Oral findings in children and adolescents with Prader-Willi syndrome

The study included 80 patients at the age between 2.5 and 17.2 years (41 boys and 39 girls): 40 with Prader-Willi syndrome (PWS group) reporting for their routine checkups at Clinic of Endocrinology and Diabetology, Children’s Memorial Health Institute, and 40 healthy individuals (controls) reporting for their checkups at the Department of Paediatric Dentistry, Warsaw Medical University. Studies were performed after a written consent of the patients and/or their parents/legal guardians. Bioethics committee had been obtained. The control group was age- and sex-matched to the PWS group. Exclusion criteria from both groups were as follows: lack of cooperation with the dentist, cigarette smoking, and orthodontic treatment. Patients with obesity and chronic diseases or who are receiving chronic treatment were excluded from the control group, whereas patients with gastroesophageal reflux disease were excluded from the PWS group.

Table 1 presents characteristics of patients with regard to the type of dentition. Thirty-nine patients with PWS were included in the National Health Service (NHS) Growth Hormone Program (the inclusion criteria were rehabilitation, lack of obesity < 97 centile, low-calorie diet, balanced carbohydrate metabolism, absence of other contraindications to growth hormone therapy). One patient with PWS was obese. Obesity was not present in the control group.

A case-control study was performed in a dental office and included an analysis of medical documentation and an interview with the patient and/or parents/legal guardians (presence of systemic diseases, applied medicinal products, oral para-functional habits), dental examination, and assessment of physical and chemical parameters. General health status of PWS patients was assessed by a pediatrician from the Clinic of Endocrinology and Diabetology.

The study was conducted by two dental surgeons with clinical experience in children dentistry longer than 5 years, after the Cohen’s kappa coefficient was calibrated and the value of 0.8 was achieved. The following were assessed: teeth grinding and mouth breathing, presence of tooth wear, hygiene status according to the Silness and Löe Plaque Index and gingival status according to Gingival Index with regard to six index teeth: 16, 12, 24, 36, 32, and 44 (in the deciduous dentition: 55, 51, 63, 75, 71, and 83), localization of gingivitis, and presence of periodontal pockets [18]. Pocket depths (only around permanent first molars and incisors) were recorded for children over the age of 12. The WHO 621 probe with a 0.5-mm ball end and black band at 3.5 to 5.5 mm was used [19].

The presence of tooth wear was assessed on the labial, incisal, and palatal/lingual surfaces of the six upper and lower anterior teeth and on the occlusal surfaces of all four permanent first molars (mixed and permanent dentition) or second primary molars (deciduous dentition). Surfaces were scored in accordance with the Smith and Knight Tooth Wear Index modified by Bardsley et al. [20, 21]. Dentine exposure (score 1—the dentine is just visible (including cupping) or dentine exposure of less than a third of the surface, and score 2—dentine exposure greater than a third of the surface) and exposure of pulp or secondary dentine (score 3—exposure of pulp or secondary dentine) were taken into account. Injuries due to orthodontic appliances and surfaces destroyed by dental caries or with fillings were not included.

The Saliva-Check Buffer Test, GC Co., Tokyo, Japan, was used for saliva tests [8, 22, 23]. The assessment was done according to the manufacturer’s instruction. Saliva tests were performed in the morning at least 2 h after breakfast. Patients did not brush their teeth or use a mouthwash for at least 1 h. The following elements are assessed:

Saliva secretion was stimulated by chewing paraffin tablets. Every 30 s, patients were asked to expectorate the saliva into a graduated test tube. Saliva was being collected for exactly 5 min.

Teeth grinding is the main etiological factor of tooth wear. However, in our study, this symptom was reported more rarely than tooth wear. In the studies by Saeves et al. in a group of 49 patients with PWS at the age of 6.5–40.9 years, the frequency of teeth grinding in PWS (36.7%) was also lower than tooth wear (89.8%) [6]. It seems that the incidence of teeth grinding was underestimated by parents of subjects. PWS patients often suffer from sleep apnea and they have emotional and behavioral problems, e.g., overeating, difficulty with routine change, temper tantrums, mood fluctuations, aggression, and auto-aggression. These factors are suggested to be involved in the precipitation of bruxism [24]. On the other hand, higher prevalence of tooth wear compared to teeth grinding may emphasize the importance of others factors, e.g., exposure of teeth tissues to acid. However, Saeves et al. did not confirm a significant correlation between tooth wear and obesity, sex, and consumption of acid beverages. In their opinion, PWS patients suffer from persistent hunger and a consequent urge to eat. When they are given access to soft drinks, it is therefore unlikely that drinking of the beverage is spread over time. This may go some way towards explaining the lack of association between high consumption of acid drinks and erosive wear [6]. Thirty-nine out of the 40 patients we examined were in the NHS Growth Hormone Program and followed a low-calorie diet. Seaves et al., however, observed that the intensity of tooth wear increased with age and it was associated with the reduced secretion of saliva [6]. According to our results, both salivary flow and salivary consistency seem to be important factors. Ramsay et al., likewise, confirmed a higher risk of significant tooth wear in subjects with reduced stimulated salivary flow and with thick, sticky, or frothy saliva [25]. These authors also showed that significance of these parameters was reduced when other risk factors of tooth wear were simultaneously taken into account.

It is known that impaired capability to dilute and neutralize acids increases acid effects on teeth, and consequently, the susceptibility to mechanical factors. Our results suggest that tooth wear may be favored by lower buffering ability of stimulated saliva and higher acidity of resting saliva. Nonetheless, significance of these parameters was not confirmed by a logistic regression analysis. Certainly, worse salivary quality and reduced amount of saliva both play important roles in the etiology of tooth wear [26]. Our observations are consistent with results of studies that confirm the effects of reduced salivary flow and its pH on the dental erosion rate [24, 26, 27]. However, a relationship with buffering capacity needs to be explained further due to contradictory reports. A relationship between lower buffering capacity and tooth wear [28, 29] and the lack of such a relationship [30‐32] were both demonstrated.

The relationship between teeth grinding and mouth breathing and lower secretion of saliva is also worth noticing. However, this relationship is not clearly demonstrated, as reduction of salivary flow is observed in subjects with bruxism [33]. It is also known that sleep-related reduction of salivary flow is a normal physiological process and rhythmic masticatory muscle activity (RMMA) during sleep may stimulate salivary secretion and may play an important role in lubricating the oral cavity. In subjects with sleep bruxism (SB), RMMA is more common and more intense compared to healthy subjects [34]. It is possible that in subjects with reduction of salivary flow, such as PWS patients, dried oroesophageal tissues promote the mechanism of saliva secretion via stimulation of the masticatory muscles during the night [35]. Mouth breathing is also associated with bruxism as it facilitates respiration [36, 37]. PWS patients are predisposed to sleep-disordered breathing due to a combination of characteristic craniofacial features, obesity, hypotonia, and hypothalamic dysfunction. In the post-infant period, more than 80% of PWS patients suffer from obstructive sleep apnea (OSA) [38].

Limited number of studies showed the predisposition to diseases of gingival and periodontal tissues in PWS. In the studies by Saeves et al., the median GI rates in the PWS group were 0.29 (0.06–0.65) and 0.17 (0.04–0.25) in the control group [5]. There were also reports of cases presenting periodontitis in a 20-year-old male patient [39] and a 13-year-old female patient [40]. Our PWS patients were susceptible to gingivitis but we did not see any clinical symptoms of periodontitis.

All authors highlighted the significance of both bad hygienic habits and mouth breathing in the etiology of gingivitis in these patients [5, 39, 40]. A tendency to chronic inflammation due to overactivation of the innate immune system in PWS might also be a contributing factor [41].

Our results confirm that the presence of the dental plaque is a significant factor causing gingivitis. However, changes in the salivary parameters are also important, as they contribute to more difficult teeth cleaning and they modify living conditions for bacteria. Reduction of salivary flow and saliva consistency other than watery favors accumulation of the dental plaque and gingivitis. In PWS group with mixed dentition, the mean value of GI was significantly higher than in the control group. At the same time, there was not a significant difference between mean values of PLI while the mean value of stimulated salivary flow was the highest of all groups. Interpretation of the results for the group with primary dentition is more difficult because of the lower gingival reaction to bacterial irritation in early childhood [42]. On the other hand, in permanent dentition groups, the influence of sex hormones should be taken into consideration. Hypogonadism is a constant feature in PWS and a cause of delayed or incomplete puberty of both males and females. Despite low testosterone levels in boys and low estradiol levels in girls with PWS, the mean value of GI was higher than in control group, though the difference was not statistically significant [1, 2, 43].

In case of gingivitis located in the anterior regions of the mandible and maxilla, mouth breathing also seems to be significant risk factor. It is known that chronic mouth breathing can cause localized gingivitis of the exposed gingiva in the maxillary and mandibular labial area. Gingival margins are rolled and interdental papillae are bulbous and enlarged. It indicates persisting inflammation in this area. Some authors also emphasize a relationship between mouth breathing and the GI value in children and it is consistent with our results [44]. On the other hand, in their studies with children between the age of 8 and 12 years, Piva et al. observed no correlation between gingivitis and mouth breathing [45].

There are various views on the relationship between gingivitis associated with mouth breathing and accumulation of the dental plaque [44, 46]. It was demonstrated, however, that stimulated saliva in patients who breathe through the mouth shows higher levels of free sialic acid, and it favors greater load of bacteria in the oral cavity [47]. Our studies confirmed that mouth breathing favors their presence on the teeth surfaces, but it has to be noted that a method applied to assess the hygiene status on index teeth was not completely reflected the effects of mouth breathing on the level of the dental plaque on labial surfaces of the anterior teeth. Nonetheless, salivary parameters, especially low salivary flow and increased viscosity of saliva, turned out to be important with regard to the etiology of gingivitis associated with mouth breathing.