-
Stomatologiia 2024To study the effect of magnetic therapy on the formation of distraction regenerate of the lower jaw in patients with lower micrognathia.
PURPOSE
To study the effect of magnetic therapy on the formation of distraction regenerate of the lower jaw in patients with lower micrognathia.
MATERIALS AND METHODS
The study comprised 159 patients with inferior micrognathia of congenital and acquired etiology. The patients were divided into 2 groups. The main group consisted of 112 patients who received magnetic therapy: 55 patients with congenital micrognathia and 57 patients with acquired micrognathia. The control group included 47 patients who did not undergo magnetic therapy: 20 patients with congenital micrognathia and 27 patients with acquired micrognathia. Magnetic therapy was performed daily starting from day 1 or 2 after surgery. Ultrasound monitoring began on the 7th day of distraction and was carried out every 3-4 days, which made it possible to assess the dynamics of the formation of the distraction regenerate.
RESULTS
Ultrasound examination on the 7th day of distraction revealed that in the main group the number of distraction regenerates of the normotrophic type was 36.5%, hypotrophic type 18%, hypertrophic type 54.5%. In the control group, the corresponding rates were 53%, 31% and 22%.
CONCLUSION
Magnetic therapy induces osteogenesis and accelerates the maturation of the distraction regenerate. This makes it possible to accelerate the pace of distraction without reducing the quality of the regenerate.
Topics: Humans; Osteogenesis, Distraction; Male; Child; Female; Micrognathism; Magnetic Field Therapy; Child, Preschool; Mandible; Treatment Outcome
PubMed: 38904554
DOI: 10.17116/stomat202410303116 -
BMC Medical Genomics May 2024Coffin-Siris syndrome (CSS) is a rare autosomal dominant inheritance disorder characterized by distinctive facial features, hypoplasia of the distal phalanx or nail of...
Coffin-Siris syndrome (CSS) is a rare autosomal dominant inheritance disorder characterized by distinctive facial features, hypoplasia of the distal phalanx or nail of the fifth and additional digits, developmental or cognitive delay of varying degree, hypotonia, hirsutism/hypertrichosis, sparse scalp hair and varying kind of congenital anomalies. CSS can easily be misdiagnosed as other syndromes or disorders with a similar clinical picture because of their genetic and phenotypic heterogeneity. We describde the genotype-phenotype correlation of one patient from a healthy Chinese family with a novel genotype underlying CSS, who was first diagnosed in the ophthalmology department as early-onset high myopia (eoHM). Comprehensive ophthalmic tests as well as other systemic examinations were performed on participants to confirm the phenotype. The genotype was identified using whole exome sequencing, and further verified the results among other family members by Sanger sequencing. Real-time quantitative PCR (RT-qPCR) technology was used to detect the relative mRNA expression levels of candidate genes between proband and normal family members. The pathogenicity of the identified variant was determined by The American College of Medical Genetics and Genomics (ACMG) guidelines. STRING protein-protein interactions (PPIs) network analysis was used to detect the interaction of candidate gene-related proteins with high myopia gene-related proteins. The patient had excessive eoHM, cone-rod dystrophy, coarse face, excessive hair growth on the face, sparse scalp hair, developmental delay, intellectual disability, moderate hearing loss, dental hypoplasia, patent foramen ovale, chronic non-atrophic gastritis, bilateral renal cysts, cisterna magna, and emotional outbursts with aggression. The genetic assessment revealed that the patient carries a de novo heterozygous frameshift insertion variant in the ARID1B c.3981dup (p.Glu1328ArgfsTer5), which are strongly associated with the typical clinical features of CSS patients. The test results of RT-qPCR showed that mRNA expression of the ARID1B gene in the proband was approximately 30% lower than that of the normal control in the family, suggesting that the variant had an impact on the gene function at the level of mRNA expression. The variant was pathogenic as assessed by ACMG guidelines. Analysis of protein interactions in the STRING online database revealed that the ARID1A protein interacts with the high myopia gene-related proteins FGFR3, ASXL1, ERBB3, and SOX4, whereas the ARID1A protein antagonizes the ARID1B protein. Therefore, in this paper, we are the first to report a de novo heterozygous frameshift insertion variant in the ARID1B gene causing CSS with excessive eoHM. Our study extends the genotypic and phenotypic spectrums for ARID1B-CSS and supplies evidence of significant association of eoHM with variant in ARID1B gene. As CSS has high genetic and phenotypic heterogeneity, our findings highlight the importance of molecular genetic testing and an interdisciplinary clinical diagnostic workup to avoid misdiagnosis as some disorders with similar manifestations of CSS.
Topics: Humans; Intellectual Disability; Transcription Factors; Face; Male; Micrognathism; Pedigree; Female; Hand Deformities, Congenital; Myopia; DNA-Binding Proteins; Neck; Abnormalities, Multiple; Adult; Asian People; Genetic Association Studies; China; Phenotype; Exome Sequencing; Mutation; East Asian People
PubMed: 38790056
DOI: 10.1186/s12920-024-01904-9 -
Morphologie : Bulletin de L'Association... May 2024In addition to bone fragility, patients with osteogenesis imperfecta (OI) type III have typical craniofacial abnormalities, such as a triangular face and maxillary...
OBJECTIVES
In addition to bone fragility, patients with osteogenesis imperfecta (OI) type III have typical craniofacial abnormalities, such as a triangular face and maxillary micrognathism. However, in the osteogenesis imperfecta mouse (oim), a validated model of OI type III, few descriptions exist of craniofacial phenotype. Treatment of OI mostly consists of bisphosphonate administration. Cathepsin K inhibition has been tested as a promising therapeutic approach for osteoporosis and positive results were observed in long bones of cathepsin K knocked out oim (oim/CatK). This craniometry study aimed to highlight the craniofacial characteristics of oim and Cathepsin K KO mouse.
MATERIALS AND METHODS
We analyzed the craniofacial skeleton of 51 mice distributed in 4 genotype groups: Wt (control), oim, CatK, oim/CatK. The mice were euthanized at 13 weeks and their heads were analyzed using densitometric (pQCT), X-ray cephalometric, and histomorphometric methods.
RESULTS
The craniofacial skeleton of the oim mouse is frailer than the Wt one, with a reduced thickness and mineral density of the cranial vault and mandibular ramus. Different cephalometric data attest a dysmorphism similar to the one observed in humans with OI type III. Those abnormalities were not improved in the oim/CatK group.
CONCLUSION
These results suggest that oim mouse could serve as a complete model of the human OI type III, including the craniofacial skeleton. They also suggest that invalidation of cathepsin K has no impact on the craniofacial abnormalities of the oim model.
PubMed: 38788496
DOI: 10.1016/j.morpho.2024.100785 -
European Journal of Medical Genetics Jun 2024Anorectal malformations (ARMs) represent a wide spectrum of congenital anomalies of the anus and rectum, of which more than half are syndromic. Their etiology is highly... (Review)
Review
Anorectal malformations (ARMs) represent a wide spectrum of congenital anomalies of the anus and rectum, of which more than half are syndromic. Their etiology is highly heterogeneous and still poorly understood. We report a 4-year-old girl who initially presented with an isolated ARM, and subsequently developed a global developmental delay as part of an ARID1B-related Coffin-Siris syndrome (CSS). A co-occurrence of ARMs and CSS in an individual by chance is unexpected since both diseases are very rare. A review of the literature enabled us to identify 10 other individuals with both CSS and ARMs. Among the ten individuals reported in this study, 8 had a variant in ARID1A, 2 in ARID1B, and 1 in SMARCA4. This more frequent than expected association between CSS and ARM indicates that some ARMs are most likely part of the CSS spectrum, especially for ARID1A-related CSS.
Topics: Humans; Female; Micrognathism; Child, Preschool; Intellectual Disability; Transcription Factors; Neck; Hand Deformities, Congenital; Abnormalities, Multiple; DNA-Binding Proteins; Anorectal Malformations; Face; DNA Helicases; Nuclear Proteins; Anal Canal; Phenotype
PubMed: 38735569
DOI: 10.1016/j.ejmg.2024.104948 -
European Journal of Medical Genetics Jun 2024To date 11 patients with Coffin-Siris syndrome type 7 (OMIM 618027) have been described since the first literature report. All reported patients carried de novo variants...
To date 11 patients with Coffin-Siris syndrome type 7 (OMIM 618027) have been described since the first literature report. All reported patients carried de novo variants with presumed dominant negative effect, which localized in the PHD1/PHD2 domains of DPF2. Here we report on the first familial case of Coffin-Siris syndrome type 7. The index patient presented during the 1st year of life with failure to thrive and ectodermal anomalies. The genetic analysis using whole exome sequencing showed a likely pathogenic missense variant in the PHD1 region. The family analysis showed that the mother as well as the older brother of the index patient also carried the detected DPF2 variant in heterozygous state. The mother had a history of school difficulties but no history of failure to thrive and was overall mildly affected. The brother showed developmental delay with autistic features, ectodermal anomalies and overlapping morphologic features but did not have a history of growth failure problems. To our knowledge this is the first report of an inherited likely pathogenic variant in DPF2, underlining the variability of the associated phenotype as well as the importance of considering inherited DPF2 variants during the variant filtering strategy of whole exome data.
Topics: Adult; Female; Humans; Infant; Male; Abnormalities, Multiple; DNA-Binding Proteins; Face; Hand Deformities, Congenital; Intellectual Disability; Micrognathism; Mutation, Missense; Neck; Pedigree; Phenotype; Transcription Factors
PubMed: 38697389
DOI: 10.1016/j.ejmg.2024.104945 -
Clinical Oral Investigations Apr 2024Coffin-Siris Syndrome (CSS) is a congenital disorder characterized by delayed growth, dysmorphic facial features, hypoplastic nails and phalanges of the fifth digit, and...
OBJECTIVES
Coffin-Siris Syndrome (CSS) is a congenital disorder characterized by delayed growth, dysmorphic facial features, hypoplastic nails and phalanges of the fifth digit, and dental abnormalities. Tooth agenesis has been reported in CSS patients, but the mechanisms regulating this syndromic tooth agenesis remain largely unknown. This study aims to identify the pathogenic mutation of CSS presenting tooth genesis and explore potential regulatory mechanisms.
MATERIALS AND METHODS
We utilized whole-exome sequencing to identify variants in a CSS patient, followed by Sanger validation. In silico analysis including conservation analysis, pathogenicity predictions, and 3D structural assessments were carried out. Additionally, single-cell RNA sequencing and fluorescence in situ hybridization (FISH) were applied to explore the spatio-temporal expression of Sox4 expression during murine tooth development. Weighted Gene Co-expression Network Analysis (WGCNA) was employed to examine the functional role of SOX4.
RESULTS
A novel de novo SOX4 missense mutation (c.1255C > G, p.Leu419Val) was identified in a Chinese CSS patient exhibiting tooth agenesis. Single-cell RNA sequencing and FISH further verified high expression of Sox4 during murine tooth development, and WGCNA confirmed its central role in tooth development pathways. Enriched functions included cell-substrate junctions, focal adhesion, and RNA splicing.
CONCLUSIONS
Our findings link a novel SOX4 mutation to syndromic tooth agenesis in CSS. This is the first report of SOX4 missense mutation causing syndromic tooth agenesis.
CLINICAL RELEVANCE
This study not only enhances our understanding of the pathogenic mutation for syndromic tooth agenesis but also provides genetic diagnosis and potential therapeutic insights for syndromic tooth agenesis.
Topics: Animals; Female; Humans; Male; Mice; Abnormalities, Multiple; Anodontia; Exome Sequencing; Face; Hand Deformities, Congenital; In Situ Hybridization, Fluorescence; Intellectual Disability; Micrognathism; Mutation, Missense; Neck; SOXC Transcription Factors
PubMed: 38684576
DOI: 10.1007/s00784-024-05659-6 -
Clinical Oral Investigations Apr 2024Craniofacial anomalies are widely discussed as predisposing factors of breathing disorders. Since many more cofactors exist, this study investigated the association...
OBJECTIVE
Craniofacial anomalies are widely discussed as predisposing factors of breathing disorders. Since many more cofactors exist, this study investigated the association between maxillary micrognathia and morphological changes of posterior airway space and adenoids in these patients.
MATERIAL AND METHODS
Cephalometric radiographs of n = 73 patients were used for data acquisition. The patients were divided into two groups according to certain skeletal characteristics: maxillary micrognathia (n = 34, 16 female, 18 male; mean age 10.55 ± 3.03 years; defined by a SNA angle < 79°) and maxillary eugnathia (n = 39, 19 female, 20 male; mean age 10.93 ± 3.26 years; defined by a SNA angle > 79°). The evaluation included established procedures for measurements of the maxilla, posterior airway space and adenoids. Statistics included Kolmogorov-Smirnov-, T- and Mann-Whitney-U-Tests for the radiographs. The level of significance was set at p < 0.05.
RESULTS
The cephalometric analysis showed differences in the superior posterior face height and the depth of the posterior airway space at palatal level among the two groups. The depth of the posterior airway space at mandibular level was the same for both groups, just as the size of the area taken by adenoids in the nasopharynx.
CONCLUSIONS
Skeletal anomalies affect the dimension of the posterior airway space. There were differences among the subjects with maxillary micrognathia and these with a normal maxilla. However, the maxilla was only assessed in the sagittal direction, not in the transverse. This study showed that the morphology of the maxilla relates to the posterior airway space whereas the adenoids seem not to be affected.
CLINICAL RELEVANCE
Maxillary micrognathia is significantly associated with a smaller depth of the posterior airway space at the palatal level compared to patients with maxillary eugnathia.
Topics: Humans; Male; Female; Child; Adolescent; Adenoids; Micrognathism; Nasopharynx; Maxilla; Respiratory System; Cephalometry
PubMed: 38627272
DOI: 10.1007/s00784-024-05657-8 -
Molecular Genetics & Genomic Medicine Apr 2024Auriculocondylar syndrome (ARCND) is a rare congenital craniofacial developmental malformation syndrome of the first and second pharyngeal arches with external ear... (Review)
Review
BACKGROUND
Auriculocondylar syndrome (ARCND) is a rare congenital craniofacial developmental malformation syndrome of the first and second pharyngeal arches with external ear malformation at the junction between the lobe and helix, micromaxillary malformation, and mandibular condylar hypoplasia. Four subtypes of ARCND have been described so far, that is, ARCND1 (OMIM # 602483), ARCND2 (ARCND2A, OMIM # 614669; ARCND2B, OMIM # 620458), ARCND3 (OMIM # 615706), and ARCND4 (OMIM # 620457).
METHODS
This study reports a case of ARCND2 resulting from a novel pathogenic variant in the PLCB4 gene, and summarizes PLCB4 gene mutation sites and phenotypes of ARCND2.
RESULTS
The proband, a 5-day-old male neonate, was referred to our hospital for respiratory distress. Micrognathia, microstomia, distinctive question mark ears, as well as mandibular condyle hypoplasia were identified. Trio-based whole-exome sequencing identified a novel missense variant of NM_001377142.1:c.1928C>T (NP_001364071.1:p.Ser643Phe) in the PLCB4 gene, which was predicted to impair the local structural stability with a result that the protein function might be affected. From a review of the literature, only 36 patients with PLCB4 gene mutations were retrieved.
CONCLUSION
As with other studies examining familial cases of ARCND2, incomplete penetrance and variable expressivity were observed within different families' heterozygous mutations in PLCB4 gene. Although, motor and intellectual development are in the normal range in the vast majority of patients with ARCND2, long-term follow-up and assessment are still required.
Topics: Humans; Infant, Newborn; Male; China; Ear; Ear Diseases; Micrognathism; Phospholipase C beta; East Asian People
PubMed: 38618928
DOI: 10.1002/mgg3.2441 -
Paediatric Anaesthesia Jul 2024
Topics: Female; Humans; Abnormalities, Multiple; Delayed Emergence from Anesthesia; Face; Hand Deformities, Congenital; Intellectual Disability; Micrognathism; Neck; Infant
PubMed: 38586918
DOI: 10.1111/pan.14892 -
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