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Journal of Cranio-maxillo-facial... Jan 2024The study aimed to evaluate the mid-term effect of MDO in children with Robin sequence (RS). In this case series, 13 patients with RS who underwent MDO were followed up...
The study aimed to evaluate the mid-term effect of MDO in children with Robin sequence (RS). In this case series, 13 patients with RS who underwent MDO were followed up for more than 5 years. Data were collected using clinical history and physical examination. Polysomnography was performed and endoscopic evaluations of the airway was performed if patients still presented obstructive signs of upper airways and/or dysphagia. The patients' clinical signs improved in the mid-term after versus before MDO (inspiratory noise, 92,3% vs 30,8%; apnea, 84,6% vs 7,7%; cyanosis, 76,9% vs 0%; desaturations, 69,2% vs 0%; and suprasternal/intercostal retractions, 61,5% vs 0%; p < 0.05). Statistically significant improvement was noted in the following polysomnographic parameters evaluated in the pre and postoperative mid-term: apnea-hypopnea index, total sleep time and desaturation index (p < 0.05). Within the limitations of the study it seems that MDO is an effective surgical option for children with RS, not only in the short term as previously demonstrated, but also in the mid-term.
Topics: Child; Humans; Infant; Polysomnography; Retrospective Studies; Pierre Robin Syndrome; Osteogenesis, Distraction; Apnea; Treatment Outcome; Mandible; Airway Obstruction
PubMed: 37884434
DOI: 10.1016/j.jcms.2023.08.004 -
The Journal of Pediatrics Feb 2024To describe the spectrum of disease and burden of care in infants with congenital micrognathia from a multicenter cohort hospitalized at tertiary care centers.
OBJECTIVE
To describe the spectrum of disease and burden of care in infants with congenital micrognathia from a multicenter cohort hospitalized at tertiary care centers.
STUDY DESIGN
The Children's Hospitals Neonatal Database was queried from 2010 through 2020 for infants diagnosed with micrognathia. Demographics, presence of genetic syndromes, and cleft status were summarized. Outcomes included death, length of hospitalization, neonatal surgery, and feeding and respiratory support at discharge.
RESULTS
Analysis included 3,236 infants with congenital micrognathia. Cleft palate was identified in 1266 (39.1%). A genetic syndrome associated with micrognathia was diagnosed during the neonatal hospitalization in 256 (7.9%). Median (IQR) length of hospitalization was 35 (16, 63) days. Death during the hospitalization (n = 228, 6.8%) was associated with absence of cleft palate (4.4%, P < .001) and maternal Black race (11.6%, P < .001). During the neonatal hospitalization, 1289 (39.7%) underwent surgery to correct airway obstruction and 1059 (32.7%) underwent gastrostomy tube placement. At the time of discharge, 1035 (40.3%) were exclusively feeding orally. There was significant variability between centers related to length of stay and presence of a feeding tube at discharge (P < .001 for both).
CONCLUSIONS
Infants hospitalized with congenital micrognathia have a significant burden of disease, commonly receive surgical intervention, and most often require tube feedings at hospital discharge. We identified disparities based on race and among centers. Development of evidence-based guidelines could improve neonatal care.
Topics: Infant; Child; Humans; Infant, Newborn; Micrognathism; Cleft Palate; Airway Obstruction; Intensive Care Units; North America; Retrospective Studies
PubMed: 37879601
DOI: 10.1016/j.jpeds.2023.113799 -
Journal of Clinical Sleep Medicine :... Jan 2024In growing children, temporomandibular joint (TMJ) ankylosis and septic arthritis are uncommon. Retrognathia and micrognathia affect airway patency and can cause...
UNLABELLED
In growing children, temporomandibular joint (TMJ) ankylosis and septic arthritis are uncommon. Retrognathia and micrognathia affect airway patency and can cause obstructive sleep apnea (OSA). No unified diagnostic criteria have been established for the management of this pathology. We describe the first case of treatment for pediatric TMJ ankylosis and severe OSA due to neonatal group B streptococcal septic TMJ arthritis. Untreated pathological changes in the TMJ will eventually lead to ankylosis. Among children, this will include facial growth disturbances leading to mandibular retrognathia, reduction in the oropharyngeal spaces, and OSA. Our patient had severe OSA with an apnea-hypopnea index of 24.9 events/h and oxygen saturation nadir of 73% as measured by polysomnography. She was treated successfully according to Andrade protocol. This is the first report of pediatric OSA due to TMJ ankylosis following neonatal group B streptococcal septic arthritis.
CITATION
Pesis M, Goldbart A, Givol N. Surgical correction of neonatal obstructive sleep apnea due to a temporomandibular joint ankylosis. . 2024;20(1):173-179.
Topics: Female; Infant, Newborn; Humans; Child; Mandible; Retrognathia; Osteogenesis, Distraction; Sleep Apnea, Obstructive; Micrognathism; Ankylosis; Temporomandibular Joint; Arthritis, Infectious
PubMed: 37811905
DOI: 10.5664/jcsm.10856 -
Indian Journal of Dental Research :... 2023SAMS syndrome is a rare genetic disorder characterized by midline facial clefting, skeletal anomalies, and other defects.
RATIONALE
SAMS syndrome is a rare genetic disorder characterized by midline facial clefting, skeletal anomalies, and other defects.
SALIENT FEATURES
Among the craniofacial manifestations of SAMS syndrome is the presence of a median mandibular cleft (MMC). MMC is a rare occurrence and in this syndrome, it poses a complex challenge for both functional and aesthetic reasons. Patient.
FINDINGS
This rare case report describes the successful correction of an MMC in an 18-month-old child diagnosed with SAMS syndrome.
TREATMENT
This report describes the presentation, diagnosis and treatment. The surgical intervention involved a meticulous, single stage, osseous reconstruction. The mechanism of MMC in SAMS syndrome is discussed.
OUTCOMES
Early intervention for MMC in SAMS syndrome patients can offer promising outcomes.
Topics: Humans; Infant; Cleft Palate; Face; Micrognathism; Syndrome
PubMed: 37787217
DOI: 10.4103/ijdr.ijdr_461_23 -
The Laryngoscope Apr 2024Surgically assisted rapid palatal expansion (SARPE) addresses transverse maxillary deficiency, a known contributor to nasal obstruction. The purpose of this study was to...
OBJECTIVE
Surgically assisted rapid palatal expansion (SARPE) addresses transverse maxillary deficiency, a known contributor to nasal obstruction. The purpose of this study was to assess the feasibility, preliminary outcomes, and safety of posterior palatal expansion via subnasal endoscopy (2PENN), a modified SARPE procedure, aimed at achieving anterior and posterior maxillary expansion.
METHODS
This prospective case series included consecutive adult patients with findings of transverse maxillary deficiency that underwent the 2PENN procedure from 4/2021 to 4/2022. Patients completed pre- and post-operative clinical evaluations, Nasal Obstruction and Septoplasty Effectiveness (NOSE) questionnaires, and computed tomography (CT), with measures including expansion at the level of the posterior nasal spine (PNS), first maxillary inter-molar distance (IMD), and anterior nasal spine (ANS).
RESULTS
The cohort (N = 20) was middle-aged (39 ± 11 years), predominantly male (80%), and overweight (BMI 28 ± 4 kg/m ). The majority (85%) of patients had sleep breathing issues, of which 10 (59%) had polysomnography-confirmed obstructive sleep apnea (OSA). Full anterior-posterior separation of the mid-palatal suture line was evident on all post-operative CT scans, with mean expansion at the PNS of 3.6 ± 1.3 mm, IMD of 6.1 ± 1.6 mm and ANS of 7.0 ± 1.6 mm (p < 0.001). Following surgery, mean NOSE scores improved from 57 ± 23 to 14 ± 13 (p < 0.001). One patient required maxillary antrostomy for post-operative sinusitis.
CONCLUSION
2PENN is an effective and safe technique for achieving both anterior and posterior maxillary expansion in patients with transverse maxillary deficiency. Further study is warranted to better understand the effect of 2PENN in patients with OSA, particularly as it relates to improving pharyngeal patency.
LEVEL OF EVIDENCE
4 Laryngoscope, 134:1970-1977, 2024.
Topics: Adult; Middle Aged; Humans; Male; Female; Palatal Expansion Technique; Pilot Projects; Nasal Obstruction; Sleep Apnea, Obstructive; Endoscopy, Gastrointestinal; Micrognathism; Maxilla
PubMed: 37772955
DOI: 10.1002/lary.31060 -
American Journal of Medical Genetics.... Sep 2023Heterozygous ARID1B variants result in Coffin-Siris syndrome. Features may include hypoplastic nails, slow growth, characteristic facial features, hypotonia,...
Heterozygous ARID1B variants result in Coffin-Siris syndrome. Features may include hypoplastic nails, slow growth, characteristic facial features, hypotonia, hypertrichosis, and sparse scalp hair. Most reported cases are due to ARID1B loss of function variants. We report a boy with developmental delay, feeding difficulties, aspiration, recurrent respiratory infections, slow growth, and hypotonia without a clinical diagnosis, where a previously unreported ARID1B missense variant was classified as a variant of uncertain significance. The pathogenicity of this variant was refined through combined methodologies including genome-wide methylation signature analysis (EpiSign), Machine Learning (ML) facial phenotyping, and LIRICAL. Trio exome sequencing and EpiSign were performed. ML facial phenotyping compared facial images using FaceMatch and GestaltMatcher to syndrome-specific libraries to prioritize the trio exome bioinformatic pipeline gene list output. Phenotype-driven variant prioritization was performed with LIRICAL. A de novo heterozygous missense variant, ARID1B p.(Tyr1268His), was reported as a variant of uncertain significance. The ACMG classification was refined to likely pathogenic by a supportive methylation signature, ML facial phenotyping, and prioritization through LIRICAL. The ARID1B genotype-phenotype has been expanded through an extended analysis of missense variation through genome-wide methylation signatures, ML facial phenotyping, and likelihood-ratio gene prioritization.
Topics: Male; Humans; DNA-Binding Proteins; Muscle Hypotonia; Transcription Factors; Face; Abnormalities, Multiple; Micrognathism; Intellectual Disability; Hand Deformities, Congenital; Neck
PubMed: 37654076
DOI: 10.1002/ajmg.c.32056 -
Clinical Dysmorphology Oct 2023
Topics: Humans; Mosaicism; Abnormalities, Multiple; Intellectual Disability; Micrognathism; DNA-Binding Proteins; Transcription Factors
PubMed: 37646735
DOI: 10.1097/MCD.0000000000000473 -
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 -
The FEBS Journal Jan 2024Although gene splicing occurs throughout the body, the phenotype of spliceosomal defects is largely limited to specific tissues. Cerebro-costo-mandibular syndrome (CCMS)...
Although gene splicing occurs throughout the body, the phenotype of spliceosomal defects is largely limited to specific tissues. Cerebro-costo-mandibular syndrome (CCMS) is one such spliceosomal disease, which presents as congenital skeletal dysmorphism and is caused by mutations of SNRPB gene encoding Small Nuclear Ribonucleoprotein Polypeptides B/B' (SmB/B'). This study employed in vitro cell cultures to monitor osteo- and chondro-differentiation and examined the role of SmB/B' in the differentiation process. We found that low levels of SmB/B' by knockdown or mutations of SNRPB led to suppressed osteodifferentiation in Saos-2 osteoprogenitor-like cells, which was accompanied by affected splicing of Dlx5. On the other hand, low SmB/B' led to promoted chondrogenesis in HEPM mesenchymal stem cells. Consistent with other reports, osteogenesis was promoted by the Wnt/β-catenin pathway activator and suppressed by Wnt and BMP blockers, whereas chondrogenesis was promoted by Wnt inhibitors. Suppressed osteogenic markers by SNRPB knockdown were partly rescued by Wnt/β-catenin pathway activation. Reporter analysis revealed that suppression of SNRPB results in attenuated Wnt pathway and/or enhanced BMP pathway activities. SNRPB knockdown altered splicing of TCF7L2 which impacts Wnt/β-catenin pathway activities. This work helps unravel the mechanism underlying CCMS whereby reduced expression of spliceosomal proteins causes skeletal phenotypes.
Topics: beta Catenin; Cell Differentiation; Spliceosomes; snRNP Core Proteins; Osteogenesis; Wnt Signaling Pathway; Cells, Cultured; Intellectual Disability; Micrognathism; Ribs
PubMed: 37584444
DOI: 10.1111/febs.16934 -
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