Oral self-inflicted accidental trauma in patients with neurological disorders: a case report of dental management in infants with cerebellar hypoplasia.

Self-inflicted oral injuries, accidental or otherwise, can cause major consequences. Measures need to be taken to protect individuals from chronic self-injurious behaviour; however, there are no official guidelines on the subject. The purpose of this article is to show the case of a 1-year-old patient with neurological disorders who, following the eruption of deciduous teeth, had self-inflicted a traumatic ulcer on his tongue and lower lip. Following a multidisciplinary approach involving several operating units of our hospital to make a diagnosis, an oral device was designed to completely cover the dental elements to prevent recurrence of the trauma and to prevent further worsening of the injuries already caused. The purpose of this work is to demonstrate that although the surgical approach, such as extraction of the dental elements, may be the quickest solution in situations similar to the one presented, the high biological cost and irreversibility of the result lead to seeking alternatives and more conservative solutions such as the one described.

Cephalometric changes of pushing splints 3 compared to rapid maxillary expansion and facemask therapy on the airway space in class III growing patients: A randomized clinical trial.

BACKGROUND: Early orthopaedic treatment with rapid maxillary expansion (RME) associated with facemask (FM) has been shown to be effective in correcting Class III malocclusions in children. Treatment with pushing splints 3 (PS3) has shown to correct skeletal discrepancies in Class III growing patients. However, the effects of orthopaedic treatment on the upper airways in children with Class III malocclusion is controversial. OBJECTIVES: The aim of this study was to evaluate the cephalometric changes in the airways of PS3 compared to the RME/FM protocol. MATERIALS AND METHODS: In this study, 48 patients with Class III malocclusion (age range 5.5-8.5 years old) were selected for this study, and 24 were treated with PS3 appliance and 24 with RME/FM therapy. Lateral cephalograms before (T0) and at the end of the treatment (T1) were analysed to compare pharyngeal spaces. Paired and unpaired t tests were used for data analysis (P < .05). RESULTS: A total of 41 patients (21 patients for the PS3 group, 11 males and 10 females, mean age 7.0 ± 1.2 years; 20 patients for the RME/FM group, 10 males and 10 females, mean age 7.2 ± 1.3 years) were included. The results showed a statistically significant (P < .05) increase in the nasopharyngeal space after both therapies. However, the effects were similar considering that there were no differences between groups for the assessed variables at T0-T1. CONCLUSIONS: Early treatment of Class III malocclusion with PS3 does not induce a statistically significant increase in the sagittal airway space compared to RME/FM. The absence of untreated group could not define the role of growth in the increase of space.

Behavioral Modifications in Children after Repeated Sedation with Nitrous Oxide for Dental Treatment: A Retrospective Study.

Sedation with nitrous oxide (N2O) has been widely used as a viable alternative to general anesthesia to perform dental treatments in uncooperative or anxious children. The purpose of this retrospective study is to assess if repeated sedations with N2O can improve collaboration of uncooperative children. The medical records of 650 children, aged between 3 and 14 years, who underwent at least two sedations, were consulted. Differences in the Venham score during the first sedation and subsequent sedations were collected. After removal incomplete records, 577 children's records (309 males and 268 females) were analyzed. The Venham score decreased both during each sedation and with repeated sedations (p < 0.01 for both comparisons). In particular, a significant reduction of the Venham score was observed at the first contact with the dentist, with a mean score ranging from 1.56 ± 1.46 to 1.16 ± 1.37, comparing the first and the second sedation, and from 1.65 ± 1.43 to 1.06 ± 1.30, comparing the first with the third sedation (p < 0.01). The reduction in the Venham score was recorded in both healthy and physically impaired patients, and it was significantly greater in older children than in younger children (p < 0.01). In conclusion, uncooperative children with or without physical impairments can be successfully treated with N2O sedation in order to increase their confidence in dental procedures.

Effects of Rapid Palatal Expansion on the Upper Airway Space in Children with Obstructive Sleep Apnea (OSA): A Case-Control Study.

Obstructive Sleep Apnea (OSA) in children needs a multidisciplinary approach. Even if the first-line treatment of pediatric OSA is adenotonsillectomy, nowadays rapid palatal expansion (RPE) is considered a valid additional treatment. The aim of this study is to evaluate cephalometric changes in upper airways dimensions after rapid palatal expansion (RPE) in children suffering from Obstructive Sleep Apnea (OSA). A total of 37 children (range age 4-10 years) with diagnosis of OSA referred to Dentistry Unit of Bambino Gesù Children's Research Hospital IRCCS (Rome, Italy) were included in this pre-post study and underwent lateral radiographs at the start (T0) and at the end (T1) of a RPE treatment. Inclusion criteria were: diagnosis of OSA confirmed by cardiorespiratory polygraphy (AHI > 1) or pulse oximetry (McGill = >2), skeletal maxillary contraction evaluated by presence of posterior crossbite. A control group of 39 untreated patients (range age 4-11 years), in good general health, was set up. A paired T-test was used to investigate the statistical differences between T0 and T1 values in both groups. The results showed a statistically significant increase of nasopharyngeal width in the treated group after RPE treatment. Moreover, the angle that identifies mandibular divergence compared to palatal plane (PP-MP°) was significantly reduced. In the control group, no statistically significant differences were observed. The present study showed that RPE treatment determines a significant sagittal space increase in the upper airways space and a counterclockwise mandibular growth in children with OSA compared to a control group. These results suggest that a widening of the nasal cavities induced by RPE may support a return to physiological nasal breathing and promote a counterclockwise mandibular growth in children. This evidence confirms the crucial role of the orthodontist in the management of OSA in pediatric patients.

Diagnosis and Treatment of Nodular Fasciitis of Ear Region in Children: A Case Report and Review of Literature.

Nodular fasciitis (NF) is a benign fibroblastic and myofibroblastic proliferation of subcutaneous tissues. Rarely, it has been identified in the ear and more rarely in children. We describe a case in a four-year-old girl and the surgical management of it. The patient was referred to the otolaryngology unit of a tertiary referral center because she was affected by a painless and growing lesion in the left external auditory canal (EAC). The girl was treated by large-spectrum antibiotic therapy for one week without success. For this reason, we requested ultrasonography (US) of the left hemiface, maxillofacial and temporal bone computed tomography (CT) and magnetic resonance imaging (MRI) of the head with and without contrast. The imaging identified an irregular ovoid hypoechoic nodule with distinct margins indissociable from the cartilaginous planes and extending into the parotid loggia with local infiltration of the fascia. The lesion was surgically removed through preauricular access due its extension into the parotid area. The mass was excised in toto and sent to the pathologist for immunohistochemistry. The histopathologist based on the finding diagnosed a nodular fasciitis. In case of suspicion of malignancy, early investigations should be done to evaluate the lesion, then a traditional parotidectomy can be safely and successfully performed even in a very young child. The open technique allows the removal of NF with full control of the surgical area and facial nerve. In this article, we presented the management of a case in a 4-year-old female affected by NF of the external auditory canal (EAC), and we described clinical and surgical management of the case. We also reviewed literature of nodular fasciitis cases of ears in children.

"Multidisciplinary management of post- infective osteoarthritis and secondary condylar resorption of temporomandibular joint: a case report in a 9 years-old female patient and a review of literature".

BACKGROUND: Osteoarthritis and condylar resorption of temporomandibular joint (TMJ) has rarely been reported in children as consequence of otologic disease. We describe the management of a case in a 9-year-old female as long-term complication of an otomastoiditis and review the literature currently available on this topic. CASE PRESENTATION: A nine-years-old female patient referred to Emergency Room of Bambino Gesù Children's Research Hospital, IRCCS (Rome,Italy) for an acute pain in the left preauricular area and reduced mandibular movements. In the medical history an otomastoiditis and periorbital cellulitis was reported at the age of six with complete remission of symptoms after antibiotic treatment. No recent history of facial trauma and no previous orthodontic treatment were reported. She was referred to a pediatric dentist that conducted a clinical examination according to the Diagnostic Criteria of Temporomandibular Disorders (DC/TMD) and was diagnosed with bilateral myalgia of the masticatory muscles and arthralgia at the level of the left TMJ. Then, a complete diagnostic path was performed that included multidisciplinary examinations by a rheumatologist, infectious disease specialist, ear nose and throat (ENT) doctor, a maxillofacial surgeon and a medical imaging specialist. Differential diagnosis included juvenile idiopathic arthritis, idiopathic condylar resorption, trauma, degenerative joint disease, neurological disease. Finally, unilateral post-infective osteoarthritis of the left TMJ with resorption of mandibular condyle was diagnosed. The patient went through a pharmacological therapy with paracetamol associated to counselling, jaw exercises and occlusal bite plate. After 1 month, the patient showed significant reduction of orofacial pain and functional recovery that was confirmed also one-year post-treatment. The novelty of this clinical case lies in the accurate description of the multidisciplinary approach with clinical examination, the differential diagnosis process and the management of TMD with conservative treatment in a growing patient. CONCLUSIONS: Septic arthritis of temporomandibular joint and condylar resorption were described as complications of acute otitis media and/or otomastoiditis in children. We evidenced the importance of long-term follow-up in children with acute media otitis or otomastoiditis due to the onset of TMJ diseases. Furthermore, in the multidisciplinary management of orofacial pain the role of pediatric dentist is crucial for the diagnostic and therapeutic pathway to avoid serious impairment of mandibular function.

Conscious Sedation in Dentistry for the Management of Pediatric Patients with Autism: A Narrative Review of the Literature.

(1) Background: the variety of autism spectrum disorder makes the definition of guidelines for dental care a challenging task. The aim of this review was to evaluate the literature concerning the use of conscious sedation for dental treatments in pediatric autistic patients. (2) Methods: we searched MEDLINE/PubMed, EMBASE, Cochrane databases in order to identify pertinent studies. The search strategy was based on these areas of interest: autistic spectrum disorder, pediatric patients, dentistry, tranquilizing agents, and conscious sedation. (3) Results: the search yielded 177 non-duplicated articles, of which 24 articles were retrieved for full text review, and 2 were found to address our review aim. The first paper was a retrospective study that included 83 autistic patients sedated either with an oral premedication combined with nitrous oxide/oxygen inhalation or with nitrous oxide/oxygen inhalation alone; the second article was a prospective trial on the effectiveness of 0.3 mg/kg of oral diazepam with 0.5 mg/kg of oral midazolam in 13 sedated uncooperative autistic patients. (4) Conclusions: this review highlights the insufficiency of studies that can provide concrete indications for the dental treatment in conscious sedation of pediatric patients with autism. New studies are needed to better define the appropriate drugs, dosages, sedation level and evaluate patient cooperation.

Cross Sectional Study on the Association between Dental Caries and Life Habits in School Age Italian Children.

Dental caries is still a major public health issue and influences the overall health of children. The risk factors for caries include biological, socio-behavioral, and environmental factors. Our aim is to assess the association between dental caries and the life habits of children and their parents. A cross-sectional study was conducted in Rome (Italy) among primary school children aged 5 to 11. Parents completed the anamnestic questionnaire, and a dental clinical examination was performed on 333 children. Caries prevalence was 38.7% overall, 47% in males and 31.9% in females. The association between bottle night-time feeding and caries was statistically significant (43.2%; p = 0.013). Usage of a honeyed pacifier was also significantly associated with the presence of caries (72.7%; p = 0.027). Finally, higher caries prevalence was found among male children (47% vs. 31.9%; p = 0.005). The present study shows that the percentage of caries is still high in the paediatric population, and caries prevalence is associated with life habits. Our results highlight the importance of oral health education programs at primary school that involve teachers and parents to contribute to improving lifestyles.

Association between upper airway obstruction and malocclusion in mouth-breathing children.

OBJECTIVES: To evaluate the association between upper airway obstruction and occlusal anomalies in mouth-breathing children. METHODS: 356 mouth-breathing children were evaluated by ENT physicians and specialists in orthodontics. ENT examination included nasal endoscopy to assess the adenoidal hypertrophy, tonsillar grading and presence of nasal septum deviation. Clinical orthodontic examination was performed to record occlusal variables. Univariate and multivariable logistic regression were performed to study the association between registered variables. RESULTS: 221 patients (mean age ± sd = 6.2 ± 2.5 years) met inclusion criteria. 81.4% of children presented malocclusion. A significant association between tonsillar grade 2 and the presence of malocclusion, Class II relation and increased overjet was shown. Tonsillar grade 4 showed a significant association with the presence of malocclusion and increased overjet. Adenoidal hypertrophy and nasal septum deviation did not show any association with occlusal findings. CONCLUSIONS: A high frequency of orthodontic problems was seen in mouth-breathing children. Our results suggested that severe tonsillar hypertrophy may determine presence of malocclusion and increased overjet. On the other hand, the association between mild tonsillar hypertrophy and many occlusal anomalies in mouth-breathers suggest an important role of malocclusion in the onset of oral breathing in children.

Balloon dilation and rapid maxillary expansion: a novel combination treatment for congenital nasal pyriform aperture stenosis in an infant.

BACKGROUND: Congenital nasal pyriform aperture stenosis (CNPAS) is a rare condition that may occur alone or as part of a multi-formative syndrome. Management remains difficult. There is no specific treatment protocol. Traditional surgery would be anachronistic; a non-invasive or minimally invasive therapeutic option is required. However, the rarity of the disease and the infantile context render randomised clinical trials difficult. CASE PRESENTATION: We present the case of a one-month-old Caucasian boy with CNPAS. He presented to the Emergency Department of the Bambino Gesù Pediatric Hospital with nasal obstruction, noisy breathing, feeding difficulties, and suspected sleep apnoea. During hospitalisation, he underwent overnight pulse oximetry, airway endoscopy, and maxillofacial computed tomography (CT); the final diagnosis was CNPAS with moderate obstructive sleep apnoea syndrome. We successfully treated the patient using an innovative strategy that involved collaboration between ear-nose-and-throat surgeons and orthodontists. CONCLUSIONS: A combination of minimally invasive balloon surgery and placement of a palatal device may successfully treat CNPAS; it may also treat other types of nasal bone stenosis. Future studies may allow the development of practice consensus treatment strategies.

Dental and Periodontal Care at the Bedside Using a Portable Dental Unit in Hospitalized Special Needs Patients: The Experience of an Italian Pediatric Hospital.

Patients with special needs (SNPs) include individuals who are disabled due to physical limitations, medical complications, developmental problems, and cognitive impairments. SNPs may be at an increased risk of oral diseases throughout their lifetime. These patients have difficulties in accessing traditional dental studios or clinics. Moreover, orodental problems may cause local and generalized infections, leading to worrisome complications when not properly treated. In this paper, we describe the preliminary experience of treating dental problems in a series of nine hospitalized patients with special needs. This innovative protocol at the Bambino Gesù Children's Hospital (Rome, Italy) provides an introduction to a portable dental unit in order to perform oral care for hospitalized patients at the bedside. A multidisciplinary team composed of pediatric dentists, dental hygienists, nursing staff, and the patient's case manager was involved in the operative protocol. The SNPs described were affected by congenital heart or oncohematological diseases and neurodisabilities, and they were all hospitalized for different reasons: Open heart surgery, chemotherapy, organ transplantation, and rehabilitation. The oral evaluation was mandatory for ruling out or treating problems that could cause complications. Dental extractions, caries and fracture fillings, sealing, and oral hygiene procedures were performed at the bedside of the patients in the reference unit of their pediatric hospital. The results of this protocol confirm the feasibility of dental procedures at patients' bedside with portable dental units, encourage implementation of their use, and may represent an actionable model for oral care management in hospitalized SNPs.

Linguistic adaptation and psychometric evaluation of Italian version of children's sleep habits questionnaire.

BACKGROUND: The Children's Sleep Habits Questionnaire (CSHQ) is a parent-report questionnaire used to examine sleep behavior in children. Linguistic adaptation of CSHQ into several languages and/or psychometric analysis of reliability have been published. MAIN TEXT: Our aim was to translate the original 33-items CSHQ from English to Italian and to examine its reliability for use in 4-10 years-old children of Italy. After translation and back-translation procedure of the original CSHQ, the Italian CSHQ (CSHQ-IT) was administered to 69 mothers of healthy children. Reliability of CSHQ-IT was examined by the internal consistency of the scale (using the Cronbach's alpha coefficient), and by the test-retest analysis obtained by asking mothers who had completed the CSHQ-IT at baseline to re-complete it after a two-week interval (measured with the Lin's Concordance Correlation Coefficient, CCC). The CSHQ-IT showed adequate internal consistency (Cronbach's alpha = 0.81 for the total scale). The total CSHQ-IT score showed a strong correlation in retests (CCC 0.87; 95% Confidence Interval, 0.80; 0.92). CONCLUSION: CSHQ-IT is a valuable tool for evaluating sleep behavior in children 4-10 years-old in Italy. Future research should be implemented to provide definitive validity of CSHQ-IT in children with sleep-disordered breathing.

Cephalometric effects of Pushing Splints 3 compared with rapid maxillary expansion and facemask therapy in Class III malocclusion children: a randomized controlled trial.

BACKGROUND: Pushing Splints 3 (PS3) device was recently introduced for the treatment of Class III malocclusion in children. OBJECTIVES: To assess the effect on the sagittal maxillary position (SNA, primary outcome) of PS3 therapy compared with rapid maxillary expansion and facemask therapy (RME/FM) and to compare skeletal and dento-alveolar effects in growing Class III patients. TRIAL DESIGN: This trial was a single-centre randomized controlled trial with two groups randomly allocated in a 1:1 ratio of equal size by sealed-envelope randomization, conducted at the Dentistry Unit of Bambino Gesù Children's Hospital, IRCCS (Rome, Italy). METHODS: A total of 48 patients with Class III malocclusion were included in the study and randomly allocated to the two groups: PS3 therapy and RME/FM therapy. Only the RME/FM group underwent palatal expansion, and both groups were instructed to wear the appliances 14 hours/day. Pre- (T0) and post-treatment (T1) cephalograms were taken. An independent sample t-test and regression analysis were used to analyse the data (P value <0.05). Researchers involved in statistics and tracings were blinded to the treatment allocation. RESULTS: A total of 42 patients (21 for each group) completed the study. The maxillary sagittal position improved similarly in both groups (SNA = 0.4°; P = 0.547). A statistically significant decrease of SNPg angle (-1.6°; P < 0.001) and increase of ANPg angle (1.4°; P = 0.018) were found in the RME/FM group compared with PS3 group. CoGoMe angle significantly decreased in RME/FM group compared with PS3 group (-1.7°; P = 0.042). The regression analysis showed an association between SN/MP angle at T0 and the differences between T1 and T0 of SNPg (B = 0.13; P = 0.005) and SN/MP (B = -0.19; P = 0.034). Only three patients (PS3 = 2; RME/FM = 1) had breakages of the devices. LIMITATIONS: Results are limited to short-term effects. CONCLUSION: RME/FM therapy and PS3 are both effective therapies for the early correction of Class III malocclusion. The PS3 controlled better mandibular divergency reducing the clockwise rotation in patients with higher mandibular inclination. REGISTRATION: This study was not registered in a clinical trial registry.

Orofacial features and pediatric dentistry in the long-term management of Infantile Pompe Disease children.

BACKGROUND: Glycogen storage disease type II (GSDII) or Pompe disease is a rare autosomal recessive metabolic disorder that leads to intracellular glycogen storage in many tissues, mainly in skeletal muscle, heart and liver. Facial muscle weakness and altered craniofacial growth are very common in Pompe disease children. In this paper we describe the orofacial features in two children affected by GSDII and illustrate a multidisciplinary approach that involved enzyme replace therapy, non-invasive ventilation (NIV) and pediatric dentistry with 5-year follow-up. RESULTS: Two Infantile Pompe Disease children were examined by a pediatric dentist at the age of 4 and 5 years old respectively. The orofacial examination showed typical facies with similar features: hypotonia of facial and tongue muscles, lip incompetence, narrow palate with reduction in transversal dimension of the upper dental arch, macroglossia, low position of the tip of the tongue, concave profile, Class III malocclusion with hypoplasia of maxillary-malar area and mandibular prognathism. Myofunctional therapy and orthodontic treatment consisted in oral muscle exercises associated to intraoral and extraoral orthodontic devices. NIV facial mask was substituted with a nasal pillow mask in order to avoid external pressure on the mid-face which negatively influences craniofacial growth. CONCLUSIONS: This paper evidences that the pediatric dentist plays an important role in craniofacial growth control, oral function rehabilitation and, therefore, in the improvement of the quality of life of Pompe children and their families. Therefore an early pediatric dental evalutation should be included in the multidisciplinary management of children suffering from Infantile Pompe Disease.

Short-term effects of the Sander bite-jumping appliance on the pharyngeal airways in subjects with skeletal Class II malocclusion: A retrospective case-control study.

BACKGROUND: Skeletal Class II subjects present often a retruded mandible that might increase the probability of breathing disorders. OBJECTIVE: To evaluate the effects of functional treatment by means of the Sander bite-jumping appliance (BJA) on the upper airways of growing subjects. METHODS: Thirty-four subjects (21 males, 13 females; mean age 11.1 ± 1.2 years) with skeletal Class II malocclusion due to mandibular retrusion were treated with the Sander BJA (BJA group). The control group consisted of thirty-four untreated subjects with skeletal Class II malocclusion (25 males, 9 females; 10.4 ± 1.2 years; CTR group). The effect of the Sander BJA appliance on the airway dimensions was evaluated by comparing lateral cephalograms recorded before (T0) and after (T1) the period of observation/treatment. Within- and between-group comparisons were statistically evaluated according to the distribution of the data (P < .05). RESULTS: The oropharyngeal region (ph_pph) increased in the BJA group (1.8 ± 3.2; P = .001) but the difference respect to the CTR group was not statistically significant (0.73 ± 4.0; P = .314; P = .077). The tongue height (th) increased in the BJA group (2.8 ± 3.7; P < .001), and this increase was statistically significant respect to the CTR group (0.6 ± 4.7; P = .461; P = .038). In the BJA, the Ans_Pns_P angle showed a statistically significant decrease (-3.8 ± 7.8; P = .007) compared to the CTR group (-0.1 ± 5.4; P = .705; P = .026). CONCLUSIONS: The airway dimensions increased for both control subjects and Class II patients treated with Sander BJA due to physiological growth. The Sander BJA induced a statistically significant change in the tongue and soft palate position, but the clinically relevant of these changes is questionable.

MaNGA: a novel multi-niche multi-objective genetic algorithm for QSAR modelling.

SUMMARY: Quantitative structure-activity relationship (QSAR) modelling is currently used in multiple fields to relate structural properties of compounds to their biological activities. This technique is also used for drug design purposes with the aim of predicting parameters that determine drug behaviour. To this end, a sophisticated process, involving various analytical steps concatenated in series, is employed to identify and fine-tune the optimal set of predictors from a large dataset of molecular descriptors (MDs). The search of the optimal model requires to optimize multiple objectives at the same time, as the aim is to obtain the minimal set of features that maximizes the goodness of fit and the applicability domain (AD). Hence, a multi-objective optimization strategy, improving multiple parameters in parallel, can be applied. Here we propose a new multi-niche multi-objective genetic algorithm that simultaneously enables stable feature selection as well as obtaining robust and validated regression models with maximized AD. We benchmarked our method on two simulated datasets. Moreover, we analyzed an aquatic acute toxicity dataset and compared the performances of single- and multi-objective fitness functions on different regression models. Our results show that our multi-objective algorithm is a valid alternative to classical QSAR modelling strategy, for continuous response values, since it automatically finds the model with the best compromise between statistical robustness, predictive performance, widest AD, and the smallest number of MDs. AVAILABILITY AND IMPLEMENTATION: The python implementation of MaNGA is available at https://github.com/Greco-Lab/MaNGA. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Prevalence of malocclusion in children with obstructive sleep apnoea.

OBJECTIVES: To describe the prevalence of malocclusions in 2- to 10-year-old children suffering from obstructive sleep apnoea (OSA) and to evaluate the association between occlusal variables and OSA. SETTING AND SAMPLE POPULATION: A total of 2101 consecutive patients referred to an otorhinolaryngology unit were considered for the study. One hundred and fifty-six children (range 2-10 years) with suspected OSA were selected for a sleep study. The final sample consisted of 139 children suffering from OSA and a control group of 137 children. MATERIALS AND METHODS: All patients included in the study underwent a clinical orthodontic examination to record the following occlusal variables: primary canine relationship, presence of a posterior crossbite, overjet and overbite. Odds ratios and 95% confidence intervals, comparing the demographic characteristics and dental parameters in OSA vs non-OSA children, were computed. Multivariable logistic regression models were developed to compare independent variables associated with OSA to non-OSA children. RESULTS: The prevalence of malocclusions in children with OSA was 89.9% compared to 60.6% in the control group (P < 0.001). Factors independently associated with OSA compared to the control group were posterior crossbite (OR = 3.38; 95%CI:1.73-6.58), reduced overbite (OR = 2.43; 95%CI:1.15-5.15.), increased overbite (OR = 2.19; 95%CI:1.12-4.28) and increased overjet (OR = 4.25; 95%CI:1.90-9.48). CONCLUSIONS: This study showed a high prevalence of malocclusion in children with OSA compared to the control group. The posterior crossbite and deviations in overjet and overbite were significantly associated with OSA. The presence of these occlusal features shows the importance of an orthodontic evaluation in screening for paediatric OSA.

The Menkes and Wilson disease genes counteract in copper toxicosis in Labrador retrievers: a new canine model for copper-metabolism disorders.

The deleterious effects of a disrupted copper metabolism are illustrated by hereditary diseases caused by mutations in the genes coding for the copper transporters ATP7A and ATP7B. Menkes disease, involving ATP7A, is a fatal neurodegenerative disorder of copper deficiency. Mutations in ATP7B lead to Wilson disease, which is characterized by a predominantly hepatic copper accumulation. The low incidence and the phenotypic variability of human copper toxicosis hamper identification of causal genes or modifier genes involved in the disease pathogenesis. The Labrador retriever was recently characterized as a new canine model for copper toxicosis. Purebred dogs have reduced genetic variability, which facilitates identification of genes involved in complex heritable traits that might influence phenotype in both humans and dogs. We performed a genome-wide association study in 235 Labrador retrievers and identified two chromosome regions containing ATP7A and ATP7B that were associated with variation in hepatic copper levels. DNA sequence analysis identified missense mutations in each gene. The amino acid substitution ATP7B:p.Arg1453Gln was associated with copper accumulation, whereas the amino acid substitution ATP7A:p.Thr327Ile partly protected against copper accumulation. Confocal microscopy indicated that aberrant copper metabolism upon expression of the ATP7B variant occurred because of mis-localization of the protein in the endoplasmic reticulum. Dermal fibroblasts derived from ATP7A:p.Thr327Ile dogs showed copper accumulation and delayed excretion. We identified the Labrador retriever as the first natural, non-rodent model for ATP7B-associated copper toxicosis. Attenuation of copper accumulation by the ATP7A mutation sheds an interesting light on the interplay of copper transporters in body copper homeostasis and warrants a thorough investigation of ATP7A as a modifier gene in copper-metabolism disorders. The identification of two new functional variants in ATP7A and ATP7B contributes to the biological understanding of protein function, with relevance for future development of therapy.