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Annals of Plastic Surgery Jan 2022Mandibular distraction osteogenesis (MDO) effectively treats tongue-based airway obstruction (TBAO) in micrognathic patients with Robin Sequence. Mandibular distraction...
PURPOSE
Mandibular distraction osteogenesis (MDO) effectively treats tongue-based airway obstruction (TBAO) in micrognathic patients with Robin Sequence. Mandibular distraction osteogenesis may also address TBAO in certain nonmicrognathic patients who have severe obstructive apnea, although there is no current literature to guide MDO use in these atypical patients. This study describes outcomes of MDO in a series of patients with TBAO without micrognathia.
METHODS
Patients who underwent MDO for TBAO from 2013-20 were reviewed, and patients with micrognathia were excluded. Study subjects received baseline/follow up polysomnography. Polysomnography variables, including Obstructive Apnea Hypopnea Index, oxyhemoglobin saturation nadir (SpO2 nadir), percent sleep time end tidal CO2 greater than 50 mm Hg (%ETCO2 > 50), and respiratory-related arousals were compared before and after MDO. Demographics, syndromic/cleft palate status, airway anomalies, respiratory support, and feeding outcomes were collected.
RESULTS
One hundred and twenty-four patients underwent MDO during this study period; 5 were nonmicrognathic and included in analysis. Sixty percent (n = 3) of the cohort was syndromic: 1 patient each had Trisomy 9, Beckwith Wiedemann syndrome, and duplicated pituitary gland plus syndrome. Forty percent (n = 2) of patients had a cleft palate, 60% (n = 3) had laryngomalacia, and 40% had tracheomalacia. Median (range) age at MDO was 53 days (47-167 days), and median length of distraction was 16 mm (14-20 mm). After MDO, median Obstructive Apnea Hypopnea Index decreased from x̃ = 60.7/h (11.6-109.4) to x̃ = 5.3/h (3.5-19.3) (P = 0.034). SpO2 nadir increased (69% [58-74] to 85% [80-88], P = 0.011), and median %ETCO2 > 50 mm Hg decreased (5.8% [5.2-30.1] to 0.0% [0.0-1.3], P ≤ 0.043). Continuous positive airway pressure was used by all patients immediately after MDO, and at 6 months postoperatively, 1 patient remained on continuous positive airway pressure and 1 patient required supplemental oxygen. At last follow up, no patients had significant residual airway obstruction or required a tracheostomy.
CONCLUSIONS
Mandibular distraction osteogenesis can effectively treat severe TBAO in some patients without micrognathia that would otherwise be candidates for tracheostomy. When used in select patients, MDO significantly improves obstructive sleep apnea and reduces need for ventilatory support, although feeding support is still needed in most patients at 6 months. Further study in a larger cohort will help identify appropriate candidates for MDO and characterize outcomes of unique patient populations.
Topics: Airway Obstruction; Humans; Infant; Mandible; Micrognathism; Osteogenesis, Distraction; Oxygen Saturation; Pierre Robin Syndrome; Retrospective Studies; Tongue; Treatment Outcome
PubMed: 34176894
DOI: 10.1097/SAP.0000000000002891 -
American Journal of Medical Genetics.... Sep 2014Evidence is now accumulating from a number of sequencing studies that ARID1B not only appears to be one of the most frequently mutated intellectual disability (ID)... (Review)
Review
Evidence is now accumulating from a number of sequencing studies that ARID1B not only appears to be one of the most frequently mutated intellectual disability (ID) genes, but that the range of phenotypes caused by ARID1B mutations seems to be extremely wide. Thus, it is one of the most interesting ID genes identified so far in the exome sequencing era. In this article, we review the literature surrounding ARID1B and attempt to delineate the ARID1B phenotype. The vast majority of published ARID1B patients have been ascertained through studies of Coffin-Siris syndrome (CSS), which leads to bias when documenting the frequencies of phenotypic features. Additional observations of those individuals ascertained through exome sequencing studies helps in delineation of the broader clinical phenotype. We are currently establishing an ARID1B consortium, aimed at collecting ARID1B patients identified through genome-wide sequencing strategies. We hope that this endeavor will eventually lead to a more comprehensive view of the ARID1B phenotype.
Topics: Abnormalities, Multiple; DNA-Binding Proteins; Face; Genetic Association Studies; Hand Deformities, Congenital; Humans; Intellectual Disability; Micrognathism; Mutation; Neck; Transcription Factors
PubMed: 25169814
DOI: 10.1002/ajmg.c.31414 -
International Journal of Pediatric... Jun 2016Mandibular distraction osteogenesis (MDO) is becoming increasingly more commonly used as in neonates and infants with upper airway obstruction secondary to micrognathia.... (Review)
Review
UNLABELLED
Mandibular distraction osteogenesis (MDO) is becoming increasingly more commonly used as in neonates and infants with upper airway obstruction secondary to micrognathia. A significant number of these children are dependent on nasoenteric feeding or gastrostomies after birth for adequate nutrition and often suffer from gastro-esophageal reflux (GERD).
OBJECTIVE
This analysis is a subset of a larger systematic review. The objective of this study is to determine the effects of MDO on feeding and GERD.
DATA SOURCES
The databases searched included PubMed, Embase, Scopus, Web of Knowledge and grey literature sources.
STUDY SELECTION
The inclusion criterion included studies in children with clinical evidence of micrognathia/Pierre Robin Sequence (PRS) who have failed conservative treatments, including both syndromic (sMicro) and non-syndromic (iPRS) patients. 21 studies relevant to feeding and 4 studies relevant to GERD outcomes were included. All studies included were case series and case reports.
RESULTS
MDO leads to a significant improvement in feeding, with 82% of children feeding exclusively orally after surgery. The overall percentage of children with iPRS who were feeding orally was 93.7% compared with only 72.9% in the sMicro group (p<0.004). A growth decline within the first six weeks after surgery was observed in multiple studies. Overall, out of 70 patients with pre-operative GERD, only four had evidence of GERD after surgery.
CONCLUSIONS
Considering the limitations of this systematic review, this study found that successful relief of airway obstruction by MDO leads to improvement of feeding and improvement in symptoms of GERD in children with upper airway obstruction secondary to micrognathia. Clinicians need to be aware of the risk of growth decline in the initial post-operative period.
Topics: Airway Obstruction; Child; Eating; Feeding Behavior; Gastroesophageal Reflux; Humans; Infant; Infant, Newborn; Mandible; Micrognathism; Osteogenesis, Distraction; Pierre Robin Syndrome; Postoperative Period; Treatment Outcome
PubMed: 27240511
DOI: 10.1016/j.ijporl.2016.03.033 -
Seminars in Fetal & Neonatal Medicine Dec 2021Evaluation and management of airway obstruction in prone position were reviewed from studies in infants with micrognathia and/or cleft palate, using polysomnography... (Review)
Review
Evaluation and management of airway obstruction in prone position were reviewed from studies in infants with micrognathia and/or cleft palate, using polysomnography (PSG) or similar measures, and comparing prone against other positions. Most studies identified were case series from specialist referral centres. Airway obstruction appears more severe on PSG than clinical assessment, but there is no consensus for PSG definitions of mild, moderate or severe airway obstruction. Infants show individual variability in responses to positioning; sleep quality tends to improve when prone, but 22-25% have better respiratory outcomes when supine. Most centres recommend home monitoring if advising that an infant be placed prone to manage their airway obstruction. In conclusion, in case series, success rates for managing infant airway obstruction by prone positioning vary from 12 to 76%. PSG studies comparing prone with other sleep positions can help differentiate which infants show improved airway obstruction and/or sleep quality when positioned prone.
Topics: Airway Obstruction; Conservative Treatment; Humans; Infant; Micrognathism; Pierre Robin Syndrome; Polysomnography
PubMed: 34742665
DOI: 10.1016/j.siny.2021.101282 -
Zhonghua Kou Qiang Yi Xue Za Zhi =... Jan 2021Maxillary transverse deficiency is one of the critical manifestations of malocclusion. It is of vital importance to diagnose maxillary transverse deficiency at the early... (Review)
Review
Maxillary transverse deficiency is one of the critical manifestations of malocclusion. It is of vital importance to diagnose maxillary transverse deficiency at the early stage because maxillary development in the transverse dimension stops early. Currently, there are several approaches to diagnose maxillary transverse deficiency, including clinical examination, dental cast measurement, poster-anterior cephalogram, and cone-beam CT. This narrative review will review these diagnostic and predictive approaches of maxillary transverse deficiency.
Topics: Cephalometry; Cone-Beam Computed Tomography; Humans; Malocclusion; Maxilla; Micrognathism; Palatal Expansion Technique; Tooth
PubMed: 34645245
DOI: 10.3760/cma.j.cn112144-20200526-00297 -
American Journal of Medical Genetics.... Jan 2023Coffin-Siris syndrome (CSS, MIM135900) is a rare multiple congenital anomaly syndrome caused by pathogenic variants in the BAF complex; up to 28% of patients have... (Review)
Review
Coffin-Siris syndrome (CSS, MIM135900) is a rare multiple congenital anomaly syndrome caused by pathogenic variants in the BAF complex; up to 28% of patients have previously been reported to have seizures, however, a comprehensive review of epilepsy has not been undertaken in this population. The International CSS Patient Report Database was queried for patients with self-reported seizures, epilepsy, and EEG results. Data gathered included demographic data, pathogenic gene variants, seizure characteristics and treatments, and EEG findings. In addition, a PubMed search was performed using keywords "Coffin-Siris syndrome" and "epilepsy," "seizures," or "EEG." Results from relevant papers are reported. Twenty-four (7.2%) of 334 patients in the database reported having seizures, EEG abnormalities, and/or epilepsy. Median age of seizure onset was 2. 7 years. Fifteen of the 23 patients with seizures or epilepsy had an ARID1B causative variant. Seventeen patients (5.1%) reported EEG abnormalities, the majority of which were described as focal or multifocal (87.5%). In all but one patient, seizures were controlled on antiseizure medications (ASMs). The literature review yielded 311 unique CSS patients, 82 of which (26.4%) carried diagnoses of seizures or epilepsy. Details on seizure type(s), EEG findings, and response to treatment were limited.
Topics: Humans; Micrognathism; Hand Deformities, Congenital; DNA-Binding Proteins; Intellectual Disability; Face; Neck; Genetic Association Studies; Abnormalities, Multiple; Epilepsy; Seizures
PubMed: 36177969
DOI: 10.1002/ajmg.a.62979 -
Developmental Dynamics : An Official... Apr 2021Previous studies showed that mice lacking Fgf18 function had cleft palate defects and that the FGF18 locus was associated with cleft lip and palate in humans, but what...
BACKGROUND
Previous studies showed that mice lacking Fgf18 function had cleft palate defects and that the FGF18 locus was associated with cleft lip and palate in humans, but what specific roles Fgf18 plays during palatogenesis are unclear.
RESULTS
We show that Fgf18 exhibits regionally restricted expression in developing palatal shelves, mandible, and tongue, during palatal outgrowth and fusion in mouse embryos. Tissue-specific inactivation of Fgf18 throughout neural crest-derived craniofacial mesenchyme caused shortened mandible and reduction in ossification of the frontal, nasal, and anterior cranial base skeletal elements in Fgf18 ;Wnt1-Cre mutant mice. About 64% of Fgf18 ;Wnt1-Cre mice exhibited cleft palate. Whereas palatal shelf elevation was impaired in many Fgf18 ;Wnt1-Cre embryos, no significant difference in palatal cell proliferation was detected between Fgf18 ;Wnt1-Cre embryos and their control littermates. Embryonic maxillary explants from Fgf18 ;Wnt1-Cre embryos showed successful palatal shelf elevation and fusion in organ culture similar to the maxillary explants from control embryos. Furthermore, tissue-specific inactivation of Fgf18 in the early palatal mesenchyme did not cause cleft palate.
CONCLUSION
These results demonstrate a critical role for Fgf18 expression in the neural crest-derived mesenchyme for the development of the mandible and multiple craniofacial bones but Fgf18 expression in the palatal mesenchyme is dispensable for palatogenesis.
Topics: Animals; Cleft Palate; Female; Fibroblast Growth Factors; Male; Mandible; Mesoderm; Mice, Knockout; Micrognathism; Neural Crest; Palate; Mice
PubMed: 33034111
DOI: 10.1002/dvdy.259 -
American Journal of Medical Genetics.... Oct 2020Coffin-Siris syndrome (CSS; OMIM #135900) is a rare, multisystem syndrome caused by pathogenic variants in genes encoding the BRG-1 associated factors complex (BAF)....
Coffin-Siris syndrome (CSS; OMIM #135900) is a rare, multisystem syndrome caused by pathogenic variants in genes encoding the BRG-1 associated factors complex (BAF). Individuals with CSS often present with feeding difficulties and failure to thrive during infancy, in addition to a number of variable congenital anomalies. Nutritional interventions are used to support growth in this population, and growth hormone therapy has been reported in a limited number of cases. The purpose of this study was to construct CSS-specific growth charts to better characterize the growth in this population. Anthropometric data were collected from 99 individuals enrolled in the CSS/BAF pathway international registry via a retrospective chart review. All measurements obtained after the first exposure to growth hormone therapy were excluded from this analysis. Sex-specific centiles (5th, 50th, and 95th) were estimated for height, weight, and head circumference from birth to age 10. Cubic smoothing splines were then fit to the centile estimates and superimposed on normative male and female growth curves for comparison. The CSS patients in this cohort exhibited normal growth parameters at birth. By age 10, the weight and head circumference of the CSS cohort began to approach normal parameters. Stature, however, remained shortened at 10 years of age.
Topics: Abnormalities, Multiple; Child; Child, Preschool; DNA Helicases; Face; Female; Genetic Association Studies; Genetic Predisposition to Disease; Growth Charts; Hand Deformities, Congenital; Humans; Infant; Infant, Newborn; Intellectual Disability; Male; Micrognathism; Neck; Nuclear Proteins; Transcription Factors
PubMed: 32851773
DOI: 10.1002/ajmg.a.61823 -
Minerva Stomatologica Aug 2018Moebius syndrome is a rare condition characterized by bilateral facial and abducens nerve paralysis. The aim of this study is to evaluate the main orthodontic features... (Observational Study)
Observational Study
BACKGROUND
Moebius syndrome is a rare condition characterized by bilateral facial and abducens nerve paralysis. The aim of this study is to evaluate the main orthodontic features and the frequency of associated clinical characteristics in patients with Moebius syndrome (MS).
METHODS
According to Terzis classifications, 58 patients with MS aged 8 months to 46 years old underwent orthodontics and clinical examination.
RESULTS
Strabismus, upper and lower limb malformations, lip and palatal cleft were frequently associated with MS. Reduced TM movements were noted (48%). Cephalometric analysis did not allow identifying a typical facies and a characteristic cephalometric pattern; we have noticed a higher prevalence of Class II (56%) with micrognathia and excessive maxillary development probably due to the lack of lip seal. Early treatment is recommended, with a multidisciplinary approach to reduce the impact of sequelae on the lives of MS patients or their families.
CONCLUSIONS
Early treatment is recommended, with a multidisciplinary approach to diminish the impact of sequelae on the lives of MS patients or their families.
Topics: Adolescent; Adult; Cephalometry; Child; Child, Preschool; Cleft Lip; Cleft Palate; Diagnosis, Oral; Female; Humans; Infant; Limb Deformities, Congenital; Male; Malocclusion, Angle Class II; Micrognathism; Middle Aged; Mobius Syndrome; Orthodontics, Corrective; Patient Compliance; Phenotype; Strabismus; Young Adult
PubMed: 29527867
DOI: 10.23736/S0026-4970.18.04095-5 -
Nature Communications Dec 2022The cohesin complex participates in many structural and functional aspects of genome organization. Cohesin recruitment onto chromosomes requires nucleosome-free DNA and...
The cohesin complex participates in many structural and functional aspects of genome organization. Cohesin recruitment onto chromosomes requires nucleosome-free DNA and the Scc2-Scc4 cohesin loader complex that catalyzes topological cohesin loading. Additionally, the cohesin loader facilitates promoter nucleosome clearance in a yet unknown way, and it recognizes chromatin receptors such as the RSC chromatin remodeler. Here, we explore the cohesin loader-RSC interaction. Amongst multi-pronged contacts by Scc2 and Scc4, we find that Scc4 contacts a conserved patch on the RSC ATPase motor module. The cohesin loader directly stimulates in vitro nucleosome sliding by RSC, providing an explanation how it facilitates promoter nucleosome clearance. Furthermore, we observe cohesin loader interactions with a wide range of chromatin remodelers. Our results provide mechanistic insight into how the cohesin loader recognizes, as well as influences, the chromatin landscape, with implications for our understanding of human developmental disorders including Cornelia de Lange and Coffin-Siris syndromes.
Topics: Humans; Chromatin; Saccharomyces cerevisiae Proteins; Cell Cycle Proteins; Nucleosomes; Chromosome Segregation; Micrognathism
PubMed: 36509793
DOI: 10.1038/s41467-022-35444-6