Abstract
Oral health in Down Syndrome (DS) individuals has some peculiar aspects that must be considered in the follow up of these patients. In this chapter, we will focus on the oral and maxillofacial morphological alteration, the most prevalent oral pathologies as well as preventive measures and strategies for pathologies management in this population. Also, future research on oral health of DS will be discussed.
Keywords
- Down syndrome
- caries
- periodontitis
- saliva
- microbiological and biochemical parameters
- maxillary treatment
- otorhinolaryngology
- airway obstruction
- pacifier-shaped device
1. Introduction
The skeletal and soft tissue features associated to DS individuals may contribute to increased drooling, angular cheilitis, dry mouth, and an increased prevalence and severity of fissured tongue and lower lips.[1-4] Bruxism (tooth-grinding) is a behavioural manifestation displayed by some DS individuals that may further contribute to alterations in tooth morphology and mineralization.[5-7]
Also, DS individuals have a significantly higher prevalence of some oral diseases, including periodontal disease, which develops at early age and is rapidly progressive as well as oral candidosis. [8-10] On the other hand, a lower prevalence of dental caries appears to be a characteristic of DS populations, although there are some controversial results.[11-15] The alteration in oral microbiology and biochemistry of DS population will be discussed in the light of these infectious diseases.[11]
However, the oral health problems experienced in people with DS are still not fully defined, so future studies are suggested.
2. Materials and methods
Bibliographic research undertaken through the MEDLINE/PubMed, Science Direct and B-on search engine as well as through the library archives of Porto University’s School of Dental Medicine between 1988 and 2014 limited to articles published in English, French, Spanish and Portuguese. In total, 63 bibliographic references were obtained according to the following factors of inclusion: articles released by Porto University’s School of Dental Medicine’s servers through SCOPUS, ISI, Cochrane and PUBMED database, articles with titles referred in the keywords mentioned above.
3. Results and discussion
3.1. Maxillofacial and oral morphological features
Patients with DS have a high prevalence of specific otorhinolaryngologic pathology, including recurrent sinusitis and chronic nasal obstruction, as a consequence of hypotonia and craniofacial malformations (Figure 1.).[16-20]
The base of the skull, the frontal bone and the paranasal sinus are significantly small, leading to a decrease in the size of the sella turcica. There’s a flattening of the cranial base as a result of vertical hypoplasia of the structures of the skull (Figure 1.).[2, 9, 17, 21]
These problems, together with their short Eustachian tubes, predispose them to chronic media otitis with effusion and conductive hearing loss, which interferes with their language acquisition. They are also more susceptible to recurrent infections, particularly of the upper airway.[16-20]
Sleep apnea is diagnosed in more than 50% of the patients and may adversely affect behaviour, growth and neurodevelopment.[16, 20]
Another common abnormality is the dysfunction of the thyroid gland. Individuals with DS tend to present hypothyroidism and it is related to an underdevelopment of the bones and the teeth and to a delayed tooth eruption.[1, 2] The atlanto-axial joint, which is responsible for promoting communication between the first and the second vertebrae, is unstable in about 20% of the individuals.[1, 2] This defect may cause spinal cord compression during sudden movements of flexion and extension and, therefore, the dentist must be very careful while handling their necks.[1, 2]
When compared to the general population, these children have up to 20 times higher risk of developing leukaemia.[1, 2] The dentist should be alert to the presence of persistent lesions and spontaneous gingival bleeding as it may be an early sign of leukaemia.[3]
Mental health and behavioural problems, including attention deficit disorder, hyperactivity, obsessive-compulsive disorder and depression are common among individuals with DS.[9, 21, 22] Most of them also develop Alzheimer’s disease around the fourth or fifth decade of life.[1, 2] This degenerative disease is related to an over-expression of β-amyloid precursor protein (βAPP), which is the expression of one of the triplicated genes in DS.[1, 2, 9] The most common craniofacial features observed in children with DS are small nose, low nasal bridge, narrow, short, deep and high palate, bifid uvula, hypertrophy of the tonsils, underdeveloped jaw, cleft lip, incomplete lip closure, hypotonic lips, fissured tongue, inaccurate and slow tongue movement, anterior open bite, posterior crossbite and reductions in the maxillary arch and changes in temporary and permanent tooth eruption (Figure 2., Figure 3., Figure 4., Figure5.).[6, 7, 9, 16, 17, 20, 23, 24]
This hypotonicity is associated with ligament laxity, easily visible throughout the body. It induces hyper-flexible joints, which can compromise the periodontal ligaments.[20] Excess of saliva on the labial commissure is also related to the muscle hypotonicity and can lead to irritation, cracking (angular cheilitis), aphthous ulcers and infectious conditions like candidiasis.[3, 24]
According to [Oredugba (25)], 51% of class I dental malocclusion and 47% of class III among 43 individuals with DS and only 5% of class III in the control group (individuals without DS), concluding that class III has a higher incidence in DS individuals than in the general population.
[Musich (26)] and [Soares K (27)] have concluded that class III is more frequent in DS individuals. Anatomically, the facial mid-third is underdeveloped but the mandible follows normal development (pseudo-progeny). This midface dysplasia also contributes to the narrow maxilla (Figure 5., Figure 6.).[7, 11, 18, 20]
Mandible measurements are not significantly different from normal subjects. However, a transverse expansion may occur due to lingual pressure.[20, 28] This intermaxillary discrepancy prevents the optimal intercuspal position to occur, which is needed to stabilize the mandible and the hyoid bone during mastication and swallowing.[16, 20]
Anterior crossbite is primarily attributed to the anteroposterior deficiency of the maxillary arch development, resulting in a crossbite of the mandible, projecting the jawbone arch towards the front of the maxilla (Figure 5., Figure 6.).[5, 6, 26-29]
Dental anomalies are very common, both in the primary and permanent teeth and occur with an incidence five times greater in DS individuals than in general population (Figure 7.).[7, 23]
Anomalies in the number (fewer), size (smaller) and morphology (crowns may also be short, small and conical) and the timing of their development (late dentition) are constant features of this syndrome.[7, 23] In the primary dentition, the most commonly absent teeth are lateral incisors, while in the permanent dentition, third molars, second premolars and lateral incisors, in this sequence, are the most frequently missing teeth (Figure 7.). [3, 7, 20]
Patients with DS have complete tooth mineralization, delayed tooth eruption (six to eighteen months) changes in the sequence of eruption (mainly of the temporary teeth), high incidence of impacted teeth (incisors and canines) and teeth agenesis. Microdontia, enamel hypoplasia, hypodontia of deciduous teeth and oligodontia are the most common dental anomalies. Structural abnormalities include taurodontia, peg-shaped teeth, fusion and germination. Canines are the most affected regarding shape and size.[3, 11, 20, 29, 30]
3.2. Oral pathology
3.2.1. Caries
A majority of published studies have reported that people with DS have lower caries rates than people without DS, although several studies found that people with and without DS share the same caries rates, and some reported higher caries rates in those with DS.[7, 13, 14, 31] The differences herein described may be related to the control group used in each study: non-related healthy individuals, healthy siblings or other cognitive impaired individuals. The most commonly used indicator of caries experience is an index comprising disease and treatment markers, the DMFT (Decayed, Missing and Filled Teeth).[11, 12, 14] This index should be analysed together with factors such as a diet, frequency of snacking, social status, oral health in close relatives, dental awareness and past dental history. In studies of
Saliva plays a crucial role in the defense against periopathogenic and cariogenic bacteria in the oral cavity and the equilibrium between demineralisation and remineralisation of enamel and dentin.[3, 12, 38] Consequently, the protective effects of salivary constituents, salivary flow rates and the salivary buffering capacity are essential.[36, 39-43] It is agreed almost universally that the salivary flow rate is significantly reduced in individuals with Down syndrome.[13, 36, 39-43] Also,
3.2.2. Periodontal disease
The Gingivitis and Periodontitis are the two main subgroups of periodontal diseases affecting a high percentage of the world population and is therefore a serious public health problem.[8] Dental practitioners are challenged by the high incidence of early-onset aggressive periodontal disease in DS; these patients have higher levels of periodontal pathogens and periodontitis-associated interproximal bone loss. The complex anatomy, physiology, immunology and microbiology underscore the need for further investigation in specific areas related to dental treatment of these patients.[8, 48, 49] Gingivitis and periodontal disease start early in life, and the severity of these diseases increase with age. The prevalence of periodontal disease in adolescents with DS is 30% to 40%. Consequently, a large number of young people with DS lose their permanent anterior teeth in their early teens. In individuals in their thirties, the incidence of periodontal disease rises up to nearly 100%.[8]
3.2.3. Bruxism
Bruxism is quite common in this population, initiating at very young age, and often persisting throughout life. [5] The increased frequency of bruxism in DS population is associated to chronic anxiety, underdeveloped nervous system, malocclusion and TMJ dysfunction due to hypotonicity, hyper flexibility and laxity of the supporting ligaments. Initially, it creates an erosion of the pits and fissures of the occlusal surfaces (that become smoother), enabling self-cleaning with tongue and facilitating oral hygiene. [5, 11, 14] On the other hand, it can lead to an overloading of the supporting tissues and subsequent teeth fractures. These patients should be monitored through a regular program to allow an early diagnosis of the problems related to bruxism. [5, 14] In cases where bruxism is diagnosed, it is necessary to reposition the jaw and to decrease teeth grinding. Unfortunately, patients with a severe bruxism are the ones with more neurological problems and the treatment may not be successful.[5, 52]
3.3. Preventive and therapeutic intervention
This section intends to guide clinicians regarding the most important preventive measures in this population and also suggest the best approaches to improve the most common oral pathologies in DS individuals.[48] In this regard, oral hygiene and habits will be discussed and specific methods such as adapted DS pacifiers and rapid maxillary expansion will be suggested. According to
3.4. Palatal plates
To improve the suction, drooling and the chewing and secondarily to help the development of the language,
After 12 months of therapy, the mean duration of the factor "closed mouth” was significantly longer (p < 0.001) and "inactive protrusion of the tongue” significantly shorter (p < 0.001) in the test group than in the control group. The results indicate that in children with Down syndrome, palatal plate therapy may be a valuable complement to a training program for improving orofacial muscle function. It may be used as a prophylactic measure of the tongue protrusion.
Undesirable effects after the insertion of the plate can occur; for example, development of active avoidance of the plate with the tongue, which results in more pronounced tongue protrusion, no clinical reaction, immediate habituation to the plate, hyper salivation or more pronounced tongue protrusion after the suspension of the treatment, even if for a short period.[57-62] All these reactions were rare, but required fitting a new plate, or suspension of the treatment.
Due to the presence of a protruding tongue and a muscular hypotonicity, these children have oral–motor problems (seen during swallowing, chewing and sucking) and are mouth breathers (exhibit open bite). The use of an adapted pacifier could prevent these problems (Figure 9).[3, 7, 11, 20]
When teeth are erupting, the plate does not adhere to the palate. So, they take off the plate easily, which leads to stopping the usage of the plate for a period until the child is about 3 years old. When the device is omitted for a period of time in the early stages of treatment, it will result in a return to the pathological condition. It is important to notice that people that already use the plates on their patients, don’t refer major problems. Do not put plates if there is not a strong motivation by the parents. The motivation of the parents is fundamental.[57-62]
Due to fear of plate swallowing and child choking, the plate developed by Castillo-Morales did not allow a prolonged use and required adult supervision [58]. Thereafter, Andrade C. et al [20, 63] developed a modified, pacifier-shaped device, that provide greater security, prolonged usage time (even at night), less concern by caregivers, and better acceptance by society. The results of its use show an improvement in aesthetics with less tongue protrusion and higher time of closed mouth when compared to the traditional Castillo-Morales plate (Figure 11., Figure 12., Figure 13.).[12, 20, 58, 63]
3.5. Fixed appliances
We can place fixed appliances in preschool age, if the child is cooperative. Problems like anterior or posterior crossbites should be corrected as soon as they are found. Fixed appliances have better results because we can have a greater control of their use, which does not happen with removable appliances, which can either be used or not. We may expand the maxilla to gain more space to the tongue and in DS we prefer to do it expanding from the apical base, to obtain an orthopaedic effect. At certain ages, the effects of maxillary disjunction may be more favourable, which has to do with the overall growth of the jaws and the individual himself (Figure 13., Figure 14.). [20, 28]
Advantages of the device
Fixed appliance
Easy to clean
Acts in a short time
Does not need intense cooperation from parents or from the children.
Cutting this cycle of mouth breathing and increasing the area for nasal ventilation can provide a solution for some breathing difficulties, a reduction of tongue protrusion and drooling, as well as the high incidence of repeating respiratory infections and the high rates of compression and crossbites.[20, 28]
After the maxillary disjunction and in respect to clinical symptomatology, we may conclude:
Nasal symptomatology:
Global improvement of cases and controls, but in that the cases show up, markedly, a minor incidence of rhinorrhea: "went the first summer in that my son had the nose completely without secretions".
Otologic symptomatology:
Smaller evidence in the resolution from the serous otitis, that persisted in the cases and in the controls.
Rapid maxillary expansion produced a significant augmentation of nasal volume in children who had been treated (p<0.05) compared to the control group; these results were stable through the period of retention.
The rapid maxillary expansion (disjunction) in infants with Down syndrome:
Diminishes the number of infections of the superior airways.
Improves nasal permeability.
Improves several parameters analysed by speech therapists.
Tongue Mobility
Articulation
Intelligibility
Rapid maxillary expansion (RME) increased space for the tongue in the oral cavity (Figure 15., Figure 16., Figure 17.). This in turn results in a reduction of tongue protrusion and drooling. These aspects, in addition to the enlargement of the maxilla, often lead to an aesthetic improvement noted by the parents of the RME children. By placing the tongue in its normal position, the speech is improved, and so the aesthetics and self-confidence of the individual, facilitating his integration in society. This procedure may be carried out concomitantly with other surgical procedures for upper airway obstruction, sleep apnea and chronic otitis media with effusion. Rapid maxillary expansions give these patients a better airway, if used (Figure 15., Figure 16., Figure 17.). It is important to make exercise routines and teach these patients to use this new airway, increasing attention and activity, and leading to a better general development, better general health and less hours of work lost by the family. The indications should be accurate. The effect is similar to the infants from the general population. The use of this device should be included in the suggestion to medical and connected Associations of parents of Down’s syndrome children.
We should not be afraid to use facial masks or other orthodontic devices because these patients are very supportive, and we should encourage all dentists to treat these patients.
We cannot forget that all cases must have an appropriate fixed orthodontic contention, in most times for life.The orthodontic retention phase minimises unwanted dental movements and maintains the corrections, and in these cases, most of the times, a fixed contention is necessary because hypotonia and deleterious habits are very dangerous for the stability of the correction (Figure 18., Figure 19., Figure 20., Figure 21.). [20, 28]
4. Conclusion
Patients with Down syndrome present peculiar orofacial features that, when not corrected, may interfere with their physical, psychological and social development.
Children with this syndrome have a high risk of developing malocclusion and periodontal problems, and these should be the main concerns in their treatment needs. When planning the dental treatment of patients with Down syndrome, dental practitioners should always consider their general health, in order to achieve a holistic and interdisciplinary approach. Nevertheless, there is a need to improve the oral health services available to individuals with DS, to further investigate the interrelations between all their health problems, and to provide a higher level of information to parents of DS.
References
- 1.
Klug WS, Cummings MR, Spencer CA. Concepts of Genetics. Pearson Education, Upper Saddle River; 2006. - 2.
Lewis R. Human Genetics Concepts and Applications, 7th ed. McGraw-Hill, New York; 2007. - 3.
Shore S, Lightfoot T, Ansell P. Oral disease in children with Down syndrome: Causes and prevention. Community practitioner: The journal of the Community Practitioners’ & Health Visitors’ Association. 2010;83(2):18–21. - 4.
Mouradian WE. The face of a child: Children’s oral health and dental education. Journal of dental education. 2001;65(9):821–31. - 5.
Macho V, Andrade D, Areias C, Norton A, Coelho A, Macedo P. Prevalência de hábitos orais deletérios e de anomalias oclusais numa população dos 3 aos 13 anos. Rev port estomatol med dent cir maxilofac. 2012;53(3):143–7. - 6.
Macho V, Seabra M, Pinto A, Soares D, Andrade A. Alterações craniofacial e particularidades orais na Trissomia 21. Acta Pediatr Port. 2008;39(5):190–4. - 7.
Macho V. Caracterização de uma população pediátrica com Trissomia 21: FMD-UP; 2007. - 8.
Cichon P, Crawford L, Grimm WD. Early-onset periodontitis associated with Down’s syndrome—Clinical interventional study. Annals of periodontology/the American Academy of Periodontology. 1998;3(1):370–80. - 9.
Moreira Lília MA. A síndrome de Down e sua patogénese: Considerações sobre o determinismo genético. Rev Bras Psiquiatr. 2000;22(2):96–9. - 10.
Martinez-Martinez RE, Loyola-Rodriguez JP, Bonilla-Garro SE, Patino-Marin N, Haubek D, Amano A, et al. Characterization of periodontal biofilm in Down syndrome patients: A comparative study. The journal of clinical pediatric dentistry. 2013;37(3):289–95. - 11.
Areias C. Efeito da composição da saliva na prevalência cárie dentária em crianças com trissomia 21: Universidade do Porto Faculdade de Medicina Dentária; 2011. - 12.
Vicente VA. Relação entre a prevalência da doença cárie e risco microbiológico. Cienc Odontol Bras. 2008;11(2):44–8. - 13.
Areias C, Sampaio-Maia B, Pereira Mde L, Azevedo A, Melo P, Andrade C, et al. Reduced salivary flow and colonization by mutans streptococci in children with Down syndrome. Clinics. 2012;67(9):1007–11. - 14.
Areias CM, Sampaio-Maia B, Guimaraes H, Melo P, Andrade D. Caries in Portuguese children with Down syndrome. Clinics. 2011;66(7):1183–6. - 15.
Holst D, Schuller AA, Aleksejuniene J, Eriksen HM. Caries in populations—A theoretical, causal approach. European journal of oral sciences. 2001;109(3):143–8. - 16.
Moura CP. Trissomia 21-Perspectiva Otorrinolaringológica. Arquivos de Medicina. 2004;18, 1/2: 61 - 65. - 17.
Jacobs I, Gray RF, Todd N. Upper airway obstruction in children with Down syndrome. Arch Otolaryngol Head Neck Surg. 1996;122:945–50. - 18.
Moura CP, Andrade D, Cunha LM, Tavares MJ, Cunha MJ, Barros H, Pueschel SM, Vaz P, Clemente MP. Down syndrome: Otolaryngological effects of rapid maxillary expansion. The journal of laryngology & otology. 2008;12(122):1318–24. - 19.
de Moura CP, Andrade D, Cunha LM, Tavares MJ, Cunha MJ, Vaz P, et al. Down syndrome: Otolaryngological effects of rapid maxillary expansion. The journal of laryngology and otology. 2008;122(12):1318–24. - 20.
Andrade DJ. Trissomia 21 – Estudo Dento-Maxilo-Facial FMD-UP; 2000. - 21.
Fernandes A, Mourato P, Xavier M, Andrade C, Fernandes C, Palha M. Caracterização da evolução somática de crianças portuguesas com trissomia 21 – resultados preliminares. Acta Pediatr Port. 1998;29:261–8. - 22.
Lewis CW, Grossman DC, Domoto PK, Deyo RA. The role of the pediatrician in the oral health of children: A national survey. Pediatrics. 2000;106(6):E84. - 23.
Acerbi AG, de Freitas C, de Magalhaes MH. Prevalence of numeric anomalies in the permanent dentition of patients with Down syndrome. Special care in dentistry: Official publication of the American Association of Hospital Dentists, the Academy of Dentistry for the Handicapped, and the American Society for Geriatric Dentistry. 2001;21(2):75–8. - 24.
Allison PJ, Hennequin M. The oral assessment in Down syndrome questionnaire (OADS): Development of an instrument to evaluate oral health problems in individuals with Down syndrome. Community dental health. 2000;17(3):172–9. - 25.
Oredugba FA. Oral health condition and treatment needs of a group of Nigerian individuals with Down syndrome. Down’s syndrome, research and practice: The journal of the Sarah Duffen Centre/University of Portsmouth. 2007;12(1):72–6. - 26.
Musich DR. Orthodontic intervention and patients with Down syndrome. The angle orthodontist. 2006;76(4):734–5. - 27.
Soares K, Mendes R, Junior R, Rosa L, Costa K. Prevalência de maloclusão em portadores de Síndrome de Down na cidade de Teresina-PI. Revista Gaúcha de Odontologia. 2009;57:187–91. - 28.
de Moura CP, Vales F, Andrade D, Cunha LM, Barros H, Pueschel SM, et al. Rapid maxillary expansion and nasal patency in children with Down syndrome. Rhinology. 2005;43(2):138–42. - 29.
Macho V, Coelho A, Areias C, Macedo P, Andrade D. Craniofacial features and specific oral characteristics of Down syndrome children. Oral health and dental management. 2014;13(2):408–11. - 30.
Allison PJ, Hennequin M, Faulks D. Dental care access among individuals with Down syndrome in France. Special care in dentistry: Official publication of the American Association of Hospital Dentists, the Academy of Dentistry for the Handicapped, and the American Society for Geriatric Dentistry. 2000;20(1):28–34. - 31.
Law V, Seow WK, Townsend G. Factors influencing oral colonization of mutans streptococci in young children. Australian dental journal. 2007;52(2):93–100; quiz 59. - 32.
Fung K, Allison PJ. A comparison of caries rates in non-institutionalized individuals with and without Down syndrome. Special care in dentistry: Official publication of the American Association of Hospital Dentists, the Academy of Dentistry for the Handicapped, and the American Society for Geriatric Dentistry. 2005;25(6):302–10. - 33.
Fung K, Lawrence H, Allison P. A paired analysis of correlates of dental restorative care in siblings with and without Down syndrome. Special care in dentistry: Official publication of the American Association of Hospital Dentists, the Academy of Dentistry for the Handicapped, and the American Society for Geriatric Dentistry. 2008;28(3):85–91. - 34.
Gizani S, Papaioannou W, Haffajee AD, Kavvadia K, Quirynen M, Papagiannoulis L. Distribution of selected cariogenic bacteria in five different intra-oral habitats in young children. International journal of paediatric dentistry/the British Paedodontic Society [and] the International Association of Dentistry for Children. 2009;19(3):193–200. - 35.
Tenuta LM, Ricomini Filho AP, Del Bel Cury AA, Cury JA. Effect of sucrose on the selection of mutans streptococci and lactobacilli in dental biofilm formedin situ. Caries research. 2006;40(6):546–9. - 36.
Areias C, Sampaio-Maia B, Macho V, Leal I, Melo P, de Andrade C. Does the chemistry in the saliva of Down syndrome children explain their low caries prevalence? European journal of paediatric dentistry: Official journal of European Academy of Paediatric Dentistry. 2013;14(1):23–6. - 37.
Catarina Barbosa JM, Milagre V, Andrade D, Areias C. Inhalation conscious sedation with nitrous oxide/oxygen in pediatric dentistry. MEDICALEXPRESS. 2014 Jun;1(3):102-104 - 38.
Schaff-Blass E, Rozier RG, Chattopadhyay A, Quinonez R, Vann WF, Jr. Effectiveness of an educational intervention in oral health for pediatric residents. Ambulatory pediatrics: The official journal of the Ambulatory Pediatric Association. 2006;6(3):157–64. - 39.
Siqueira WL, Bermejo PR, Mustacchi Z, Nicolau J. Buffer capacity, pH, and flow rate in saliva of children aged 2-60 months with Down syndrome. Clinical oral investigations. 2005;9(1):26–9. - 40.
Siqueira WL, de Oliveira E, Mustacchi Z, Nicolau J. Electrolyte concentrations in saliva of children aged 6–10 years with Down syndrome. Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics. 2004;98(1):76–9. - 41.
Siqueira WL, Nicolau J. Stimulated whole saliva components in children with Down syndrome. Special care in dentistry: Official publication of the American Association of Hospital Dentists, the Academy of Dentistry for the Handicapped, and the American Society for Geriatric Dentistry. 2002;22(6):226–30. - 42.
Siqueira WL, Siqueira MF, Mustacchi Z, de Oliveira E, Nicolau J. Salivary parameters in infants aged 12 to 60 months with Down syndrome. Special care in dentistry: Official publication of the American Association of Hospital Dentists, the Academy of Dentistry for the Handicapped, and the American Society for Geriatric Dentistry. 2007;27(5):202–5. - 43.
Vijayaprasad KE, Ravichandra KS, Vasa AA, Suzan S. Relation of salivary calcium, phosphorus and alkaline phosphatase with the incidence of dental caries in children. Journal of the Indian Society of Pedodontics and Preventive Dentistry. 2010;28(3):156–61. - 44.
Lenander-Lumikari M, Loimaranta V. Saliva and dental caries. Advances in dental research. 2000;14:40–7. - 45.
Davidovich E, Aframian DJ, Shapira J, Peretz B. A comparison of the sialochemistry, oral pH, and oral health status of Down syndrome children to healthy children. International journal of paediatric dentistry/the British Paedodontic Society [and] the International Association of Dentistry for Children. 2010;20(4):235–41. - 46.
Kavanagh DA, Svehla G. Variation of salivary calcium, phosphate and buffering capacity in adolescents. Archives of oral biology. 1998;43(12):1023–7. - 47.
Lee SR, Kwon HK, Song KB, Choi YH. Dental caries and salivary immunoglobulin A in Down syndrome children. Journal of paediatrics and child health. 2004;40(9–10):530–3. - 48.
Cristina Areias VM, Coelho A, Pereira L, Andrade D, Pérez-Mongiovi D, Sampaio-Maia B. Enfoque clínico de niños con síndrome de Down en el consultorio dental. Avances en odontoestomatologia. 2014;(6):307-313. - 49.
Tanaka MH, Rodrigues TO, Finoti LS, Teixeira SR, Mayer MP, Scarel-Caminaga RM, et al. The effect of conventional mechanical periodontal treatment on red complex microorganisms and clinical parameters in Down syndrome periodontitis patients: A pilot study. European journal of clinical microbiology & infectious diseases: Official publication of the European Society of Clinical Microbiology. 2015 Mar;34(3):601-8. doi: 10.1007/s10096-014-2268-7. Epub 2014 Nov 4. - 50.
Cornejo LS, Brunotto M, Hilas E. Salivary factors associated to the prevalence and increase of dental caries in rural schoolchildren. Revista de saude publica. 2008;42(1):19–25. - 51.
Hennequin M, Allison PJ, Veyrune JL. Prevalence of oral health problems in a group of individuals with Down syndrome in France. Dev Med Child Neurol. 2000;42(10):691–8. - 52.
Martín M, Vasquez E, Diz P, Figueiral H, Vasconcelos L, Figueiredo J, Andrade D. Terapia de Estimulação Orofacial: Princípios e Considerações. Revista de Saúde Oral Revista de Saúde Oral. 1996;1:51–4. - 53.
Macho V, Palha M, Macedo AP, Ribeiro O, Andrade C. Comparative study between dental caries prevalence of Down syndrome children and their siblings. Special care in dentistry: Official publication of the American Association of Hospital Dentists, the Academy of Dentistry for the Handicapped, and the American Society for Geriatric Dentistry. 2013;33(1):2–7. - 54.
Macho V, Seabra M, Areias C, Ribeiro O, Andrade C. Comparação dos cuidados de saúde oral numa população com trissomia 21 e seus irmãos. Comparação dos cuidados de saúde oral numa população com trissomia 21 e seus irmãos. JADA. 2008;8(5):2-14. - 55.
Fischer-Brandies H, Limbrock GJ, Tragner-Born J. La Thérapie Fonctionnelle Sensorimotrice des Troubles Fonctionnels Oro-Faciaux Chez les Enfants avec I.M.C., d’après Castillo-Morales (Infirmité motrice cérébrale). L’orthodontie Française. 1988;59 Pt 2:449-58. - 56.
Chung MH, Kaste LM, Koerber A, Fadavi S, Punwani I. Dental and medical students’ knowledge and opinions of infant oral health. Journal of dental education. 2006;70(5):511–7. - 57.
Carlstedt K, Dahllöf G, Nilsson B, Modeer T. Effect of palatal plate therapy in children with Down syndrome. A 1-year study. Acta Odontol Scand. 1996;54(2):122–5. - 58.
Castillo-Morales R, Avalle C, Schmid R. Possibilità di Trattamento della Patologia Orofaciale nella Sindrome di Down con la Placa di Regolazione Motoria. Pediatria Preventiva e Sociale. 1984;34:1–4. - 59.
Limbrock GJ, Castillo-Morales R, Hoyer H, Stover B, Onufer C. Castillo-Morales approach to orofacial pathology in Down syndrome. International journal of orofacial myology. 1993 Nov;19:30-7. - 60.
Limbrock GJ, Fischer-Brandies H, Avalle C. Castillo-Morales’ orofacial therapy: Treatment of 67 children with Down syndrome. Developmental medicine and child neurology. 1991;33:296–303. - 61.
Limbrock GJ, Hoyer H, Scheying H. Regulation therapy by Castillo-Morales in children with Down syndrome: Primary and secondary orofacial pathology. Journal of dentistry for children. 1990 Nov-Dec;57(6):437-41. - 62.
Hoyer H, Limbrock GJ. Orofacial regulation therapy in children with Down syndrome, using the methods and appliances of Castillo-Morales. Journal of dentistry for children. 1990;Nov–Dec:442. - 63.
Andrade C, Tavares P, Rebelo P, Palha M, Tavares M. Placa modificada para tratamento de hipotonia oro-muscular em crianças com idade compreendida entre os 2 meses e os 2 anos. Ortodontia. 1998;3(2):111–7.