RUNX2-related metaphyseal dysplasia with maxillary hypoplasia: A rare skeletal disorder resembling SFRP4-related Pyle disease.

Metaphyseal dysplasia with maxillary hypoplasia with or without brachydactyly (MDMHB) is an ultra-rare skeletal dysplasia caused by heterozygous intragenic RUNX2 duplications, comprising either exons 3 to 5 or exons 3 to 6 of RUNX2. In this study, we describe a 14-year-old Belgian boy with metaphyseal dysplasia with maxillary hypoplasia but without brachydactyly. Clinical and radiographic examination revealed mild facial dysmorphism, dental anomalies, enlarged clavicles, genua valga and metaphyseal flaring and thin cortices with an osteoporotic skeletal appearance. Exome sequencing led to the identification of a de novo heterozygous tandem duplication within RUNX2, encompassing exons 3 to 7. This duplication is larger than the ones previously reported in MDMHB cases since it extends into the C-terminal activation domain of RUNX2. We review previously reported cases with MDMHB and highlight the resemblance of this disorder with Pyle disease, which may be explained by intersecting molecular pathways between RUNX2 and sFRP4. This study expands our knowledge on the genotypic and phenotypic characteristics of MDMHB and the role of RUNX2 in rare bone disorders.

Evolution of root length throughout orthodontic treatment in maxillary incisors with previous history of dental trauma: a longitudinal controlled trial.

OBJECTIVES: To compare changes in root length of maxillary incisors with and without dental trauma throughout orthodontic treatment. MATERIALS AND METHOD: Patients younger than 18 years, with trauma on at least one maxillary incisor, undergoing orthodontic treatment between 2017 and 2021 were included, using the contralateral side as control without trauma when available. Periapical radiographs were taken pre-treatment and at 6 months intervals, and root/crown ratio was calculated. Linear mixed models were used to describe the evolution of root length at the different time points and to compare trauma and control values. Differences between central and lateral incisors and between treatment modalities were additionally explored. RESULTS: A total of 1768 measurements were performed on 499 teeth (201 with trauma) in 135 patients. Incisor root length significantly decreased during orthodontic treatment in teeth with and without trauma. Lateral incisors with trauma were more susceptible to root resorption than those without trauma and central incisors. No significant decrease in root length was observed with removable appliances, which never exceeded 15 months of treatment. Treatment with fixed appliances led to gradually increasing, significant root length shortening in teeth with and without trauma. CONCLUSION: Treatment duration directly correlated with root length shortening both in teeth with and without trauma history. Teeth with trauma showed significantly more root resorption after treatment with fixed appliances while removable appliances had no significant influence on root length. CLINICAL RELEVANCE: Previous history of dental trauma is no absolute contra-indication to start orthodontic treatment, as long as treatment duration is kept as short as possible.

Assessment of craniofacial maturation in preadolescents with cleft lip and/or palate using the cervical vertebral maturation method.

OBJECTIVES: Aberrant growth of the maxillomandibular complex in patients with cleft lip and/or palate (CL/P) can be managed with dentofacial orthopaedics. However, no consensus has been reached regarding timing and evolution of the maturational stages. Therefore, the aim of this study is to determine if patients with CL/P have an increased risk for delayed craniofacial maturation. MATERIALS AND METHODS: A sample of 246 cleft patients and 210 non-affected individuals was retrospectively compiled. Cephalometric radiographs taken between the ages of 10 and 14 years (girls) and 12 and 16 years (boys) were collected and assessed with the cervical vertebral maturation (CVM) method. RESULTS: In boys, no significant association between the presence of CL/P and a CVM score of CS3 or higher was observed in any age subsample. This was similar for a CVM score of CS5 or higher. Girls in the CL/P group had a significant lower probability of having a CVM score of at least CS3 in the subsample with age 11 to 12 (p = 0.001) and a borderline non-significant lower probability of having a CVM score of at least CS5 in the subsample with age 12 to 13 (p = 0.055). CONCLUSIONS: The current study demonstrated a discrete delay in skeletal maturation before the pubertal growth spurt of (pre)adolescents with CL/P, especially girls. This delay was less apparent at the end of the pubertal growth spurt. CLINICAL RELEVANCE: This research suggests that the craniofacial maturational stages relevant for dentofacial orthopaedic treatment in cleft patients, especially girls, occur at higher chronological age. Further research must quantify this delay, investigate its clinical significance, and determine its effect on the timing of dentofacial orthopaedic treatment.

A retrospective intercenter comparison of two surgical protocols through the dental arch relationship of 5- to 6-year-old unilateral cleft patients.

OBJECTIVES: The objectives of this retrospective equivalence trial were to assess the dental arch relationship of 5- to 6-year-old patients with unilateral cleft lip and palate (UCLP) treated in two specialized cleft centers with a different surgical protocol using the 5-Year-Olds' Index and the modified Huddart/Bodenham scoring system, and to determine the correlation between these two scoring indices. MATERIALS AND METHODS: The dental arch relationship of seventy-three 5- to 6-year-old patients with complete UCLP was evaluated on plaster casts using the 5-Year-Olds' Index and the modified Huddart/Bodenham scoring system. The sagittal occlusion, overbite, and overjet were also recorded. Inter- and intra-examiner agreement was determined using Intraclass Correlation Coefficients. RESULTS: A good to very good inter- and intra-examiner agreement was found. No significant mean difference in outcome based on the 5-Year-Olds' Index, the modified Huddart/Bodenham scoring system, overjet, or overbite was detected. For mean difference in sagittal occlusion, the hypothesis that both centers are clinically equivalent was confirmed. A strong negative correlation (rs = - 0.832) between the 5-Year-Olds' Index and the modified Huddart/Bodenham scoring system was found. CONCLUSIONS: The dental arch relationship of 5- to 6-year-old unilateral cleft patients treated in two Belgian cleft centers is clinically equivalent based on sagittal occlusion, despite substantial differences in their treatment protocol. Clinical equivalence for other parameters was not confirmed. There is a strong correlation between the 5-Year-Olds' Index and the modified Huddart/Bodenham scoring system. CLINICAL RELEVANCE: A well-implemented treatment protocol for cleft patients is of the utmost importance, but case load and skill of the surgeon are also important factors for the quality of the results.

Pediatric cleft palate patients show a 3- to 5-fold increase in cumulative radiation exposure from dental radiology compared with an age- and gender-matched population: a retrospective cohort study.

OBJECTIVE: The objective of the study was to compare estimates of pediatric cumulative exposure and lifetime attributable risk (LAR) of radiation-induced cancer from dental radiology between cleft palate (CP) subjects and age- and gender-matched controls (non-CP), with and without orthodontic treatment. MATERIALS AND METHODS: The radiation exposure frequency of CP subjects and non-CP controls with and without orthodontic treatment was compared for two-dimensional radiography (intra-oral, panoramic and cephalometric radiography), computed tomography (CT), and cone-beam CT (CBCT) using cumulative radiation dose as an estimate. From this dose estimate, the age- and gender-dependent risk for radiation-induced stochastic effects was calculated for each patient group. RESULTS: CP patients received more radiographic examinations than non-CP controls, with the exception of intra-oral radiographs. The cumulative dose to CP patients was considerably higher (1963 µSv at the age of 20 years) than non-CP patients with (597 µSv) and without (383 µSv) orthodontic treatment, primarily due to the higher frequency of CT scanning. Accordingly, CP patients had a three to five times higher LAR than non-CP patients. CONCLUSIONS: This study suggests a significantly higher lifetime radiation exposure to CP patients than non-CP controls from dental radiographic procedures. Diagnostic benefits from the use of CT and CBCT in children must be justified and appropriate dose optimization strategies implemented. CLINICAL RELEVANCE: The present study indicates the need for proper justification and optimization of pediatric exposures in dentistry, with a special focus on high-risk groups.

AGORA, a data- and biobank for birth defects and childhood cancer.

BACKGROUND: Research regarding the etiology of birth defects and childhood cancer is essential to develop preventive measures, but often requires large study populations. Therefore, we established the AGORA data- and biobank in the Netherlands. In this study, we describe its rationale, design, and ongoing data collection. METHODS: Children diagnosed with and/or treated for a structural birth defect or childhood cancer and their parents are invited to participate in the AGORA data- and biobank. Controls are recruited through random sampling from municipal registries. The parents receive questionnaires about demographics, family and pregnancy history, health status, prescribed medication, lifestyle, and occupational exposures before and during the index pregnancy. In addition, blood or saliva is collected from children and parents, while medical records are reviewed for diagnostic information. RESULTS: So far, we have collected data from over 6,860 families (3,747 birth defects, 905 childhood cancers, and 2,208 controls). The types of birth defects vary widely and comprise malformations of the digestive, respiratory, and urogenital tracts as well as facial, cardiovascular, kidney, skeletal, and central nervous system anomalies. The most frequently occurring childhood cancer types are acute lymphatic leukemia, Hodgkin and non-Hodgkin lymphoma, Wilms' tumor, and brain and spinal cord tumors. Our genetic and/or epidemiologic studies have been focused on hypospadias, anorectal malformations, congenital anomalies of the kidney and urinary tract (CAKUT), and orofacial clefts. CONCLUSION: The large AGORA data- and biobank offers great opportunities for investigating genetic and nongenetic risk factors for disorders in children and is open to collaborative initiatives. Birth Defects Research (Part A) 106:675-684, 2016. © 2016 Wiley Periodicals, Inc.

Novel mutations in LRP6 highlight the role of WNT signaling in tooth agenesis.

PURPOSE: We aimed to identify a novel genetic cause of tooth agenesis (TA) and/or orofacial clefting (OFC) by combining whole-exome sequencing (WES) and targeted resequencing in a large cohort of TA and OFC patients. METHODS: WES was performed in two unrelated patients: one with severe TA and OFC and another with severe TA only. After deleterious mutations were identified in a gene encoding low-density lipoprotein receptor-related protein 6 (LRP6), all its exons were resequenced with molecular inversion probes in 67 patients with TA, 1,072 patients with OFC, and 706 controls. RESULTS: We identified a frameshift (c.4594delG, p.Cys1532fs) and a canonical splice-site mutation (c.3398-2A>C, p.?) in LRP6, respectively, in the patient with TA and OFC and in the patient with severe TA only. The targeted resequencing showed significant enrichment of unique LRP6 variants in TA patients but not in nonsyndromic OFC patients. Of the five variants in patients with TA, two affected the canonical splice site and three were missense variants; all variants segregated with the dominant phenotype, and in one case the missense mutation occurred de novo. CONCLUSION: Mutations in LRP6 cause TA in humans.Genet Med 18 11, 1158-1162.

Clinical problems with a double tooth and a macrodont in the maxillary anterior area: a case report.

BACKGROUND: Fusion is defined as the union between dentine and/or enamel of two normally separated teeth. Gemination is the cleavage of the forming dental germ to produce two partial teeth. The distinction between the conditions is often determined by the number of teeth present. However, this can be confused if supernumerary teeth are considered. AIM: The present case report describes the treatment of a patient who presented with dental fusion and macrodontia involving both upper central incisors. Besides the central incisors displaying characteristics of macrodonts, tooth 21 also showed aspects of fusion. METHODS: Management consisted of the extraction of 11 and 21 and orthodontic mesialisation of the maxillary dentition. Treatment was planned in two phases and at the end of the orthodontic phase, the upper anterior teeth were to be reshaped using composite resin. RESULTS: Orthodontic space closure is a treatment option in the clinical management of an extracted maxillary central double and/or macrodontic tooth. As no permanent teeth were absent, it was presumed that the fusion of 21 occurred with a supernumerary tooth. CONCLUSIONS: Multidisciplinary treatment following the extraction of maxillary central incisors is reported with special attention to the orthodontic and restorative considerations required to improve the aesthetic outcome.

Variation in dentofacial morphology and occlusion in juvenile idiopathic arthritis subjects: a case-control study.

Juvenile idiopathic arthritis (JIA) can severely disturb facial growth and affect occlusal development. In this case-control study, facial, functional, and occlusal characteristics of 100 JIA patients (35 males and 65 females; age range: 1.7-19.4 years) comprising all subtypes classified according to the revised classification criteria of the International League of Associations for Rheumatology (ILAR) were studied. They were compared with a mixed orthodontic control group (n=32; 12 males and 20 females) and with a Class II division 1 malocclusion group (n=19; eight males and 11 females). The JIA patients and controls were evaluated using clinical assessment, dental pantomograms, lateral cephalograms (LCGs), and dental casts. Compared with the age- and gender-matched mixed orthodontic controls, JIA patients showed a significantly greater prevalence of anterior open bites (AOBs; P<0.05; Wilcoxon matched pairs test). Cephalometrically, a larger mandibular plane (P<0.05) and SNA (P<0.001) angles and a smaller interincisal angle (P<0.001) were found. In comparison with the Class II division 1 controls, JIA patients showed a larger SNA (P<0.001; Wilcoxon matched pairs test) and SNB (P<0.05) angles and smaller lower anterior face heights (LAFHs; P<0.05). No differences were found for the mandibular plane, the gonial and the interincisal angles, or total face height. From this case-control study, it can be concluded that although JIA patients share occlusal characteristics with non-JIA patients with a Class II division 1 malocclusion, they are different with regard to the prevalence of condylar lesions and AOBs, as well as SNA and SNB angles and LAFH.

Temporomandibular joint arthritis in juvenile idiopathic arthritis: prevalence, clinical and radiological signs, and relation to dentofacial morphology.

OBJECTIVE: To perform a prospective, comprehensive, clinical, and radiological evaluation of temporomandibular joint (TMJ) involvement and its influence on craniofacial growth, in a cohort of patients with juvenile idiopathic arthritis (JIA), representing all JIA subtypes. METHODS: Clinical rheumatologic and orthodontic evaluations were performed in 100 patients with JIA [12 systemic arthritis, 24 rheumatoid factor (RF)-negative polyarthritis, 1 RF-positive polyarthritis, 39 oligoarthritis, 22 enthesitis-related arthritis, 2 psoriatic arthritis]. An orthopantomogram and lateral cephalogram were performed in 46 patients. The prevalence of TMJ arthritis was studied in relation to JIA subtype and disease characteristics; cephalometric measurements were compared to those from age- and sex-matched healthy controls. RESULTS: Whereas 55% of patients with JIA had at least one symptom/sign of TMJ arthritis, 78% of the radiographed group exhibited condylar lesions. The presence of condylar damage was not related to clinical orthodontic findings or to JIA subtype, disease activity, severity, or duration. Patients with JIA exhibited larger mandibular plane and A-nasion-B angles, larger total anterior facial height, smaller interincisal and sella-nasion-B angles, and shorter mandibular ramus lengths than their age- and sex-matched controls. Craniofacial alterations were clearly related to the presence of condylar damage, even when present at a minimal degree. CONCLUSION: Our data show that TMJ condylar damage occurs very frequently in JIA, and irrespective of JIA subtype; condylar lesions can present early, progress insidiously, and -- even at a minimal degree -- can severely alter the craniofacial profile. We propose that the followup of patients with JIA should include early and regular evaluation by an orthodontist, supplemented with radiographic TMJ imaging.