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The Journal of Craniofacial Surgery Oct 2021Oromandibular limb hypogenesis syndrome is a rare developmental anomaly and only a few cases are reported with complete surgical and orthodontic rehabilitation. An adult...
Oromandibular limb hypogenesis syndrome is a rare developmental anomaly and only a few cases are reported with complete surgical and orthodontic rehabilitation. An adult male patient with isolated hypoglossia, micrognathism, hypodontia, (oromandibular limb hypogenesis syndrome type I A) was treated with a combination of distraction osteogenesis and orthodontic intervention. The patient was followed up for the duration of 6 years from his first visit to 4 years after the surgery. The combined procedure resulted in successful and satisfactory treatment of the patient by restoring facial aesthetics, occlusal balance, and functional harmony. However, there was not enough tongue enlargement due to late surgical intervention. The objective of this report is to describe the etiology of hypoglossia, the consequences for oral function, and to share our experience from the oral rehabilitation during the treatment procedure.
Topics: Adult; Fingers; Humans; Male; Mandible; Micrognathism; Osteogenesis, Distraction; Stomatognathic System Abnormalities; Tongue
PubMed: 34015798
DOI: 10.1097/SCS.0000000000007669 -
Proceedings of the National Academy of... May 2021Loss-of-function mutations in chromatin remodeler gene are a cause of Coffin-Siris syndrome, a developmental disorder characterized by dysgenesis of corpus callosum....
Loss-of-function mutations in chromatin remodeler gene are a cause of Coffin-Siris syndrome, a developmental disorder characterized by dysgenesis of corpus callosum. Here, we characterize function during cortical development and find unexpectedly selective roles for in subplate neurons (SPNs). SPNs, strategically positioned at the interface of cortical gray and white matter, orchestrate multiple developmental processes indispensable for neural circuit wiring. We find that pancortical deletion of leads to extensive mistargeting of intracortical axons and agenesis of corpus callosum. Sparse deletion, however, does not autonomously misroute callosal axons, implicating noncell-autonomous functions in axon guidance. Supporting this possibility, the ascending axons of thalamocortical neurons, which are not autonomously affected by cortical deletion, are also disrupted in their pathfinding into cortex and innervation of whisker barrels. Coincident with these miswiring phenotypes, which are reminiscent of subplate ablation, we unbiasedly find a selective loss of SPN gene expression following deletion. In addition, multiple characteristics of SPNs crucial to their wiring functions, including subplate organization, subplate axon-thalamocortical axon cofasciculation ("handshake"), and extracellular matrix, are severely disrupted. To empirically test sufficiency in subplate, we generate a cortical plate deletion of that spares SPNs. In this model, subplate expression is sufficient for subplate organization, subplate axon-thalamocortical axon cofasciculation, and subplate extracellular matrix. Consistent with these wiring functions, subplate sufficiently enables normal callosum formation, thalamocortical axon targeting, and whisker barrel development. Thus, is a multifunctional regulator of subplate-dependent guidance mechanisms essential to cortical circuit wiring.
Topics: Abnormalities, Multiple; Animals; Cerebral Cortex; Chromatin; Connectome; Corpus Callosum; DNA-Binding Proteins; Face; Gene Deletion; Gene Expression Regulation; Gray Matter; Hand Deformities, Congenital; Humans; Intellectual Disability; Loss of Function Mutation; Mice; Mice, Transgenic; Micrognathism; Neck; Neural Pathways; Neurons; Thalamus; Transcription Factors; Vibrissae; White Matter
PubMed: 34011608
DOI: 10.1073/pnas.2100686118 -
BMC Pregnancy and Childbirth May 2021Meier-Gorlin syndrome 7 (MGS7) is a rare autosomal recessive condition. We reported a fetus diagnosed with Meier-Gorlin syndrome 7. The antenatal sonographic images were...
BACKGROUND
Meier-Gorlin syndrome 7 (MGS7) is a rare autosomal recessive condition. We reported a fetus diagnosed with Meier-Gorlin syndrome 7. The antenatal sonographic images were presented, and compound heterozygous mutations of CDC45 on chromosome 22 were identified by whole-exome sequencing (WES).
CASE PRESENTATION
Fetal growth restriction (FGR), craniosynostosis, and brachydactyly of right thumb were found in a fetus of 28th gestational weeks. The fetus was diagnosed as MGS7 clinically. After extensive counseling, the couple opted for prenatal diagnosis by cordocentesis and termination of pregnancy. Karyotype analysis and WES were performed. Chromosomal karyotyping showed that the fetus was 46, XY. There were 2 mutations of CDC45, the causal gene of MGS7 on chromosome 22, which were inherited from the couple respectively were identified by WES. Facial dysmorphism, brachydactyly of right thumb, and genitalia abnormally were proved by postpartum autopsy, and craniosynostosis was confirmed by three-dimensional computed tomography (3D-CT) reconstruction.
CONCLUSIONS
It is possible to detect multiple clinical features of Meier-Gorlin syndrome in prenatal sonography. Deteriorative FGR complicated with craniosynostosis indicates MGS7. Combination of 2D and 3D ultrasonography helps to detect craniosynostosis. The affected fetus was confirmed a compound heterozygote of CDC45 related MGS by whole-exome sequencing, which is critical in identifying rare genetic diseases.
Topics: Abortion, Induced; Asian People; China; Congenital Microtia; Female; Growth Disorders; Humans; Male; Micrognathism; Patella; Pregnancy; Pregnancy Trimester, Second; Ultrasonography, Prenatal; Young Adult
PubMed: 34000999
DOI: 10.1186/s12884-021-03868-5 -
Scientific Reports May 2021In children with mandibular hypoplasia, airway management is challenging. However, detailed cephalometric assessment data for this population are sparse. The aim of this... (Observational Study)
Observational Study
In children with mandibular hypoplasia, airway management is challenging. However, detailed cephalometric assessment data for this population are sparse. The aim of this study was to find risk factors for predicting difficult airways in children with mandibular hypoplasia, and compare upper airway anatomical differences using three-dimensional computed tomography (3D CT) between children with mandibular hypoplasia and demographically matched healthy controls. There were significant discrepancies in relative tongue position (P < 0.01) and anterior distance of the hyoid bone (P < 0.01) between patients with mandibular hypoplasia and healthy controls. All mandibular measures were significantly different between the two groups, except for the height of the ramus of the mandible. After adjusting for age and sex, the anterior distance of hyoid bone and inferior pogonial angle were significantly associated with a difficult airway (P = 0.01 and P = 0.02). Quantitative analysis of upper airway structures revealed significant discrepancies, including relative tongue position, hyoid distance, and mandible measures between patients with mandibular hypoplasia and healthy controls. The anterior distance of the hyoid bone and inferior pogonial angle may be risk factors for a difficult airway in patients with mandibular hypoplasia.
Topics: Airway Management; Case-Control Studies; Cephalometry; Child; Child, Preschool; Critical Illness; Female; Healthy Volunteers; Humans; Imaging, Three-Dimensional; Infant; Male; Mandible; Micrognathism; Risk Assessment; Risk Factors; Tomography, X-Ray Computed; Treatment Failure
PubMed: 33972643
DOI: 10.1038/s41598-021-89302-4 -
Anesthesia Progress Mar 2021Nicolaides-Baraitser syndrome (NCBRS) is a rare congenital genetic disorder characterized by distinctive facial features similar to Treacher Collins syndrome (TCS). We...
Nicolaides-Baraitser syndrome (NCBRS) is a rare congenital genetic disorder characterized by distinctive facial features similar to Treacher Collins syndrome (TCS). We report the first case of successful nasal fiberoptic intubation in a patient with NCBRS with micrognathia and limited mouth opening due to trismus. A 9-year-old girl with NCBRS and dental caries was scheduled to undergo general anesthesia for a dental extraction. Initial attempts at oral intubation using a video laryngoscope were unsuccessful. However, subsequent attempts at nasal intubation using a flexible fiberoptic scope were successful. This report highlights that patients with NCBRS may present with difficult airways to manage and intubate.
Topics: Airway Management; Child; Dental Caries; Facies; Female; Foot Deformities, Congenital; Humans; Hypotrichosis; Intellectual Disability; Intubation, Intratracheal; Micrognathism; Mouth
PubMed: 33827121
DOI: 10.2344/anpr-67-04-05 -
Stem Cell Research May 2021Germline missense mutations in the BAF swi/snf chromatin remodeling subunit SMARCA4 are associated with neurodevelopmental disorders, including Coffin Siris Syndrome...
Germline missense mutations in the BAF swi/snf chromatin remodeling subunit SMARCA4 are associated with neurodevelopmental disorders, including Coffin Siris Syndrome (CSS). Here, we generated an induced pluripotent stem cell line from a male patient with atypical CSS features and a de novo heterozygous missense mutation in the SMARCA4 gene (c.3607C>T, p.(Arg1203Cys)). Hair root derived keratinocytes were reprogrammed using non-integrative Sendai virus vector delivery of pluripotency factors. iPSCs generated display normal morphology and molecular karyotype, express pluripotency markers and are able to differentiate into the three germ layers.
Topics: Abnormalities, Multiple; Autism Spectrum Disorder; DNA Helicases; Face; Germ Cells; Hand Deformities, Congenital; Humans; Induced Pluripotent Stem Cells; Intellectual Disability; Male; Micrognathism; Mutation; Mutation, Missense; Neck; Nuclear Proteins; Transcription Factors
PubMed: 33799280
DOI: 10.1016/j.scr.2021.102304 -
European Journal of Human Genetics :... Jan 2022Here we report for the first time on the maternal transmission of mild Coffin-Siris syndrome (CSS) caused by a SOX11 missense variant. We present two sisters with...
Here we report for the first time on the maternal transmission of mild Coffin-Siris syndrome (CSS) caused by a SOX11 missense variant. We present two sisters with intellectual disability and muscular hypotonia born to non-consanguineous parents. Cogan ocular motor apraxia was present in both sisters. Body measurements were in a normal range. The mother and both daughters showed hypoplastic nails of the fifth toes. A missense variant in SOX11 [c.139 G > A; p.(Gly47Ser)] in both sisters and their mother was identified. Since 2014, variants in SOX11 are known to cause mild CSS. Most described patients showed intellectual disability, especially concerning acquired language. All of them had hypoplastic nails of the fifth toes. It is of note, that some of these patients show Cogan ocular motor apraxia. The facial dysmorphic features seem not to be specific. We suggest that the combination of Cogan ocular motor apraxia, hypoplastic nails of fifth toes, and developmental delay give the important diagnostic clue for a variant in the SOX11 gene (OMIM 615866, MR 27).
Topics: Abnormalities, Multiple; Adult; Child; Face; Female; Hand Deformities, Congenital; Humans; Intellectual Disability; Micrognathism; Mutation, Missense; Neck; Pedigree; Phenotype; SOXC Transcription Factors
PubMed: 33785884
DOI: 10.1038/s41431-021-00865-2 -
Journal of Human Genetics Oct 2021Auriculocondylar syndrome (ARCND) is an autosomal monogenic disorder characterised by external ear abnormalities and micrognathia due to hypoplasia of the mandibular...
Auriculocondylar syndrome (ARCND) is an autosomal monogenic disorder characterised by external ear abnormalities and micrognathia due to hypoplasia of the mandibular rami, condyle and coronoid process. Genetically, three subtypes of ARCND (ARCND1, ARCND2 and ARCND3) have been reported. To date, five pathogenic variants of GNAI3 have been reported in ARCND1 patients. Here, we report a novel variant of GNAI3 (NM_006496:c.807C>A:p.(Asn269Lys)) in a Japanese girl with micrognathia using trio-based whole exome sequencing analysis. The GNAI3 gene encodes a heterotrimeric guanine nucleotide-binding protein. The novel variant locates the guanine nucleotide-binding site, and the substitution was predicted to interfere with guanine nucleotide-binding by in silico structural analysis. Three-dimensional computer tomography scan, or cephalogram, displayed severely hypoplastic mandibular rami and fusion to the medial and lateral pterygoid plates, which have been recognised in other ARCND1 patients, but have not been described in ARCND2 and ARCND3, suggesting that these may be distinguishable features in ARCND1.
Topics: Child, Preschool; Ear; Ear Diseases; Female; GTP-Binding Protein alpha Subunits, Gi-Go; Humans; Mandible; Micrognathism; Mutation, Missense; Pedigree; Phenotype; Exome Sequencing
PubMed: 33723370
DOI: 10.1038/s10038-021-00915-z -
European Journal of Human Genetics :... Jul 2021The MCM2-7 helicase is a heterohexameric complex with essential roles as part of both the pre-replication and pre-initiation complexes in the early stages of DNA...
The MCM2-7 helicase is a heterohexameric complex with essential roles as part of both the pre-replication and pre-initiation complexes in the early stages of DNA replication. Meier-Gorlin syndrome, a rare primordial dwarfism, is strongly associated with disruption to the pre-replication complex, including a single case described with variants in MCM5. Conversely, a biallelic pathogenic variant in MCM4 underlies immune deficiency with growth retardation, features also seen in individuals with pathogenic variants in other pre-initiation complex encoding genes such as GINS1, MCM10, and POLE. Through exome and chromium genome sequencing, supported by functional studies, we identify biallelic pathogenic variants in MCM7 and a strong candidate biallelic pathogenic variant in MCM3. We confirm variants in MCM7 are deleterious and through interfering with MCM complex formation, impact efficiency of S phase progression. The associated phenotypes are striking; one patient has typical Meier-Gorlin syndrome, whereas the second case has a multi-system disorder with neonatal progeroid appearance, lipodystrophy and adrenal insufficiency. We provide further insight into the developmental complexity of disrupted MCM function, highlighted by two patients with a similar variant profile in MCM7 but disparate clinical features. Our results build on other genetic findings linked to disruption of the pre-replication and pre-initiation complexes, and the replisome, and expand the complex clinical genetics landscape emerging due to disruption of DNA replication.
Topics: Adolescent; Adrenal Insufficiency; Alleles; Amino Acid Sequence; Cell Cycle; Child; Child, Preschool; Congenital Microtia; Facies; Female; Genetic Association Studies; Genetic Predisposition to Disease; Genetic Variation; Genotype; Growth Disorders; Humans; Infant; Lipodystrophy; Male; Micrognathism; Minichromosome Maintenance Complex Component 3; Minichromosome Maintenance Complex Component 7; Models, Molecular; New Zealand; Patella; Phenotype; Protein Conformation
PubMed: 33654309
DOI: 10.1038/s41431-021-00839-4 -
Development (Cambridge, England) Feb 2021Ciliopathies represent a growing class of diseases caused by defects in microtubule-based organelles called primary cilia. Approximately 30% of ciliopathies are...
Ciliopathies represent a growing class of diseases caused by defects in microtubule-based organelles called primary cilia. Approximately 30% of ciliopathies are characterized by craniofacial phenotypes such as craniosynostosis, cleft lip/palate and micrognathia. Patients with ciliopathic micrognathia experience a particular set of difficulties, including impaired feeding and breathing, and have extremely limited treatment options. To understand the cellular and molecular basis for ciliopathic micrognathia, we used the ( ), a bona fide avian model for the human ciliopathy oral-facial-digital syndrome subtype 14. Histological analyses revealed that the onset of ciliopathic micrognathia in embryos occurred at the earliest stages of mandibular development. Neural crest-derived skeletal progenitor cells were particularly sensitive to a ciliopathic insult, undergoing unchecked passage through the cell cycle and subsequent increased proliferation. Furthermore, whereas neural crest-derived skeletal differentiation was initiated, osteoblast maturation failed to progress to completion. Additional molecular analyses revealed that an imbalance in the ratio of bone deposition and resorption also contributed to ciliopathic micrognathia in embryos. Thus, our results suggest that ciliopathic micrognathia is a consequence of multiple aberrant cellular processes necessary for skeletal development, and provide potential avenues for future therapeutic treatments.
Topics: Animals; Bone Remodeling; Bone Resorption; Cell Cycle; Ciliopathies; Craniofacial Abnormalities; Disease Susceptibility; Embryo, Nonmammalian; Gene Expression Regulation, Developmental; Genetic Association Studies; Hedgehog Proteins; Micrognathism; Organogenesis; Osteoblasts; Phenotype; Zinc Finger Protein GLI1
PubMed: 33589509
DOI: 10.1242/dev.194175