesis. A deficient cleft side lateral lip height is also associated with a higher presence of microdontia on the cleft side. On the other hand, patients with a more deficient cleft side medial lip height, less deficient cleft side lateral lip height, and more deficient cleft side lateral lip transverse length are more likely to present with a cleft side supernumerary maxillary lateral incisor. Cleft phenotype may be one of the factors, apart from cleft lip anthropometrics per se, that determines the presence of dental anomalies, with tooth agenesis being more common in complete clefts while supernumerary teeth are more common in incomplete clefts. When looking at incomplete or complete cleft types individually, however, associations are still observed. For incomplete clefts, cleft side lateral lip transverse length deficiency seems to be more predictive of the presence of supernumerary maxillary lateral incisors. For complete clefts, cleft side lateral lip height deficiency is more predictive of the presence of maxillary lateral incisor agenesis. Variability in cleft lip anthropometric measurements exists not only between different cleft types but also within different cleft types. Our results suggest that within the spectrum of the deformity for each cleft type, the degree of cleft lateral lip element hypoplasia is predictive of the occurrence of dental anomalies and perhaps even predictive of global lateral segment hypoplasia. Cleft lip and palate presents a complex phenotypic variation and reflects a breakdown in the normal mecha-
402
Cleft Palate–Craniofacial Journal, July 2015, Vol. 52 No. 4
TABLE 7
TAC
Tooth Agenesis Code (TAC), Number of Missing Teeth and Corresponding Missing Teeth, Frequency, and Percentage of TAC
Number
0.0.0.0 0.2.0.0 2.0.0.0 0.18.0.0 18.0.0.0 2.2.0.0 0.0.0.2 1.0.0.0 0.16.0.0 16.0.0.0 3.0.0.0 0.2.0.16 0.2.16.0 0.24.0.0 2.3.0.0 19.0.0.0 18.16.0.0 0.18.16.0 16.0.16.16 18.18.0.0 20.16.0.0 24.24.24.24
0 1 1 2 2 2 1 1 1 1 2 2 2 2 3 3 3 3 3 4 4 8
Total
—
Tooth/Teeth Missing
All Patients
Incomplete Cleft Lip
Incomplete Cleft Lip and Alveolus
Complete Cleft Lip and Alveolus
Complete Cleft Lip and Palate With Simonart Band
Complete Cleft Lip and Palate Without Simonart Band
Frequency
%
Frequency
%
Frequency
%
Frequency
%
Frequency
%
Frequency
%
66 19 10 5 3 3 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1
54.1 15.6 8.2 4.1 2.5 2.5 0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.8
22 2 — — — — — — — 1 — — — — — — — — — — — —
88.0 8.0 — — — — — — — 4.0 — — — — — — — — — — — —
11 — 1 — — — 1 — — — — 1 1 — — — — — — — — —
73.3 — 6.7 — — — 6.7 — — — — 6.7 6.7 — — — — — — — — —
1 1 1 — — — — 1 — — — — — — — — — — — — — —
25.0 25.0 25.0 — — — — 25.0 — — — — — — — — — — — — — —
7 2 — — — 1 — — 1 — — — — — — — — — — — — —
63.6 28.6 — — — 14.3 — — 14.3 — — — — — — — — — — — — —
25 14 8 5 3 2 — — — — 1 — — 1 1 1 1 1 1 1 1 1
37.3 20.1 11.9 7.5 4.5 3.0 — — — — 1.5 — — 1.5 1.5 1.5 1.5 1.5 1.5 1.5 1.5 1.5
None 22 12 22, 25 12, 25 12, 22 42 11 25 15 11, 12 12, 45 12, 35 24, 25 12, 21, 22 11, 12, 15 12, 15, 25 22, 25, 35 15, 35, 45 12, 15, 22, 25 13, 15, 22, 25 14, 15, 24, 25, 34, 35, 44, 45 Total
122
100
25
100
nisms involved during early embryologic development of the face (Cobourne, 2004). It cannot be assumed that all types of cleft have the same influence on tooth development, since the alveolar process can be affected to a greater or lesser extent (da Silva et al,. 2008). During embryogenesis, lack of coalescence between the maxillary and medial nasal prominences probably causes a deficiency in mesenchymal mass, which may lead to clefting. The odontogenic potential of the lateral incisor is probably related to these ´ , 1994; Tsai et al., 1998; regions (Jiroutova´ and Mullerova ¨ Ribeiro et al., 2003), and this assumption may explain hypodontia of the maxillary lateral incisor and also the presence of supernumerary teeth. Dental anomaly manifestations may be a natural consequence of local development factors that cause the oral cleft (de Lima Pedro et al., 2012). These anomalies originate during odontogenesis, especially during the initiation and proliferation stages of the tooth bud during intrauterine life, and lateral incisors TABLE 8
15
100
4
100
11
100
67
100
erupt in critical terminal areas of the dental lamina and are located in the embryologic fusion areas (Thesleff, 1996). Thus, while cleft patients with a severe deficiency of mesenchymal mass may present hypodontia of the lateral incisor, those with mild deficiency may present with a lateral incisor mesial or distal to the cleft or even a supernumerary tooth, depending on the location of the odontogenic mass in the maxillary or medial nasal processes. Children with complete clefts may be more likely to develop hypodontia rather than hyperodontia or microdontia because of the degree of mesenchymal tissue deficiency and consequently local defects (Aizenbud et al., 2011). The prevalence of missing tooth buds, however, has been said to increase with the severity of the cleft, with the highest prevalences found in complete clefts of the lip, alveolus, and palate (Stahl et al., 2006; Wu et al., 2011). On the other hand, in children with incomplete clefts, the
Associations Between Anthropometric Lip Measurements and Different Types of Dental Anomalies Medial Lip Height Ratio
Dental Anomaly General tooth agenesis Cleft side lateral incisor agenesis Cleft side maxillary premolar agenesis Noncleft side lateral incisor agenesis Noncleft side maxillary premolar agenesis Supernumerary lateral incisor Microdontia Microdontic cleft side central incisor * Statistical significance is set at P , .05.
Lateral Lip Height Ratio
Lateral Lip Transverse Length Ratio
Nagelkerke R2
P Value*
Nagelkerke R2
P Value*
Nagelkerke R2
P Value*
— .043 — — — .106 — —
— .047 — — — .004 — —
.155 .158 .056 .104 .339 .083 .051 .144
,.001 ,.001 .047 .045 .001 .013 .031 .011
.077 .077 — — — .070 — —
.007 .007 — — — .023 — —
Antonarakis and Fisher, CLEFT LIP ANTHROPOMETRICS AND DENTAL ANOMALIES
mesenchymal tissue deficiency is smaller, resulting in a higher prevalence of crown malformations such as microdontia or hyperodontia reflected in sufficient tissue space for dichotomic tooth bud development (da Silva et al., 2008; Wu et al., 2011). It has been proposed that the presence of supernumerary lateral incisors is greatest in cases of cleft lip only and decreases as the extent of the cleft increases (Nagai et al., 1965; Ranta, 1986; Stahl et al., 2006). Paranaiba et al. (2013), based on their population, suggested that the extension of the cleft did not correlate with the frequency of dental anomalies. They go on to say that the correlation between cleft extension and dental anomalies is controversial and thus warrants further research (Paranaiba et al., 2013). The results of the present study suggest that perhaps apart from the cleft phenotype, the severity of the cleft as judged by cleft lip anthropometrics may be important in determining dental anomaly patterns. The deficiency of the lateral lip element, in the vertical and/or transverse dimension, may be correlated with the spectrum of dental anomalies, from agenesis of teeth to the presence of supernumerary teeth. The extent of cleft side lateral lip element deficiency has not attracted much attention in either the clinical or the research setting. The focus is often turned toward the severity of the cleft as determined by the extent of primary or/and secondary palate involvement and maxillary arch dimensions. The present study highlights the variation seen in cleft lateral lip element deficiency, both in the vertical and in the transverse dimensions and the potential correlations that this deficiency may have with dental anomalies. One could speculate that cleft lateral lip element deficiency may correlate with other hard tissue variables such as maxillary arch transverse and anteroposterior dimensions and ultimately with maxillary growth. Research in this direction is required to evaluate such possible correlations. CONCLUSIONS In patients with unilateral cleft lip with or without cleft palate, there is a wide variability in the degree of deficiency of the cleft lateral lip element, both in the vertical and in the transverse dimension. We have demonstrated that the extent of this deficiency predicts the presence of dental anomalies. In patients with incomplete clefts, cleft side lateral lip transverse length deficiency is correlated with the presence of supernumerary maxillary lateral incisors. In patients with complete clefts, cleft side lateral lip height deficiency is correlated with the presence of maxillary lateral incisor agenesis. REFERENCES Aizenbud D, Coval M, Hazan-Molina H, Harari D. Isolated soft tissue cleft lip: epidemiology and associated dental anomalies. Oral Dis. 2011;17:221–231.
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