Orthodontic treatment in children and adolescent patients with X-linked hypophosphatemia: A case-control study.

OBJECTIVES: X-linked hypophosphatemia (XLH) is a rare genetic disease that disturbs bone and teeth mineralization. It also affects craniofacial growth and patients with XLH often require orthodontic treatment. The aim of this study was to describe changes in the dental health of XLH children during orthodontic treatment compared with those in matched controls undergoing similar orthodontic procedures. MATERIALS AND METHODS: For this retrospective case-control study, we included all individuals less than 16 years old diagnosed with XLH, orthodontically treated in our centre from 2016 to 2022 and pair-matched them to patients with no chronic or genetic conditions. Clinical and radiological parameters concerning their malocclusion, craniofacial discrepancy and the characteristics and iatrogenic effects of their orthodontic treatment were analysed. RESULTS: Fifteen XLH patients (mean age: 11.3 ± 2.1), pair-matched to 15 control patients were included. Orthodontic treatment was successfully conducted in XLH patients with slightly shorter duration and similar iatrogenic effects as in the control group, except for the occurrence of dental abscess during and after orthodontic tooth movement. XLH patients did not show more relapse than the controls. CONCLUSION: Despite the presence of oral manifestations of XLH such as spontaneous abscesses, XLH patients can undergo orthodontic treatment with no obvious additional iatrogenic effects.

Dental and craniofacial features associated with GNAS loss of function mutations.

BACKGROUND: Pseudohypoparathyroidism (PHP, OMIM #103580) is a very rare disease (incidence 0.3-1/100,000). Heterozygous inactivating mutations involving the maternal GNAS exons 1-13 that encodes the alpha subunit of the stimulatory G protein (Gsα) cause inactivating parathyroid hormone (PTH)/PTHrP signalling disorder type 2 (iPPSD2 or PHP type 1A), which is characterized by Albright hereditary osteodystrophy and resistance to multiple hormones that act through the Gsα signalling pathway (including PTH, thyroid-stimulating hormone, and α-melanocyte-stimulating hormone). To date, little information is available on craniofacial features in patients with PHP. The small number of patients studied in previous reports as well as the lack of molecular characterization of the patients may have precluded the detection of specific orofacial manifestations in the different PHP subtypes. MATERIALS/METHODS: We conducted a systematic analysis of dental and craniofacial features in 19 patients with iPPSD2 and maternal GNAS inactivating mutations to assess the frequency and specificity of the anomalies. RESULTS: Facial examinations showed reduced vertical, sagittal, and transverse development of the mid-facial structures. Intraoral and radiographic examinations revealed that 89 per cent of the patients had at least one dental anomaly, including tooth submergence leading to severe infraocclusion in 83 per cent of cases. Craniofacial analysis of lateral cephalometric radiographs also showed a significant alteration in the development of the cranial base and maxillary and mandibular structures in these patients. CONCLUSIONS: Patients with iPPSD2 and maternal GNAS mutations had specific craniofacial alterations and dental abnormalities. These specific defects should be assessed in order to provide appropriate dental and orthodontic care to these patients. (clinical trial registration: 1920371 v 0, French Nationale Data Processing and Liberties Commission - CNIL).

Dental and periodontal manifestations of glycogen storage diseases: a case series of 60 patients.

Glycogen storage diseases (GSDs) are rare genetic disorders of glycogen metabolism where the liver, kidneys, respiratory and cardiac muscles, as well as the immune and skeletal systems can be affected. Oral manifestations can also be present, but the specificity and frequency of these manifestations in the different forms of GSD are unknown. Analysis of a case series of 60 patients presenting four types of GSD (Ia, Ib, III, and IX) showed that the different types of GSDs have common and specific oral manifestations. In none of the GSD types studied, the prevalence of caries was higher than in the general population, especially in patients benefiting from current nutritional therapy, while in all GSD types the prevalence of delayed tooth eruption, agenesis, and tooth shape abnormalities was increased compared to the general population. Severe periodontitis prevalence was increased in patients with GSD Ib and neutropenia. Our results show that GSDs have oral manifestations and suggest some specificity depending on the type of GSDs.

Risk Factors for High-Arched Palate and Posterior Crossbite at the Age of 5 in Children Born Very Preterm: EPIPAGE-2 Cohort Study.

Introduction: Children born very preterm have an immature sucking reflex at birth and are exposed to neonatal care that can impede proper palate growth. Objectives: We aimed to describe the frequency of high-arched palate and posterior crossbite at the age of 5 in children born very preterm and to identify their respective risk factors. Methods: Our study was based on the data from EPIPAGE-2, a French national prospective cohort study, and included 2,594 children born between 24- and 31-week gestation. Outcomes were high-arched palate and posterior crossbite. Multivariable models estimated by generalized estimation equations with multiple imputation were used to study the association between the potential risk factors studied and each outcome. Results: Overall, 8% of children born very preterm had a high-arched palate and 15% posterior crossbite. The odds of high-arched palate were increased for children with low gestational age (24-29 vs. 30-31 weeks of gestation) [adjusted odds ratio (aOR) 1.76, 95% confidence interval (CI) 1.17, 2.66], thumb-sucking habits at the age of 2 (aOR 1.53, 95% CI 1.03, 2.28), and cerebral palsy (aOR 2.18, 95% CI 1.28, 3.69). The odds of posterior crossbite were increased for children with pacifier-sucking habits at the age of 2 (aOR 1.75, 95% CI 1.30, 2.36). Conclusions: Among very preterm children, low gestational age and cerebral palsy are the specific risk factors for a high-arched palate. High-arched palate and posterior crossbite share non-nutritive sucking habits as a common risk factor. The oro-facial growth of these children should be monitored.

Effect of phosphorylation on the interaction of calcium with leucine-rich amelogenin peptide.

Amelogenin undergoes self-assembly and plays an essential role in guiding enamel mineral formation. The leucine-rich amelogenin peptide (LRAP) is an alternative splice product of the amelogenin gene and is composed of the N terminus (containing the only phosphate group) and the C terminus of full-length amelogenin. This study was conducted to investigate further the role of phosphorylation in LRAP self-assembly in the presence and absence of calcium using small angle X-ray scattering (SAXS). Consistent with our previous dynamic light-scattering findings for phosphorylated (+P) and non-phosphorylated (-P) LRAP, SAXS analyses revealed radii of gyration (R(g)) for LRAP(-P) (46.3-48.0 Å) that were larger than those for LRAP(+P) (25.0-27.4 Å) at pH 7.4. However, added calcium (up to 2.5 mM) induced significant increases in the R(g) of LRAP(+P) (up to 46.4 Å), while it had relatively little effect on LRAP(-P) particle size. Furthermore, SAXS analyses suggested compact folded structures for LRAP(-P) in the presence and absence of calcium, whereas the conformation of LRAP(+P) changed from an unfolded structure to a more compact structure upon the addition of calcium. We conclude that the single phosphate group in LRAP(+P) induces functionally important conformational changes, suggesting that phosphorylation may also influence amelogenin conformation and protein-mineral interactions during the early stages of amelogenesis.

Recommendations for Diagnosis and Treatment of Pseudohypoparathyroidism and Related Disorders: An Updated Practical Tool for Physicians and Patients.

Patients affected by pseudohypoparathyroidism (PHP) or related disorders are characterized by physical findings that may include brachydactyly, a short stature, a stocky build, early-onset obesity, ectopic ossifications, and neurodevelopmental deficits, as well as hormonal resistance most prominently to parathyroid hormone (PTH). In addition to these alterations, patients may develop other hormonal resistances, leading to overt or subclinical hypothyroidism, hypogonadism and growth hormone (GH) deficiency, impaired growth without measurable evidence for hormonal abnormalities, type 2 diabetes, and skeletal issues with potentially severe limitation of mobility. PHP and related disorders are primarily clinical diagnoses. Given the variability of the clinical, radiological, and biochemical presentation, establishment of the molecular diagnosis is of critical importance for patients. It facilitates management, including prevention of complications, screening and treatment of endocrine deficits, supportive measures, and appropriate genetic counselling. Based on the first international consensus statement for these disorders, this article provides an updated and ready-to-use tool to help physicians and patients outlining relevant interventions and their timing. A life-long coordinated and multidisciplinary approach is recommended, starting as far as possible in early infancy and continuing throughout adulthood with an appropriate and timely transition from pediatric to adult care.

Phosphorylated and Non-phosphorylated Leucine Rich Amelogenin Peptide Differentially Affect Ameloblast Mineralization.

The Leucine Rich Amelogenin Peptide (LRAP) is a product of alternative splicing of the amelogenin gene. As full length amelogenin, LRAP has been shown, in precipitation experiments, to regulate hydroxyapatite (HAP) crystal formation depending on its phosphorylation status. However, very few studies have questioned the impact of its phosphorylation status on enamel mineralization in biological models. Therefore, we have analyzed the effect of phosphorylated (+P) or non-phosphorylated (-P) LRAP on enamel formation in ameloblast-like cell lines and ex vivo cultures of murine postnatal day 1 molar germs. To this end, the mineral formed was analyzed by micro-computed tomography, Field Emission Scanning Electron Microscopy, Transmission Electron Microscopy, Selected Area Electon Diffraction imaging. Amelogenin gene transcription was evaluated by qPCR analysis. Our data show that, in both cells and germ cultures, LRAP is able to induce an up-regulation of amelogenin transcription independently of its phosphorylation status. Mineral formation is promoted by LRAP(+P) in all models, while LRAP(-P) essentially affects HAP crystal formation through an increase in crystal length and organization in ameloblast-like cells. Altogether, these data suggest a differential effect of LRAP depending on its phosphorylation status and on the ameloblast stage at the time of treatment. Therefore, LRAP isoforms can be envisioned as potential candidates for treatment of enamel lesions or defects and their action should be further evaluated in pathological models.

Diagnosis and management of pseudohypoparathyroidism and related disorders: first international Consensus Statement.

This Consensus Statement covers recommendations for the diagnosis and management of patients with pseudohypoparathyroidism (PHP) and related disorders, which comprise metabolic disorders characterized by physical findings that variably include short bones, short stature, a stocky build, early-onset obesity and ectopic ossifications, as well as endocrine defects that often include resistance to parathyroid hormone (PTH) and TSH. The presentation and severity of PHP and its related disorders vary between affected individuals with considerable clinical and molecular overlap between the different types. A specific diagnosis is often delayed owing to lack of recognition of the syndrome and associated features. The participants in this Consensus Statement agreed that the diagnosis of PHP should be based on major criteria, including resistance to PTH, ectopic ossifications, brachydactyly and early-onset obesity. The clinical and laboratory diagnosis should be confirmed by a molecular genetic analysis. Patients should be screened at diagnosis and during follow-up for specific features, such as PTH resistance, TSH resistance, growth hormone deficiency, hypogonadism, skeletal deformities, oral health, weight gain, glucose intolerance or type 2 diabetes mellitus, and hypertension, as well as subcutaneous and/or deeper ectopic ossifications and neurocognitive impairment. Overall, a coordinated and multidisciplinary approach from infancy through adulthood, including a transition programme, should help us to improve the care of patients affected by these disorders.

[Orthodontic and orthognathic protocoles: systematization of the consultation of announcement and contribution of integrative medicine]. / Protocole orthodontique et chirurgical : systématisation de la consultation d'annonce et apport de la médecine intégrative.

INTRODUCTION: The consultation of announcement is one of the key periods in an orthodontic and surgical process. The aim of this consultation is not only to make an aesthetic and orthodontic diagnosis but also a fine psychological analysis of the patient and his family before proposing a treatment plan. Integrative medical therapies, a recent evolution of medicine within the framework of the doctor-patient relation, have shown the positive impact on the treatment success of a good relationship. MATERIALS AND METHODS: The preliminary collection of information on the patient's psyches is now part of the treatment guidelines and has a positive impact on treatment observance, management of pre- and post-operative care or more simply surgery acceptance. Therefore, a systematized patient record process including global medical assessment of the patient and not only orthodontic and cephalometric diagnosis is a key factor for the treatment outcome.