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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 -
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 -
Molecular Genetics & Genomic Medicine Nov 2023BICRA, a transcript regulator, was identified as the genetic factor of Coffin-Siris syndrome 12 (CSS12) recently, which was characterized by diverse neurodevelopmental...
BACKGROUND
BICRA, a transcript regulator, was identified as the genetic factor of Coffin-Siris syndrome 12 (CSS12) recently, which was characterized by diverse neurodevelopmental delays. Up to now, limited studies of BICRA in neurodevelopmental delay have been reported.
METHODS
Clinical data such as EEGs, MRIs, routine blood, and physical examination were collected. Trio whole exome sequencing (WES) of the family was performed, and all variants with a minor allele frequency (<0.01) in exon and canonical splicing sites were selected for further pathogenic evaluation. Candidate variants were validated by Sanger sequencing. The BICRA-related literature was reviewed and the clinical characteristics were summarized.
RESULTS
We reported a CSS12 proband with a narrow and slightly clinical phenotype who only exhibited language developmental delay, hypotonia, and slight gastrointestinal features. WES revealed a de novo variant in exon 6 of BICRA [NM_015711.3: c.1666C>T, p.Gln556*]. This variant resulted in an early translation termination at 556th of BICRA, not collected in the public population database (gnomAD), and classified as pathogenic according to the ACMG guideline.
CONCLUSION
Our results expanded the pathogenic genetic and clinical spectrum of BICRA-related diseases.
Topics: Humans; Transcription Factors; Intellectual Disability; Abnormalities, Multiple; Micrognathism
PubMed: 37485815
DOI: 10.1002/mgg3.2250 -
The Laryngoscope Apr 2021Detection of fetal airway compromise through imaging raises the possible need for ex utero intrapartum treatment (EXIT) procedures. Despite EXIT procedures involving...
OBJECTIVE
Detection of fetal airway compromise through imaging raises the possible need for ex utero intrapartum treatment (EXIT) procedures. Despite EXIT procedures involving massive resource utilization and posing increased risk to the mother, decisions for EXIT are usually based on anecdotal experience. Our objectives were to analyze prenatal consultations with potential fetal airway obstruction for imaging and obstetric findings used to determine management strategy.
METHODS
Retrospective chart review was performed for prenatal abnormal fetal airway consults between 2004-2019 at a quaternary pediatric facility. Data collected included demographics, imaging characteristics, delivery information, and airway management. Our primary outcome was EXIT performance and the secondary outcome was postnatal airway management. Fisher's exact test was used to compare management decisions, outcomes, and imaging findings.
RESULTS
Thirty-seven patients met inclusion criteria. The most common diagnoses observed were lymphatic malformation, teratoma, and micrognathia. Of the imaging findings collected, only midline neck mass location was associated with EXIT procedure performance. Factors associated with invasive airway support at birth were mass-induced in-utero neck extension and neck vessel compression, polyhydramnios, and micrognathia.
CONCLUSIONS
Multidisciplinary input and interpretation of prenatal imaging can guide management of fetal airway-related pathology. EXIT is an overall safe procedure and can decrease risk due to airway obstruction at birth. We identified in-utero neck extension, neck vessel compression, micrognathia, and polyhydramnios as better indicators of a need for invasive airways measures at birth and suggest use of these criteria in combination with clinical judgement when recommending EXIT.
LEVEL OF EVIDENCE
4 Laryngoscope, 131:E1357-E1362, 2021.
Topics: Adult; Airway Management; Airway Obstruction; Cesarean Section; Female; Fetal Diseases; Gestational Age; Humans; Lymphatic Abnormalities; Male; Micrognathism; Neck; Pregnancy; Retrospective Studies; Teratoma; Ultrasonography, Prenatal
PubMed: 32770766
DOI: 10.1002/lary.28959 -
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 -
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 -
Journal of Clinical Sleep Medicine :... Jul 2022Craniofacial malformations with micrognathia cause high grades of obstructive sleep apnea (OSA) measured by polysomnography (PSG). Mandibular distraction osteogenesis is...
STUDY OBJECTIVES
Craniofacial malformations with micrognathia cause high grades of obstructive sleep apnea (OSA) measured by polysomnography (PSG). Mandibular distraction osteogenesis is a novel procedure for upper airway obstruction relief. Our primary objective was to describe the utilization of PSGs to improve obstruction in patients undergoing mandibular distraction.
METHODS
This is a retrospective study. Patients with micrognathia and severe upper airway obstruction, presenting with severe OSA diagnosed by PSG, were included from a single tertiary care center between 2015 and 2019. PSGs were done (1) prior to surgery, (2) once the cosmetic goal was achieved (Post-Op 1), and (3) if residual moderate-to-severe OSA was seen, every 2 nights until mild or no OSA was achieved (Post-Op 2).
RESULTS
Thirteen patients were included. The median age at surgery was 1.1 months (10 days-3 months). All 13 patients had baseline severe OSA, with a median obstructive apnea-hypopnea index of 33 events/h and a median O nadir of 73%. Post-Op 1 PSG was done at a median of 6 days after surgery. Median first postoperative obstructive apnea-hypopnea index in all 13 patients was 6.8 events/h, with a median O nadir of 87%. A median additional distraction of 3 mm was needed beyond the traditionally recommended advancement. Long-term follow-up studies at or after 1 year were done in 5 patients, all showing persistent nonsevere OSA.
CONCLUSIONS
This is the first case series utilizing PSGs as a guide for mandibular distraction osteogenesis in patients with micrognathia showing the need for jaw overcorrection to achieve resolution of OSA.
CITATION
Kochhar R, Modi V, de Silva N, et al. Polysomnography-guided mandibular distraction osteogenesis in Pierre Robin sequence patients. . 2022;18(7):1749-1755.
Topics: Airway Obstruction; Humans; Infant; Mandible; Micrognathism; Osteogenesis, Distraction; Pierre Robin Syndrome; Polysomnography; Retrospective Studies; Sleep Apnea, Obstructive; Treatment Outcome
PubMed: 35332870
DOI: 10.5664/jcsm.9960 -
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