Establishing the diagnostic criteria for eruption disorders based on genetic and clinical data.

INTRODUCTION: Proper diagnosis and management of eruption disturbances remains challenging but is critical to a functional occlusion. The objective of this study was to establish definitive criteria to differentiate and diagnose eruption disorders, specifically primary failure of eruption (PFE) and ankylosis. METHODS: Sixty-four affected persons were placed into 3 cohorts: PFE diagnosed through confirmed PTH1R mutation (n = 11), PFE diagnosed based on clinical criteria (n = 47), and ankylosis diagnosed based on clinical criteria (n = 6). These groups were assessed to identify clinical features that differentiate PFE and ankylosis. RESULTS: Ninety-three percent of the subjects in the genetic and clinical PFE cohorts combined (n = 58) and 100% in the genetic PFE cohort had at least 1 infraoccluded first permanent molar. Additionally, a novel functional PTH1R mutation, 1092delG, was identified and linked to PFE in the deciduous dentition. CONCLUSIONS: An infraoccluded, supracrestal first molar is a hallmark of PFE, often involving both arches in the permanent or deciduous dentition, and with unilateral or bilateral affection, infraoccluded second premolar or second molar, and multiple affected adjacent teeth. Our results further suggest that PFE and ankylosis might be clinically indistinguishable without knowledge of prior trauma, treatment history, genetic information, or obliteration of the periodontal ligament space.

Triplets with bilateral palatally displaced canines in association with third molar agenesis: an example of biologically related dental anomaly patterns?

This case series shows male triplets with similarly positioned palatally displaced canines and agenesis of third molars. It supports findings reported previously in the literature suggesting a genetic origin for the palatally displaced canine and other dental anomalies which may be biologically related.

[Tooth and bone research using genetically modified mice].

Teeth and bone are both hard tissues and composed of hydroxyapatite. Tooth development initiates with the invasination of oral epithelium, followed by aggregation of supporting ectomesenchymal cells. From mouse study, numbers of molecules have been discovered to relate tooth development. These discoveries have helped to clarify the responsible genes of human genetic disorders with abnormal tooth number and structure. During tooth development, teeth erupt into the outer environment, oral cavity. From this point, teeth are completely different from bone which is always covered by soft tissues. Tooth eruption is composed of two different processes, that is, eruption pathway formation and vertical tooth movement. In this review, mutant mice with abnormal tooth development and eruption are introduced, and molecular mechanism required for this process is discussed.

Agenesis of maxillary lateral incisors and associated dental anomalies.

INTRODUCTION: The objectives of this study were to evaluate the prevalence of dental anomalies in patients with agenesis of maxillary lateral incisors and to compare the findings with the prevalence of these anomalies in the general population. METHODS: A sample of 126 patients, aged 7 to 35 years, with agenesis of at least 1 maxillary lateral incisor was selected. Panoramic and periapical radiographs and dental casts were used to analyze other associated dental anomalies, including agenesis of other permanent teeth, ectopia of unerupted permanent teeth, microdontia of maxillary lateral incisors, and supernumerary teeth. The occurrence of these anomalies was compared with prevalence data previously reported for the general population. Statistical testing was performed with the chi-square test (P <0.05) and the odds ratio. RESULTS: Patients with maxillary lateral incisor agenesis had a significantly increased prevalence rate of permanent tooth agenesis (18.2%), excluding the third molars. The occurrence of third-molar agenesis in a subgroup aged 14 years or older (n = 76) was 35.5%. The frequencies of maxillary second premolar agenesis (10.3%), mandibular second premolar agenesis (7.9%), microdontia of maxillary lateral incisors (38.8%), and distoangulation of mandibular second premolars (3.9%) were significantly increased in our sample compared with the general population. In a subgroup of patients aged 10 years or older (n = 115), the prevalence of palatally displaced canines was elevated (5.2%). The prevalences of mesioangulation of mandibular second molars and supernumerary teeth were not higher in the sample. CONCLUSIONS: Permanent tooth agenesis, maxillary lateral incisor microdontia, palatally displaced canines, and distoangulation of mandibular second premolars are frequently associated with maxillary lateral incisor agenesis, providing additional evidence of a genetic interrelationship in the causes of these dental anomalies.

Malposition of unerupted mandibular second premolar in children with palatally displaced canines.

OBJECTIVE: To test the hypotheses that (1) the distal angulation of unerupted mandibular premolar (MnP2) is significantly greater in children with palatally displaced canines (PDC) than in those in a control sample; and (2) delayed tooth formation is significantly more frequent in children with both malposed MnP2 and PDC than in children with PDC only. MATERIALS AND METHODS: We examined retrospectively panoramic radiographs from 43 patients with PDC who had no previous orthodontics. A control sample consisted of age- and sex-matched patients. The distal angle formed between the long axis of MnP2 and the tangent to the inferior border was measured. Dental age was evaluated using the Koch classification. RESULTS: A significant difference was observed between the mean inclination of the right side MnP2 in the PDC group (75.4 degrees) and that of the control group (85.8 degrees). This difference was highly statistically significant (P < .0001). The same evaluation was carried out for the left side, with similar results. The average dental age was found to be delayed in patients who showed both abnormalities (malposed MnP2 and PDC) compared with patients who showed the PDC anomaly only. CONCLUSION: Both hypotheses are retained. Statistically, PDC and MnP2 malposition are significantly associated suggesting a common genetic etiology, despite taking place on opposite jaws. While the presence of PDC or MnP2 anomaly has been associated with a delay in tooth formation, we find the presence of both anomalies to show a more profound delay. Our findings suggest a delay in tooth formation as a possible common genetic mechanism for these 2 malposition anomalies.

Ectopic maxillary canines: segregation analysis and a twin study.

The etiology of ectopic canines is controversial, with opinion divided as to a genetic or environmental mechanism. This study addressed the hypothesis that genetic factors play a role in the etiology of ectopic maxillary canines. Sixty-three probands were identified, and information on the dental status of 395 relatives was determined. Pedigrees were constructed and the Relative Risk calculated. Complex segregation analysis was carried out by means of the Pedigree Analysis Package. The best mathematical model obtained was a single dominant gene with autosomal transmission, incomplete penetrance, and highly variable expression. Only two of seven pairs of monozygotic twins were concordant for ectopic canines. This is consistent with environmental or epigenetic variables affecting the phenotype. The low concordance rate is consistent with the low penetrance determined by the segregation analysis and further supports the existence of environmental factors.

Apparently new syndrome of sensorineural hearing loss, retinal pigment epithelium lesions, and discolored teeth.

We report on a family with early-onset sensorineural hearing loss, abnormal retinal pigment epithelium granularity, accumulation of creamy-white lesions at the level of the retinal pigment epithelium particularly superior to the arcade, and selective discoloration (brown) of molars or canine deciduous teeth that follows an apparent autosomal recessive inheritance pattern. This appears to be a new syndrome that can be distinguished from the known otodental, oculo-acoustic and flecked retina syndromes by the occurrence of distinct dental and ocular abnormalities.

Possible relationship between ulnar-mammary syndrome and split hand with aplasia of the ulna syndrome.

We describe a 3-generation family in which mother, maternal grandfather, and 2 (male and female) children have variably manifestations of the ulnar-mammary syndrome, including ulnar ray defects, obesity, hypogenitalism, delayed puberty, hypoplasia of nipples and apocrine glands, and a previously undescribed ectopia of upper canines. The index patient also had split-hand appearance on the right due to complete absence of the 4th ray. To our knowledge this is the first documented example of split hand in the ulnar-mammary syndrome. The hand anomaly raises the question of a possible causal relationship between ulnar-mammary syndrome and the split hand with aplasia of the ulna syndrome, as already hypothesized by Lenz [1980].

Palatal displacement of canine is genetic and related to congenital absence of teeth.

The palatally displaced canine is a harmful complication of dental development. It appears in 1 to 2% of the Western population. According to our clinical experience, this anomaly is seen in families in which missing and peg-shaped teeth are common. It could be caused by the same genetic component that causes incisor-premolar hypodontia. We examined 106 patients who had been operated on and treated orthodontically for palatally impacted canine(s). The patients and their family members were examined for dental anomalies. One hundred and ten first- and 93 second-degree relatives were clinically and radiologically examined, and 35 pedigrees were constructed. Thirty-six percent of the patients had congenitally missing permanent teeth (hypodontia), which is 4.5 times the population prevalence. Hypodontia was noted in 19 to 20% of both the first- and second-degree relatives. This is 2.5 times the population prevalence. Frequency of missing teeth, analyzed by tooth groups, was of the same order as that shown for incisor-premolar hypodontia in the Western population. In six of the 35 pedigrees, a palatally impacted canine was noted in several generations of the same family. Prevalence of this anomaly was 4.9% in the studied group, which is 2.5 times the population prevalence. From the findings, we conclude that the palatally displaced canine belongs to the spectrum of dental abnormalities related to hypodontia.

The palatally displaced canine as a dental anomaly of genetic origin.

Palatal displacement of the maxillary canine tooth is a positional variation thought generally to develop as a result of local factors, such as retained deciduous canines, anomalous permanent lateral incisors, or dental crowding. This article contributes biologic evidence pointing to genetic factors as the primary origin of most palatal displacements and subsequent impactions of maxillary canine teeth. Data gathered from multiple sources are integrated to support a genetic etiology for the palatally displaced canine (PDC) on the basis of five evidential categories: 1. Occurrence of other dental anomalies concomitant with PDC; 2. Bilateral occurrence of PDC; 3. Sex differences in PDC occurrence; 4. Familial occurrence of PDC; 5. Population differences in PDC occurrence. From analysis of available evidence, the PDC positional anomaly appears to be a product of polygenic, multifactorial inheritance.

Palatally displaced canine anomaly in monozygotic twins.

The palatally displaced canine (PDC) anomaly is a tooth malposition occurring in 1% to 3% of most populations. From the results of family studies, the PDC phenotype appears to be under strong genetic influence. In this study we report monozygotic (MZ) twin girls with bilateral PDC expression. The finding of PDC anomaly in MZ twins--to our knowledge, the first such published case--lends further support to evidence of genetic control of the PDC anomaly.

In defense of the guidance theory of palatal canine displacement.

From the foregoing debate it will be quite clear that Peck et al. have provided ample evidence that may be used to fuel the arguments of both sides: 1. Their material does not contradict the possibility that environmental factors may give rise to palatal displacement of canines generated by genetic anomaly of the adjacent teeth. 2. The buccally displaced canine finds itself similarly environmentally compromised by the different factor of crowding which leads to its characteristic buccally ectopic guidance pattern. 3. (a) Canines that are transposed with the premolar, (b) others that have erupted ectopically, high in the buccal sulcus and in the absence of crowding, and (c) certain palatal canines whose root apex is located markedly distant from their designated site, may all be labeled as genetically controlled with a fair degree of confidence. 4. In between these clearly defined entities there exists a "gray area" in which it is probable that the etiology of the individual displaced teeth may be linked to a combination of circumstances that obey premise number 1 and premise number 2, to varying degrees. The guidance theory cannot provide the complete answer to the etiology of the palatally displaced canine. Were this so, we would find PDC every time there was an anomalous or missing lateral incisor. Equally, it may not yet be discounted out of hand and certainly not on the basis of the evidence provided in the article in question.

A controlled study of associated dental anomalies.

The purpose of this study was to reveal patterns of association among seven types of dental anomalies (aplasia of second premolars, small size of maxillary lateral incisors, infraocclusion of primary molars, enamel hypoplasia, ectopic eruption of first molars, supernumerary teeth, and palatal displacement of maxillary canines) in an untreated orthodontic population, ages 7 to 14. The prevalence of associated tooth anomalies in seven groups of 100 subjects selected according to one primarily diagnosed dental anomaly was compared with the prevalence of the examined dental anomalies in a control group of 1,000 subjects. Significant reciprocal associations (p < 0.005) were found among five of the anomalies (aplasia of second premolars, small size of maxillary lateral incisors, infraocclusion of primary molars, enamel hypoplasia, and palatal displacement of maxillary canines), suggesting a common genetic origin for these conditions. Supernumerary teeth appeared to be a separate etiological entity with respect to all other examined tooth anomalies. The existence of associations between different tooth anomalies is clinically relevant, as the early diagnosis of one anomaly may indicate an increased risk for others.

Site-specificity of tooth agenesis in subjects with maxillary canine malpositions.

Tooth agenesis (hypodontia) was studied in two samples of nonsyndromic subjects possessing either maxillary canine-first premolar transposition (Mx.C.P1; N=43, M9:F34) or palatal displacement of the maxillary canine (PDC; N=58, M21:F37). Agenesis of permanent teeth was identified by x-ray film analysis. Significantly elevated tooth-agenesis frequencies were noted in both samples. Statistically significant differences between the Mx.C.P1 and PDC samples were found in locations of absent teeth, indicating site-specificity of tooth agenesis associated with these canine malpositions. In Mx.C.P1, agenesis of third molars (M3) occurred at a near-normal rate (19%) while maxillary lateral incisor (I2) agenesis showed a thirteen-fold increase (26%). In PDC, the prevalence rate for associated M3 agenesis was 40%, twice the normal rate, while I2 agenesis was 3%, a slight elevation of no statistical significance. These new findings may warrant a hypothesis of anteroposterior site-specific shift in the occurrence of tooth agenesis, associated genetically or epigenetically with distinct anomalies of maxillary canine position and possibly other abnormalities.

Dentoskeletal features associated with unilateral or bilateral palatal displacement of maxillary canines.

The aim of the present study was to analyze the prevalence and distribution of palatally displaced maxillary canines (PDC) in a large orthodontic population, and to investigate the associations between PDC, craniofacial features, and other dental anomalies such as aplasia or small-sized upper lateral incisors. An initial sample of 5000 subjects was evaluated. The reference values were calculated in a control group of 1000 subjects that was extracted from the initial sample. Chi-squared tests were used for statistical comparisons. The prevalence rate of PDC was 2.4%, with a male-to-female ratio of 1:3. PDC subjects with low angle vertical relationships showed a significantly high prevalence rate (60.2%). Unilateral PDC was significantly associated with aplasia of upper lateral incisors, whereas bilateral PDC was associated with aplasia of third molars. PDC showed reciprocal significant associations with bilateral small-sized upper lateral incisors. None of the three hypotheses offered in support of the "guidance theory" in the etiology of PDC were corroborated by the findings of the present study. The occurrence of other dental anomalies concurrent with PDC, sex differences, and the bilateral expression of PDC, all confirm the genetic component in the etiology of this tooth disturbance.

Mandibular lateral incisor-canine transposition, concomitant dental anomalies, and genetic control.

Mandibular lateral incisor-canine (Mn.I2.C) transposition is a rare developmental disturbance of tooth order characterized by positional interchange of the two teeth. In children with Mn.I2.C anomaly, the mandibular lateral incisor shows distal ectopic eruption and the adjacent canine subsequently erupts mesial to it. A sample of 60 orthodontic patients with Mn.I2.C transposition was studied using roentgenograms taken at the time of diagnosis. Two age-related phenotypes of the anomaly were identified: early-stage (median age, 9 years) and mature-stage (median age, 12 years). Mn.I2.C transposition occurred bilaterally in 10 subjects (17%) and favored female expression (sex ratio, M1:F3) and right-side occurrence (68% of unilateral cases). Statistically significant associations were found between Mn.I2.C transposition and increased frequency of tooth agenesis (M3, p < 0.01; MnP2, p < 0.01) and peg-shaped maxillary lateral incisors (p < 0.0001). The results from this study and the analysis of 50 previously published cases provide evidence that Mn.I2.C transposition is a disturbance of tooth order and eruptive position probably caused by genetic influences. The Mn.I2.C anomaly likely results from genetic mechanisms similar to those responsible for occurrences of its associated dental anomalies, such as tooth agenesis and peg-shaped maxillary lateral incisors. In an appendix, clinical orthodontic management of Mn.I2.C transposition is discussed, based on treatment data derived from the study sample.

Transposition of teeth and genetic etiology.

Twenty-one cases of transposition are presented showing a crude prevalence of 0.4%. A high rate of bilateral occurrence was seen. A significant number of cases were associated with other dental anomalies, such as peg-shaped lateral incisors and overretained deciduous teeth. Genetic etiology has been stressed and various other theories discussed.

Ectopic eruption of the maxillary first permanent molar. An epidemiological, familial, aetiological and longitudinal clinical study.

The aims of this thesis were to investigate the prevalence, familial tendency and aetiological factors of ectopic eruption of the maxillary first permanent molar, to analyse associations between ectopic eruption of the maxillary first permanent molar, to analyse associations between ectopic eruption of the maxillary first permanent molar and other tooth and developmental disturbances and cleft lip and/or palate defects, to make a longitudinal evaluation of the effects of orthodontic treatment in irreversible cases and of the prognosis for the atypically resorbed second primary molars in cases of reversible ectopic eruption and to carry out histological studies of second primary molars with extensive resorptions. The thesis is based on eight investigations. The subjects for the prevalence study consisted of 2,903 children. The main subjects in the clinical studies were the children with ectopic eruption of the maxillary first permanent molar from those children. The methods used were radiographic assessments, biometrics, orthodontic treatment, histology, different statistical methods and clinical assessments. The prevalence of ectopic eruption of the maxillary first permanent molar was found to be 4.3 per cent for the population and 21.8 per cent for cleft children. In sibs to children with ectopic eruption the prevalence was 19.8 per cent, indicating a genetic background. The main aetiological factors were the greater mesial angulation and the greater width of the ectopically erupted first permanent molar. In cases of reversible ectopic eruption the atypically resorbed second primary molars remained to the normal exfoliation time in 90 teeth out of 92. Treatment with cervical headgear in 46 children for an average of 9 months resulted in uprighting of the upper first permanent molars to good occlusion and in about 70 per cent of the children sufficient space for the second premolars. In the long-term follow-up, 10 years after treatment, two forms of discriminant analysis were used to evaluate the long-term treatment effects. The analyses showed a uniformity of the cases, indicating that the effects of the eruption disturbance had been corrected and all negative side effects of the treatment were eliminated.

Maxillary canine displacement and genetically determined predisposition to disturbed development of the dentition.

BACKGROUND: The relationship between maxillary canine displacement and the simultaneous occurrence of "genetically determined predisposition to disturbed development of the dentition" as defined by Hoffmeister was investigated in 675 patients. PATIENTS AND METHODS: Panoramic radiographs taken of each patient during the first and the second mixed dentition periods were evaluated. Canine inclination and the distance between the tip of the canine and a line connecting the cusps of the molars were computed in five different age groups according to Dausch-Neumann. RESULTS: Statistical analysis revealed 34 patients with "potential canine displacement", who exhibited further symptoms of "genetically determined predisposition to disturbed development of the dentition" significantly more frequently than the total group. The symptoms concerned were agenesia, displaced tooth buds, rotated or tilted incisors, aplasia and microdontia of lateral incisors. CONCLUSION: Careful follow-ups in patients with a predisposition to disturbed dental development enables risks to be anticipated and canine displacement to be detected at an early stage.