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Journal of the World Federation of... Aug 2023Maxillary transverse deficiency can occur in various clinical dentoskeletal deformities and include unilateral or bilateral posterior crossbite, narrow, tapering, or... (Review)
Review
Maxillary transverse deficiency can occur in various clinical dentoskeletal deformities and include unilateral or bilateral posterior crossbite, narrow, tapering, or high palatal arch. The development of temporary anchorage devices led to a new generation of tooth-bone-borne expansion appliance using two or four screws to apply the mechanical forces to the bone and reduce the stress to the anchored teeth. The aim of these new devices is to reduce the adverse dentoalveolar effect and achieve more skeletal expansion than conventional tooth-borne rapid palatal expansion. This article reviews the age limitation and complication and soft tissue change of nonsurgical maxillary expansion. We discuss the approach of surgical maxillary expansion with maxillary skeletal expander device. The clinical case will show the benefit of nonsurgical and surgical tooth-bone-borne rapid palatal expansion.
Topics: Humans; Palatal Expansion Technique; Orthodontic Appliance Design; Maxilla; Palate; Malocclusion; Micrognathism
PubMed: 37344295
DOI: 10.1016/j.ejwf.2023.04.005 -
Genes Jun 2021Coffin-Siris syndrome (CSS, MIM 135900) is a multi-system intellectual disability syndrome characterized by classic dysmorphic features, developmental delays, and organ...
Coffin-Siris syndrome (CSS, MIM 135900) is a multi-system intellectual disability syndrome characterized by classic dysmorphic features, developmental delays, and organ system anomalies. Genes in the BRG1(BRM)-associated factors (BAF, Brahma associated factor) complex have been shown to be causative, including , , , , , , , , , and . In order to describe more robust genotype-phenotype correlations, we collected data from 208 individuals from the CSS/BAF complex registry with pathogenic variants in seven of these genes. Data were organized into cohorts by affected gene, comparing genotype groups across a number of binary and quantitative phenotypes. We determined that, while numerous phenotypes are seen in individuals with variants in the BAF complex, hypotonia, hypertrichosis, sparse scalp hair, and hypoplasia of the distal phalanx are still some of the most common features. It has been previously proposed that individuals with -related variants are thought to have more learning and developmental struggles, and individuals with -related variants, while they also have developmental delay, tend to have more severe organ-related complications. -related variants also have developmental differences and organ-related complications but are most associated with neurodevelopmental differences. While these generalizations still overall hold true, we have found that all individuals with BAF-related conditions are at risk of many aspects of the phenotype, and management and surveillance should be broad.
Topics: Abnormalities, Multiple; Face; Genotype; Hand Deformities, Congenital; Humans; Intellectual Disability; Micrognathism; Mutation; Neck; Phenotype; Transcription Factors
PubMed: 34205270
DOI: 10.3390/genes12060937 -
American Journal of Obstetrics and... Nov 2019
Topics: Delivery, Obstetric; Diagnosis, Differential; Female; Fetus; Genetic Testing; Humans; Micrognathism; Pregnancy; Prognosis; Ultrasonography, Prenatal
PubMed: 31679587
DOI: 10.1016/j.ajog.2019.08.051 -
Clinics in Plastic Surgery Jul 2021A combined surgical and orthodontic approach to midface and mandibular distraction optimizes stability and outcomes. Orthodontic considerations include proper planning... (Review)
Review
A combined surgical and orthodontic approach to midface and mandibular distraction optimizes stability and outcomes. Orthodontic considerations include proper planning of the distraction vector, appropriate device use, and thorough follow-up through the consolidation and postoperative period. The dental occlusion must be managed throughout treatment in order to achieve ideal results.
Topics: Humans; Male; Mandible; Maxilla; Micrognathism; Orthognathic Surgical Procedures; Osteogenesis, Distraction
PubMed: 34051904
DOI: 10.1016/j.cps.2021.02.009 -
Genetics in Medicine : Official Journal... Nov 2023Coffin-Siris and Nicolaides-Baraitser syndromes are recognizable neurodevelopmental disorders caused by germline variants in BAF complex subunits. The SMARCC2 BAFopathy...
PURPOSE
Coffin-Siris and Nicolaides-Baraitser syndromes are recognizable neurodevelopmental disorders caused by germline variants in BAF complex subunits. The SMARCC2 BAFopathy was recently reported. Herein, we present clinical and molecular data on a large cohort.
METHODS
Clinical symptoms for 41 novel and 24 previously published affected individuals were analyzed using the Human Phenotype Ontology. For genotype-phenotype correlations, molecular data were standardized and grouped into non-truncating and likely gene-disrupting (LGD) variants. Missense variant protein expression and BAF-subunit interactions were examined using 3D protein modeling, co-immunoprecipitation, and proximity-ligation assays.
RESULTS
Neurodevelopmental delay with intellectual disability, muscular hypotonia, and behavioral disorders were the major manifestations. Clinical hallmarks of BAFopathies were rare. Clinical presentation differed significantly, with LGD variants being predominantly inherited and associated with mildly reduced or normal cognitive development, whereas non-truncating variants were mostly de novo and presented with severe developmental delay. These distinct manifestations and non-truncating variant clustering in functional domains suggest different pathomechanisms. In vitro testing showed decreased protein expression for N-terminal missense variants similar to LGD.
CONCLUSION
This study improved SMARCC2 variant classification and identified discernible SMARCC2-associated phenotypes for LGD and non-truncating variants, which were distinct from other BAFopathies. The pathomechanism of most non-truncating variants has yet to be investigated.
Topics: Humans; Abnormalities, Multiple; Face; Micrognathism; Intellectual Disability; Facies; Neurodevelopmental Disorders; Phenotype; DNA-Binding Proteins; Transcription Factors
PubMed: 37551667
DOI: 10.1016/j.gim.2023.100950 -
Neurological Sciences : Official... Feb 2021Coffin-Siris syndrome is a rare genetic disorder defined by the presence of particular facial traits, congenital malformations, intellectual disability, and speech...
Coffin-Siris syndrome is a rare genetic disorder defined by the presence of particular facial traits, congenital malformations, intellectual disability, and speech impairment. Epilepsy in Coffin-Siris syndrome has only occasionally been reported, and its features are poorly defined. We provide a detailed description of the clinical and instrumental findings of three patients with Coffin-Siris syndrome and epilepsy. The clinical diagnosis in our patients was confirmed by molecular analysis, which identified the presence of de novo mutations of ARID1B and SMARCB1 genes, in two patients and one patient, respectively. All the patients presented with epilepsy, with a mean age of seizure onset of 5.5 years. Seizures were brief and had a focal onset with secondary generalization. Electroencephalographic recording documented a unilateral, and less commonly bilateral, paroxysmal activity in the temporal, parietal, and occipital regions. Clinical response to anticonvulsive therapy was satisfactory, with a low rate of seizure recurrence. Our case series contributes to delineate the phenotype of Coffin-Siris syndrome. We wish this report could pave the way for further studies that will better define the prevalence and clinical manifestations of epilepsy in this rare syndrome.
Topics: Abnormalities, Multiple; Child, Preschool; Chromosomal Proteins, Non-Histone; DNA-Binding Proteins; Epilepsy; Face; Hand Deformities, Congenital; Humans; Intellectual Disability; Micrognathism; Neck
PubMed: 33006724
DOI: 10.1007/s10072-020-04782-y -
Nucleic Acids Research Oct 2023Faithful cell division is the basis for the propagation of life and DNA replication must be precisely regulated. DNA replication stress is a prominent endogenous source...
Faithful cell division is the basis for the propagation of life and DNA replication must be precisely regulated. DNA replication stress is a prominent endogenous source of genome instability that not only leads to ageing, but also neuropathology and cancer development in humans. Specifically, the issues of how vertebrate cells select and activate origins of replication are of importance as, for example, insufficient origin firing leads to genomic instability and mutations in replication initiation factors lead to the rare human disease Meier-Gorlin syndrome. The mechanism of origin activation has been well characterised and reconstituted in yeast, however, an equal understanding of this process in higher eukaryotes is lacking. The firing of replication origins is driven by S-phase kinases (CDKs and DDK) and results in the activation of the replicative helicase and generation of two bi-directional replication forks. Our data, generated from cell-free Xenopus laevis egg extracts, show that DONSON is required for assembly of the active replicative helicase (CMG complex) at origins during replication initiation. DONSON has previously been shown to be essential during DNA replication, both in human cells and in Drosophila, but the mechanism of DONSON's action was unknown. Here we show that DONSON's presence is essential for replication initiation as it is required for Cdc45 and GINS association with Mcm2-7 complexes and helicase activation. To fulfil this role, DONSON interacts with the initiation factor, TopBP1, in a CDK-dependent manner. Following its initiation role, DONSON also forms a part of the replisome during the elongation stage of DNA replication. Mutations in DONSON have recently been shown to lead to the Meier-Gorlin syndrome; this novel replication initiation role of DONSON therefore provides the explanation for the phenotypes caused by DONSON mutations in patients.
Topics: Humans; Cell Cycle Proteins; Chromatin; Congenital Microtia; Cyclin-Dependent Kinases; DNA Replication; Growth Disorders; Micrognathism; Minichromosome Maintenance Proteins; Patella; Replication Origin; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins
PubMed: 37638758
DOI: 10.1093/nar/gkad694 -
European Journal of Human Genetics :... Aug 2023High-throughput sequencing has become a standard first-tier approach for both diagnostics and research-based genetic testing. Consequently, this hypothesis-free... (Review)
Review
High-throughput sequencing has become a standard first-tier approach for both diagnostics and research-based genetic testing. Consequently, this hypothesis-free testing manner has revealed the true breadth of clinical features for many established genetic disorders, including Meier-Gorlin syndrome (MGORS). Previously known as ear-patella short stature syndrome, MGORS is characterized by growth delay, microtia, and patella hypo/aplasia, as well as genital abnormalities, and breast agenesis in females. Following the initial identification of genetic causes in 2011, a total of 13 genes have been identified to date associated with MGORS. In this review, we summarise the genetic and clinical findings of each gene associated with MGORS and highlight molecular insights that have been made through studying patient variants. We note interesting observations arising across this group of genes as the number of patients has increased, such as the unusually high number of synonymous variants affecting splicing in CDC45 and a subgroup of genes that also cause craniosynostosis. We focus on the complicated molecular genetics for DONSON, where we examine potential genotype-phenotype patterns using the first 3D structural model of DONSON. The canonical role of all proteins associated with MGORS are involved in different stages of DNA replication and in addition to summarising how patient variants impact on this process, we discuss the potential contribution of non-canonical roles of these proteins to the pathophysiology of MGORS.
Topics: Female; Humans; Congenital Microtia; Patella; Growth Disorders; Micrognathism
PubMed: 37059840
DOI: 10.1038/s41431-023-01359-z -
Developmental Dynamics : An Official... Aug 2020Mutations in core components of the spliceosome are responsible for a group of syndromes collectively known as spliceosomopathies. Patients exhibit microcephaly,... (Review)
Review
Mutations in core components of the spliceosome are responsible for a group of syndromes collectively known as spliceosomopathies. Patients exhibit microcephaly, micrognathia, malar hypoplasia, external ear anomalies, eye anomalies, psychomotor delay, intellectual disability, limb, and heart defects. Craniofacial malformations in these patients are predominantly found in neural crest cells-derived structures of the face and head. Mutations in eight genes SNRPB, RNU4ATAC, SF3B4, PUF60, EFTUD2, TXNL4, EIF4A3, and CWC27 are associated with craniofacial spliceosomopathies. In this review, we provide a brief description of the normal development of the head and the face and an overview of mutations identified in genes associated with craniofacial spliceosomopathies. We also describe a model to explain how and when these mutations are most likely to impact neural crest cells. We speculate that mutations in a subset of core splicing factors lead to disrupted splicing in neural crest cells because these cells have increased sensitivity to inefficient splicing. Hence, disruption in splicing likely activates a cellular stress response that includes increased skipping of regulatory exons in genes such as MDM2 and MDM4, key regulators of P53. This would result in P53-associated death of neural crest cells and consequently craniofacial malformations associated with spliceosomopathies.
Topics: Animals; Cell Cycle Proteins; Choanal Atresia; Craniofacial Abnormalities; Cyclophilins; DEAD-box RNA Helicases; Deafness; Disease Models, Animal; Eukaryotic Initiation Factor-4A; Exons; Facies; Heart Defects, Congenital; Humans; Intellectual Disability; Mice; Microcephaly; Micrognathism; Mutation; Neural Crest; Neuroepithelial Cells; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-mdm2; Psychomotor Disorders; RNA Splicing Factors; Ribonucleoprotein, U5 Small Nuclear; Spliceosomes; Syndrome; Tumor Suppressor Protein p53
PubMed: 32315467
DOI: 10.1002/dvdy.183 -
Genetics in Medicine : Official Journal... Jan 2023Craniofacial microsomia (CFM) represents a spectrum of craniofacial malformations, ranging from isolated microtia with or without aural atresia to underdevelopment of...
PURPOSE
Craniofacial microsomia (CFM) represents a spectrum of craniofacial malformations, ranging from isolated microtia with or without aural atresia to underdevelopment of the mandible, maxilla, orbit, facial soft tissue, and/or facial nerve. The genetic causes of CFM remain largely unknown.
METHODS
We performed genome sequencing and linkage analysis in patients and families with microtia and CFM of unknown genetic etiology. The functional consequences of damaging missense variants were evaluated through expression of wild-type and mutant proteins in vitro.
RESULTS
We studied a 5-generation kindred with microtia, identifying a missense variant in FOXI3 (p.Arg236Trp) as the cause of disease (logarithm of the odds = 3.33). We subsequently identified 6 individuals from 3 additional kindreds with microtia-CFM spectrum phenotypes harboring damaging variants in FOXI3, a regulator of ectodermal and neural crest development. Missense variants in the nuclear localization sequence were identified in cases with isolated microtia with aural atresia and found to affect subcellular localization of FOXI3. Loss of function variants were found in patients with microtia and mandibular hypoplasia (CFM), suggesting dosage sensitivity of FOXI3.
CONCLUSION
Damaging variants in FOXI3 are the second most frequent genetic cause of CFM, causing 1% of all cases, including 13% of familial cases in our cohort.
Topics: Humans; Goldenhar Syndrome; Congenital Microtia; Ear; Face; Micrognathism
PubMed: 36260083
DOI: 10.1016/j.gim.2022.09.005