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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 -
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 -
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 -
Otolaryngologic Clinics of North America Aug 2024Oral causes of dysphagia in infancy may involve the lips, the tongue, or the palate. Whereas ankyloglossia is commonly diagnosed in infants with dysphagia, assessment of... (Review)
Review
Oral causes of dysphagia in infancy may involve the lips, the tongue, or the palate. Whereas ankyloglossia is commonly diagnosed in infants with dysphagia, assessment of the need for surgical intervention may be less straightforward. Tongue size (macroglossia) may be associated with dysphagia as it may cause limitation of movement of the food or milk bolus by the lips or cheeks. Congenital conditions such as cleft lip and palate, micrognathia, or craniofacial microsomia may also be associated with dysphagia. Diagnosis and treatment of these conditions can be improved with the engagement of lactation and feeding experts as well as multidisciplinary craniofacial teams.
Topics: Humans; Deglutition Disorders; Infant; Tongue; Child; Ankyloglossia; Cleft Palate; Cleft Lip; Lip; Mouth Abnormalities; Micrognathism
PubMed: 38503668
DOI: 10.1016/j.otc.2024.02.012 -
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 -
NeoReviews Nov 2023
Topics: Pregnancy; Female; Humans; Micrognathism; Prenatal Diagnosis; Ultrasonography, Prenatal
PubMed: 37907406
DOI: 10.1542/neo.24-11-e753 -
International Journal of Gynaecology... Dec 2023Treacher Collins syndrome (TCS) should be suspected if the triad of micrognathia, glossoptosis, and posterior cleft palate, and deformed external ears are observed... (Review)
Review
Treacher Collins syndrome (TCS) should be suspected if the triad of micrognathia, glossoptosis, and posterior cleft palate, and deformed external ears are observed during prenatal ultrasonography, excepting Pierre Robin sequence. Visualization of the fetal zygomatic bone and down-slanting palpebral fissures are conducive to differentiation. Molecular genetics testing can establish a definite diagnosis. A 28-year-old pregnant Chinese woman was referred for systematic ultrasound examination at 24 weeks. Two-dimensional and three-dimensional ultrasound showed polyhydramnios, micrognathia, absence of nasal bone, microtia, secondary cleft palate, mandibular hypoplasia, glossoptosis, and normal limbs and vertebrae. Pierre Robin sequence was misdiagnosed with the triad of micrognathia, glossoptosis, and posterior cleft palate. Final diagnosis of TCS was confirmed by whole-exome sequencing. Visualization of the fetal zygomatic bone and down-slanting palpebral fissures can facilitate a differential diagnosis between Pierre Robin sequence and TCS, with the triad of micrognathia, glossoptosis, and posterior cleft palate.
Topics: Pregnancy; Female; Humans; Adult; Mandibulofacial Dysostosis; Pierre Robin Syndrome; Micrognathism; Glossoptosis; Cleft Palate; Prenatal Diagnosis
PubMed: 37231986
DOI: 10.1002/ijgo.14881 -
Human Genetics Jan 2024Coffin-Siris syndrome (CSS) is a rare multisystemic autosomal dominant disorder. Since 2012, alterations in genes of the SWI/SNF complex were identified as the molecular...
Coffin-Siris syndrome (CSS) is a rare multisystemic autosomal dominant disorder. Since 2012, alterations in genes of the SWI/SNF complex were identified as the molecular basis of CSS, studying largely pediatric cohorts. Therefore, there is a lack of information on the phenotype in adulthood, particularly on the clinical outcome in adulthood and associated risks. In an international collaborative effort, data from 35 individuals ≥ 18 years with a molecularly ascertained CSS diagnosis (variants in ARID1B, ARID2, SMARCA4, SMARCB1, SMARCC2, SMARCE1, SOX11, BICRA) using a comprehensive questionnaire was collected. Our results indicate that overweight and obesity are frequent in adults with CSS. Visual impairment, scoliosis, and behavioral anomalies are more prevalent than in published pediatric or mixed cohorts. Cognitive outcomes range from profound intellectual disability (ID) to low normal IQ, with most individuals having moderate ID. The present study describes the first exclusively adult cohort of CSS individuals. We were able to delineate some features of CSS that develop over time and have therefore been underrepresented in previously reported largely pediatric cohorts, and provide recommendations for follow-up.
Topics: Adult; Humans; Child; Intellectual Disability; Abnormalities, Multiple; Micrognathism; Hand Deformities, Congenital; Neck; Phenotype; DNA Helicases; Nuclear Proteins; Transcription Factors; Chromosomal Proteins, Non-Histone; DNA-Binding Proteins; Face
PubMed: 38117302
DOI: 10.1007/s00439-023-02622-5 -
Genes Dec 2023Nager syndrome is a rare human developmental disorder characterized by craniofacial defects including the downward slanting of the palpebral fissures, cleft palate, limb... (Review)
Review
Nager syndrome is a rare human developmental disorder characterized by craniofacial defects including the downward slanting of the palpebral fissures, cleft palate, limb deformities, mandibular hypoplasia, hypoplasia or absence of thumbs, microretrognathia, and ankylosis of the temporomandibular joint. The prevalence is very rare and the literature describes only about a hundred cases of Nager syndrome. There is evidence of autosomal dominant and autosomal recessive inheritance for Nager syndrome, suggesting genetic heterogeneity. The majority of the described causes of Nager syndrome include pathogenic variants in the gene, which encodes a component of the spliceosome; therefore, the syndrome belongs to the spliceosomopathy group of diseases. The diagnosis is made on the basis of physical and radiological examination and detection of mutations in the gene. Due to the diversity of defects associated with Nager syndrome, patients require multidisciplinary, complex, and long-lasting treatment. Usually, it starts from birth until the age of twenty years. The surgical procedures vary over a patient's lifetime and are related to the needed function. First, breathing and feeding must be facilitated; then, oral and facial clefts should be addressed, followed by correcting eyelid deformities and cheekbone reconstruction. In later age, a surgery of the nose and external ear is performed. Speech and hearing disorders require specialized logopedic treatment. A defect of the thumb is treated by transplanting a tendon and muscle or transferring the position of the index finger. In addition to surgery, in order to maximize a patient's benefit and to reduce functional insufficiency, complementary treatments such as rehabilitation and physiotherapy are recommended. In our study, we describe eight patients of different ages with various cases of Nager syndrome. The aim of our work was to present the actual genetic knowledge on this disease and its treatment procedures.
Topics: Child; Humans; Young Adult; Adult; Mandibulofacial Dysostosis; Cleft Palate; Micrognathism; Syndrome; RNA Splicing Factors
PubMed: 38254920
DOI: 10.3390/genes15010029 -
Clinical Genetics Sep 2023Pigmentary abnormalities in Coffin-Siris Syndrome should be considered as part of the wide phenotypical spectrum of this patients.
Pigmentary abnormalities in Coffin-Siris Syndrome should be considered as part of the wide phenotypical spectrum of this patients.
Topics: Humans; Syndrome; Abnormalities, Multiple; Intellectual Disability; Micrognathism; Hand Deformities, Congenital; Neck; Pigmentation
PubMed: 37166055
DOI: 10.1111/cge.14356