New microdeletion and microduplication syndromes: A comprehensive review.

Several new microdeletion and microduplication syndromes are emerging as disorders that have been proven to cause multisystem pathologies frequently associated with intellectual disability (ID), multiple congenital anomalies (MCA), autistic spectrum disorders (ASD) and other phenotypic findings. In this paper, we review the "new" and emergent microdeletion and microduplication syndromes that have been described and recognized in recent years with the aim of summarizing their main characteristics and chromosomal regions involved. We decided to group them by genomic region and within these groupings have classified them into those that include ID, MCA, ASD or other findings. This review does not intend to be exhaustive but is rather a quick guide to help pediatricians, clinical geneticists, cytogeneticists and/or molecular geneticists.

Effects of orthodontic treatment with aligners and fixed appliances on speech.

OBJECTIVES: To evaluate effects of orthodontic treatment with aligners and conventional fixed appliances on production of speech. MATERIALS AND METHODS: This was a parallel, randomized clinical trial. Patients with Angle Class I malocclusion, moderate crowding, and no speech impairment were randomly allocated to two groups: patients with orthodontic aligners (OAs; n = 20; mean age = 23.60 ± 5.65 years) and those with conventional fixed appliances (n = 20; mean age = 20.56 ± 4.51 years) and treated at the University of North Parana's clinic in Londrina, Brazil. Evaluation of speech production was performed semiobjectively by a speech therapist (myofunctional orofacial examination) and subjectively (self-assessment) at five time points: baseline, immediately after insertion of appliances, and subsequently at 3, 30, and 180 days after insertion. For intergroup comparison, independent t, χ2, Fisher exact, and Mann-Whitney tests were used; for intragroup comparison, the Friedman test was applied (α = 5%). RESULTS: In the semiobjective evaluation, patients with OAs exhibited a change in production of speech production, compared with patients with fixed appliances, immediately and 3 days after insertion of appliances (P < .001). Thirty days after insertion, the groups were similar (P = .487), an outcome that was unchanged at 180 days. However, in the self-assessments, patients in both groups reported significant speech difficulties immediately and 3 days after insertion of appliances, but such impairment was no longer perceived at 30 days or 180 days. CONCLUSIONS: Although the speech therapist identified changes in speech production at the start of treatment in the OA group only, patient self-assessments demonstrated that orthodontic treatment, regardless of the type of appliance used, interfered with their perception of speech.

Cytogenomic Evaluation of Subjects with Syndromic and Nonsyndromic Conotruncal Heart Defects.

Despite considerable advances in the detection of genomic abnormalities in congenital heart disease (CHD), the etiology of CHD remains largely unknown. CHD is the most common birth defect and is a major cause of infant morbidity and mortality, and conotruncal defects constitute 20% of all CHD cases. We used array comparative genomic hybridization (array-CGH) to retrospectively study 60 subjects with conotruncal defects and identify genomic imbalances. The DNA copy number variations (CNVs) detected were matched with data from genomic databases, and their clinical significance was evaluated. We found that 38.3% (23/60) of CHD cases possessed genomic imbalances. In 8.3% (5/60) of these cases, the imbalances were causal or potentially causal CNVs; in 8.3% (5/60), unclassified CNVs were identified; and in 21.6% (13/60), common variants were detected. Although the interpretation of the results must be refined and there is not yet a consensus regarding the types of CHD cases in which array-CGH should be used as a first-line test, the identification of these CNVs can assist in the evaluation and management of CHD. The results of such studies emphasize the growing importance of the use of genome-wide assays in subjects with CHD to increase the number of genomic data sets associated with this condition.

Reliability of a method to conduct upper airway analysis in cone-beam computed tomography.

The aim of this study was to assess the reliability of a method to measure the following upper airway dimensions: total volume (TV), the nasopharyngeal narrowest areas (NNA), and the oropharyngeal narrowest areas (ONA). The sample consisted of 60 cone-beam computed tomography (CBCT) scans, evaluated by two observers twice, using the Dolphin 3D software (Dolphin Imaging & Management solutions, Chatsworth, California, USA), which afforded image reconstruction, and measurement of the aforementioned dimensions. The data was submitted to reliability tests, by the intraclass correlation coefficient (ICC), and the Bland & Altman agreement tests, with their respective confidence intervals (CI) set at 95%. Excellent intra- and interobserver reliability values were found for all variables assessed (TV, NNA and ONA), with ICC values ranging from 0.88 to 0.99. The data demonstrated an agreement between the two assessments of each observer and between the first evaluations of both observers, thus confirming the reliability of this methodology. The results suggest that this methodology can be used in further studies to investigate upper airway dimensions (TV, NNA, and ONA), thereby contributing to the diagnosis of upper airway obstructions.

Serial extraction: 20 years of follow-up.

This paper reports a case treated by a serial extraction program at the mixed dentition stage followed by a corrective orthodontic treatment, with a long-term follow-up period. Twenty years after the interceptive treatment, a harmonious face was observed along with treatment stability in the anterior posterior direction, deep overbite (which has been mentioned as a disadvantage of the serial extraction program), and a small relapse of anterior tooth crowding. All these conditions have been regarded as normal occurrences for most orthodontic treatments with a long-term follow-up period. This case report demonstrated that the establishment of a serial extraction protocol determined relevant esthetic changes that afforded an improvement of the patient's self-esteem, with a positive social impact. Furthermore, the low cost of this protocol permits the use of this therapy with underprivileged populations. It is important to emphasize that an early correction of tooth crowding by this protocol does not guarantee stability, but small relapses do not invalidate its accomplishment.

Molecular cytogenetic evaluation of chromosomal microdeletions: the experience of a public hospital in Southern Brazil

Introduction: During the past few decades, the number of diseases identified to be caused by chromosomal microdeletions has increased quickly, bringing a new and crucial role for cytogenetics on the diagnosis of these conditions. The purpose of this study was to identify and characterize chromosomal microdeletions associated with malformation syndromes and intellectual disability. Methods: We retrospectively evaluated a consecutive series of samples from a cohort of 598 subjects with clinical symptoms of a microdeletion syndrome, including the deletion of chromosomes 4p16.3, 5p15.2, 5q35, 7q11.23, 8q24.12, 15q11.2, 16p13.3, 17p13.3, 17p11.2,2, and 22q11.2, as investigated by fluorescence in situ hybridization (FISH). Array-based comparative genomic hybridization (array-CGH) was performed on 25 samples with microdeletions. Results: A total of 598 samples were evaluated from patients whose clinical phenotypes were most indicative of 22q11.2 deletion syndrome (29.10%), Prader-Willi syndrome (23.41%), Angelman syndrome (16.89%), and Williams-Beuren syndrome (14.72%). In 142 of the samples (23.75%), a chromosomal imbalance associated with phenotypic abnormalities was found. The deletion of 7q11.23 was the most frequent (8.03%), followed by del22q11.2 (5.68%) and del15q11.2 (5%). Conclusion: Our study reinforces the idea that the effort to improve the capacity to perform molecular cytogenetic investigations associated with a qualified clinical evaluation is crucial for the detection and precise characterization of submicroscopic chromosome deletions, bringing benefits to patients, relatives, and genetic counselors. It also contributes to the continuing education of cytogeneticists and to the knowledge of chromosomal rearrangements associated with genomic disorders.

Reliability of a method to conduct upper airway analysis in cone-beam computed tomography

The aim of this study was to assess the reliability of a method to measure the following upper airway dimensions: total volume (TV), the nasopharyngeal narrowest areas (NNA), and the oropharyngeal narrowest areas (ONA). The sample consisted of 60 cone-beam computed tomography (CBCT) scans, evaluated by two observers twice, using the Dolphin 3D software (Dolphin Imaging & Management solutions, Chatsworth, California, USA), which afforded image reconstruction, and measurement of the aforementioned dimensions. The data was submitted to reliability tests, by the intraclass correlation coefficient (ICC), and the Bland & Altman agreement tests, with their respective confidence intervals (CI) set at 95%. Excellent intra- and interobserver reliability values were found for all variables assessed (TV, NNA and ONA), with ICC values ranging from 0.88 to 0.99. The data demonstrated an agreement between the two assessments of each observer and between the first evaluations of both observers, thus confirming the reliability of this methodology. The results suggest that this methodology can be used in further studies to investigate upper airway dimensions (TV, NNA, and ONA), thereby contributing to the diagnosis of upper airway obstructions.

Serial extraction: 20 years of follow-up

This paper reports a case treated by a serial extraction program at the mixed dentition stage followed by a corrective orthodontic treatment, with a long-term follow-up period. Twenty years after the interceptive treatment, a harmonious face was observed along with treatment stability in the anterior posterior direction, deep overbite (which has been mentioned as a disadvantage of the serial extraction program), and a small relapse of anterior tooth crowding. All these conditions have been regarded as normal occurrences for most orthodontic treatments with a long-term follow-up period. This case report demonstrated that the establishment of a serial extraction protocol determined relevant esthetic changes that afforded an improvement of the patient's self-esteem, with a positive social impact. Furthermore, the low cost of this protocol permits the use of this therapy with underprivileged populations. It is important to emphasize that an early correction of tooth crowding by this protocol does not guarantee stability, but small relapses do not invalidate its accomplishment.