Introduction: Down syndrome people have special health care needs due to physical, medical, developmental, or cognitive conditions and require special considerations when receiving dental treatment. As a child or an adult, people with Down syndrome frequently visit a dental clinic because of the oro-dental, and craniofacial abnormalities they present. Published medical literature reported that tooth agenesis occurs more often in people with Down syndrome than in the general population. The study aims to describe and compare the prevalence of tooth agenesis, the number of missing teeth, and the type of teeth affected in a sample of 58 people confirmed with Down syndrome by cytogenetic testing.

Material and Methods: A total of 58 persons with Down syndrome needed dental care and treatment. None had previous orthodontic treatment. The dental findings were described by performing the complete extra- and intra-oral clinical examinations at Profiladent Clinic in Bucharest. For the assessment of tooth agenesis, a radiographic examination has been performed as well. All patients were able to cooperate for radiographic exams or panoramic radiographs, and no sedation was required. To select participants, we analysed medical records and cytogenetic profiles. 

Results: The prevalence of tooth agenesis among Down syndrome participants is 56.9%. Most affected individuals suffer only a mild form of tooth agenesis involving a small number of missing teeth (one or two). Some tooth types were more often missing than other ones. Excluding the third molar, upper lateral incisor and lower second premolars were most commonly missing teeth. Bilateral agenesis of upper lateral incisors occurred more often. There was no difference between the left and right sides of the jaw. Tooth agenesis occurred in different phenotypic patterns. Additional dental anomalies included microdontia, delays in development, delayed eruption, or taurodontism.

Conclusion: Down syndrome has tooth agenesis as one of its features. The severity of tooth agenesis varied from person to person. 

Keywords: Tooth Agenesis; Down’s Syndrome; Trisomy 21

Down’s syndrome (DS) is the most common and best known of all chromosomal syndromes [1]. The aetiology of Down syndrome is trisomy of all or part of chromosome 21, especially its long arm, in all or some of the body cells. Down syndrome people have special health care needs due to physical, medical, developmental, or cognitive conditions and require special considerations when receiving dental treatment [2]. Many of the medical and physiological features of Down syndrome have direct consequences for the oral health of persons affected and indirect consequences for the quality of life of persons with Down syndrome and their carers [3]. As a child or an adult, Down syndrome people frequently visit a dental clinic because of several oral-facial abnormalities and tooth anomalies they present. These include class III malocclusion, relative macroglossia, and delayed tooth eruption, missing teeth, microdontia, taurodontism, ectopic eruption and impaction of teeth. Due to compromised immune response, people with Down syndrome have an increased risk for periodontal disease as well. Published medical literature reported that absence of tooth development occurs more often in people with Down syndrome than in the general population [4]. Tooth agenesis may increase the risk for malocclusion, masticatory dysfunction, speech disorder, or aesthetic problems. The study aims to describe and compare the prevalence of tooth agenesis, the number of missing teeth, and the type of teeth affected in a sample of 58 people confirmed with Down syndrome by cytogenetic testing. Our study contributes to the literature by presenting individual phenotypic patterns of tooth agenesis in people with trisomy 21 and not only by describing the number or type of missing teeth.

A total of 58 Caucasian persons with Down syndrome (25 males and 33 females) needed dental care and treatment. To select participants, we analysed medical records and cytogenetic profiles. The participants, aged between 8-36 years, were enrolled in our study if they met the following criteria:

1. Having one or more missing teeth (excluding the third molar).
2. Cytogenetic diagnosis of trisomy 21.
3. Having no previous orthodontic, restorative, or prosthodontic treatment.
4. Adequate cooperation.
5. Mild cardiac problems.
6. Patients or parents/legal guardians were able to read and sign informed consent.

A 47 age and gender-matched healthy control participants have been included in the study as well. The dental findings were described by performing the complete extra and intra-oral clinical examinations at Profiladent Clinic in Bucharest. For the assessment of tooth agenesis, a radiographic examination has been performed as well. All patients were able to cooperate for radiographic exams or panoramic radiographs, and no sedation was required. The sample size was too small, and statistical analysis was not used. The Ethics Committee of the “Carol Davila” University approved the study clinical protocol.  The research was in full accordance with the World Medical Association Declaration of Helsinki. All the parents or legal guardians of the Down syndrome participants signed the informed consent form.

Results
Out of 58 subjects with Down syndrome, 33 (15 males and 18 females) experienced tooth agenesis meaning 56.9% of our patients. Tooth agenesis showed lower prevalence in the control group (4.3%) compared with the Down syndrome group. Due to an oral cavity with undersized bone structure and all permanent teeth developed, four Down syndrome participants (6.89%) presented dental crowding. 

1.    The number of missing teeth varied between 2 and 6 (hypodontia), showing mild to moderate levels of severity of the dental phenotype. The third molars were not considered. 
2.    Distribution of tooth agenesis by gender: no significant difference between the prevalence of tooth agenesis in males and females (Table 1).

Table 1: Distribution of tooth agenesis by gender.
3.    Tooth agenesis and type of teeth affected: upper lateral incisor (right lateral incisor) and lower second premolars (both right and left) were most commonly missing teeth. The second molars and central incisors were most rarely affected (Table 2).

Table 2: Distribution of tooth agenesis by the most frequent affected tooth group.
4.    Bilateral versus unilateral tooth agenesis: considering all missing teeth, a predominance of bilateral tooth agenesis was noted (Table 3).

Table 3: Prevalence rate of the most affected tooth group by the pattern of symmetry in the maxillary and mandible jaws.

5.    Distribution of missing teeth over maxilla/mandible: tooth agenesis does not seem to affect the maxilla and the mandible differently (Table 4).
6.    Distribution of missing teeth over left/right sides: no significant difference between the left and right sides of the jaw has been revealed (Table 4).

Table 4: Distribution of the most affected tooth group by localization in the maxillary and mandible jaws, right and left.
7.    Tooth agenesis occurred following an individual pattern of missing teeth (Figure 1-5) characterized by the different number or types of missing teeth involved and their combination.

Figure 1: Multiple tooth agenesis in an 8-year-old male patient with Down syndrome. (1,2,3) Examination of the dental arches reveals a mixed dentition, with a delayed tooth eruption pattern. (4) Panoramic radiograph showing the absence of both the lateral incisors in the maxillary arch and the agenesis of the lower right lateral incisor and the left central incisor. Moreover, the agenesis is associated with mesotaurodont first molars in both upper and lower arches * Position of the missing teeth.

Figure 2: A 28-year-old female patient with trisomy 21 presenting lower second premolars agenesis. Several dental anomalies are observed on the intraoral photos (1,2,3): upper diastema, maxillary lateral incisors microdontia, ectopic canines and spaced lower teeth. (4) Panoramic radiograph shows the absence of the lower second premolars and an agenesis diagnosis can be confirmed. * Position of the missing tooth.

Figure 3: Female patient aged 7 years old with confirmed trisomy 21 presenting all four second premolars agenesis. Intraoral photos (1,2,3) emphasize a mixed dentition with lack of space for the alignment of the permanent teeth. (4) Panoramic radiograph shows the congenital absence of the second premolars in both dental arches. * Position of the missing tooth.

Figure 4: A 13-year-old male with confirmed Down syndrome presenting different dental anomalies. (A) Mixed dentition with delayed eruption of permanent teeth, remarking the absence of the upper left lateral incisor. (B) Examination of the panoramic radiograph reveals the absence of the upper second premolar and of the maxillary left lateral incisor. * Position of the missing teeth.

Figure 5: Multiple tooth agenesis in a 14-year-old female patient with trisomy 21. (1-3) Intraoral photos reveal a mixed dentition, with the concomitant presence of the deciduous and permanent successor teeth at the level of the upper right canine, left lateral incisor and the lower canines. While on the upper arch, the right lateral incisor is missing and the contralateral one is microdont, in the lower arch there is only one incisor erupted. (4) Based on the anamnesis and the examination of the panoramic radiograph, it was confirmed the agenesis of the upper right lateral incisor, lower lateral incisors, and the lower right central incisor. Moreover, left second molars in both arches present an elongated pulp chamber and apically displaced furcation, which are specific for the diagnosis of taurodontism. * Position of the missing teeth.

The prevalence of permanent missing teeth is extensively studied because tooth agenesis affects more permanent dentition than deciduous one. The outcomes of our study support the higher prevalence of missing teeth in Down syndrome population than in general or healthy orthodontic population [4-10]. Depending on the sample size, the prevalence rate ranged from 38.6% [5] to 65% [10] or, even more, and 81% [4]. But in all cases, it was higher than in the general population. There is no relevant difference between the Down syndrome females’ group and Down syndrome males’ group regarding the prevalence of tooth agenesis. This finding agrees with that of other studies. [8,10-11] Suri et al. [7] reported prevalence rate higher in Down syndrome females compared to Down syndrome males. Russell et al. [4] reported a higher frequency of tooth agenesis in Down syndrome males than in females. The number of missing teeth varied from one person to another. None of our Down syndrome participants had more than six missing teeth. Our patients expressed mild to moderate forms of hypodontia. Kumasaka et al. [11] reported in a sample of 98 subjects with Down syndrome that 63% of them exhibited oligodontia. The small sample size included in our study may make it difficult to determine if our outcome is a correct finding or not. In a sample of 63 Down syndrome patients, van Marrewijk et al. [9] found hypodontia in 60% of the subjects.

Any tooth in the arch can be missing, but tooth agenesis tends to affect distinct tooth classes differentially [12]. However, some tooth types are more often missing than other ones. Our outcomes show that tooth agenesis involved most upper lateral incisor (right lateral incisor) and lower second premolars (both right and left). The second molars and central incisors were most rarely affected. Other studies reported similar data [6-8,13]. The data confirmed the general rule of end-of-series: if only one or a few teeth are missing, the absent tooth will be the most distal tooth of any given morphological class [14]. Our patients shared similar tooth agenesis features, but each of them had an individual phenotypic combination of missing teeth and other associated dental anomalies (more often localized form of microdontia and crowding of the teeth). Previous data reported similar results [15,16]. In 1959, Lejeune et al. determined the third chromosome 21 as cause of Down syndrome. So far it is unknown how can arise Down syndrome phenotype, including dental anomalies, from trisomy in chromosome 21. The extra copies of genes on chromosome 21 disrupts the course of normal development, causing the characteristic features of Down syndrome and the increased risk of health problems associated with this condition. However, a direct genotype-phenotype correlation is still unclear. The small acrocentric chromosome 21 likely contains 200 to 300 genes, and their protein products may influence gene products and their function on heterologous chromosomes [17].  How the expression levels of these genes are altered by the presence of the third copy of chromosome 21 is still a challenge.

Due to their complex pathology (dysmorphic features and delayed psychomotor development) persons with Down syndrome should be monitored by a multidisciplinary team. Dental professionals have an important role to improve as much as possible oral health. They should timely recognise the distinctive clinical dental phenotype and natural history of Down syndrome. They should be trained to care for those with special needs, such as Down syndrome people. Routine dental visits are needed, and timely dental protocols of tooth agenesis require careful multidisciplinary planning to improve oral functions and prevent or minimise complications due to their medical condition.

Down syndrome presents tooth agenesis as one of its features. The severity of tooth agenesis varied from person to person. 

Conflicts of Interest
The authors declare that they have no conflict of interest.

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Corresponding Author: Dr. Emilia Severin, Genetics Department, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.

Copyright: © 2021 All copyrights are reserved by Emilia Severin, published by Coalesce Research Group. This This work is licensed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited.