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Laryngoscope Investigative... Apr 2018Describe the factors that exacerbate upper airway obstructions (UAOs) in neonates.
OBJECTIVE
Describe the factors that exacerbate upper airway obstructions (UAOs) in neonates.
STUDY DESIGN
Retrospective chart review.
SETTING
Pediatric tertiary care hospital.
SUBJECTS AND METHODS
All neonates hospitalized between 1/1/2010 and 12/31/2014 diagnosed with either: 1) laryngomalacia, 2) Pierre Robin sequence, or 3) vocal cord paralysis were included in this study. Patient charts were reviewed to determine factors that exacerbated symptoms of airway obstruction. The independent variable was patient diagnosis, and the outcome measure was exacerbating factors.
RESULTS
In patients with laryngomalacia (n = 31), 41.9% worsened with agitation, 38.7% worsened with feeding, 16.1% worsened with positioning, 0.0% worsened during sleep, and 25.8% had no aggravating factors. In Pierre-Robin patients (n = 31), 48.4% worsened with agitation, 16.1% worsened with feeding, 61.3% worsened with positional changes, 0.0% worsened during sleep, and 12.9% had no aggravating factors. In vocal cord paralysis patients (n = 25), 72.0% worsened with agitation, 8.0% worsened with feeding, 20.0% worsened with positional changes, 4.0% worsened during sleep, and 24.0% had no aggravating factors.
CONCLUSION
Airway obstruction was not reliably exacerbated during sleep for any of the diagnoses studied in this review. Our findings show that agitation exacerbates airway obstruction in most patients with vocal cord paralysis, and positioning exacerbates airway obstruction in the majority of patients with PRS. Aggravating factors in laryngomalacia are variable. These findings question the utility of polysomnography as a diagnostic tool for hospitalized neonates with these conditions.
LEVEL OF EVIDENCE
4.
PubMed: 29721538
DOI: 10.1002/lio2.137 -
Familial Cancer Oct 2023Pathogenic germline DICER1 variants are associated with pleuropulmonary blastoma, multinodular goiter, embryonal rhabdomyosarcoma and other tumour types, while mosaic...
Pathogenic germline DICER1 variants are associated with pleuropulmonary blastoma, multinodular goiter, embryonal rhabdomyosarcoma and other tumour types, while mosaic missense DICER1 variants in the RNase IIIb domain are linked to cause GLOW (global developmental delay, lung cysts, overgrowth, and Wilms' tumor) syndrome. Here, we report four families with germline DICER1 pathogenic variants in which one member in each family had a more complex phenotype, including skeletal findings, facial dysmorphism and developmental abnormalities. The developmental features occur with a variable expressivity and incomplete penetrance as also described for the neoplastic and dysplastic lesions associated with DICER1 variants. Whole exome sequencing (WES) was performed on all four cases and revealed no further pathogenic or likely pathogenic dominant, homozygous or compound heterozygous variants in three of them. Notably, a frameshift variant in ARID1B was detected in one patient explaining part of her phenotype. This series of patients shows that pathogenic DICER1 variants may be associated with a broader phenotypic spectrum than initially assumed, including predisposition to different tumours, skeletal findings, dysmorphism and developmental abnormalities, but genetic work up in syndromic patients should be comprehensive in order not to miss additional underlying /modifying causes.
Topics: Female; Humans; Germ-Line Mutation; Phenotype; Frameshift Mutation; Cysts; Ribonuclease III; Germ Cells; DEAD-box RNA Helicases
PubMed: 34331184
DOI: 10.1007/s10689-021-00271-z -
Frontiers in Cell and Developmental... 2024The pivotal role of FGF18 in the regulation of craniofacial and skeletal development has been well established. Previous studies have demonstrated that mice with...
The pivotal role of FGF18 in the regulation of craniofacial and skeletal development has been well established. Previous studies have demonstrated that mice with deficiency in exhibit severe craniofacial dysplasia. Recent clinical reports have revealed that the duplication of chromosome 5q32-35.3, which encompasses the gene, can lead to cranial bone dysplasia and congenital craniosynostosis, implicating the consequence of possible overdosed FGF18 signaling. This study aimed to test the effects of augmented FGF18 signaling by specifically overexpressing the gene in cranial neural crest cells using the mouse model. The results showed that overexpression of leads to craniofacial abnormalities in mice similar to the Pierre Robin sequence in humans, including abnormal tongue morphology, micrognathia, and cleft palate. Further examination revealed that elevated levels of activated the Akt and Erk signaling pathways, leading to an increase in the proliferation level of tongue tendon cells and alterations in the contraction pattern of the genioglossus muscle. Additionally, we observed that excessive FGF18 signaling contributed to the reduction in the length of Meckel's cartilage and disrupted the development of condylar cartilage, ultimately resulting in mandibular defects. These anomalies involve changes in several downstream signals, including Runx2, p21, Akt, Erk, p38, Wnt, and Ihh. This study highlights the crucial role of maintaining the balance of endogenous FGF18 signaling for proper craniofacial development and offers insights into potential formation mechanisms of the Pierre Robin sequence.
PubMed: 38694818
DOI: 10.3389/fcell.2024.1376814 -
Journal of Anaesthesiology, Clinical... 2023
PubMed: 38025574
DOI: 10.4103/joacp.joacp_435_21 -
The Cleft Palate-craniofacial Journal :... Nov 2023Prior research suggests that children with cleft palate (CP) are at increased risk of obstructive sleep-disordered breathing (SDB). However, few studies differentiate...
OBJECTIVE
Prior research suggests that children with cleft palate (CP) are at increased risk of obstructive sleep-disordered breathing (SDB). However, few studies differentiate the effects of CP repair on SDB based on syndrome status. The goal of this study was to evaluate differences in SDB after palatoplasty among children with nonsyndromic CP, syndromic CP, and isolated Robin sequence (RS).
DESIGN
Retrospective chart review.
SETTING
Tertiary academic children's hospital.
PATIENTS/PARTICIPANTS
A total of 145 children who underwent primary CP repair from 2014 to 2021.
MAIN OUTCOME MEASURE
Post-palatoplasty SDB is defined as parent-reported symptoms and/or evidence of obstructive sleep apnea (OSA).
RESULTS
Median age at palatoplasty was 11.1 [IQR 10.2-13.6] months. Most patients (61.4%) had nonsyndromic CP, 26.9% had a syndrome, and 11.7% had RS. Children with syndromic CP and RS had more post-palatoplasty SDB symptoms (56.4% vs 58.8% vs 30.3%, = .006) and higher rates of OSA (25.6% vs 29.4% vs 5.6%, = .001) compared to children with nonsyndromic CP after palatoplasty. Children with syndromic CP and RS had nearly 3 to 4 higher odds of post-palatoplasty SDB than children with nonsyndromic CP (adjusted odds ratio [aOR] 2.88, 95% CI 1.29-6.47, = .010; aOR 3.73, 95% CI 1.19-11.70, = .024).
CONCLUSION
This study showed that children with CP experience higher rates of SDB after palatoplasty than the general pediatric population. Within the cohort, children with syndromic CP and isolated RS were more likely to have obstructive sleep disorders than nonsyndromic children after palatoplasty. Clinicians should counsel caregivers accordingly and closely monitor these groups for SDB after palate repair.
Topics: Child; Humans; Infant; Cleft Palate; Retrospective Studies; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Pierre Robin Syndrome
PubMed: 35642260
DOI: 10.1177/10556656221105203 -
Genetics in Medicine : Official Journal... Aug 2020Genitopatellar syndrome and Say-Barber-Biesecker-Young-Simpson syndrome are caused by variants in the KAT6B gene and are part of a broad clinical spectrum called KAT6B... (Review)
Review
PURPOSE
Genitopatellar syndrome and Say-Barber-Biesecker-Young-Simpson syndrome are caused by variants in the KAT6B gene and are part of a broad clinical spectrum called KAT6B disorders, whose variable expressivity is increasingly being recognized.
METHODS
We herein present the phenotypes of 32 previously unreported individuals with a molecularly confirmed diagnosis of a KAT6B disorder, report 24 new pathogenic KAT6B variants, and review phenotypic information available on all published individuals with this condition. We also suggest a classification of clinical subtypes within the KAT6B disorder spectrum.
RESULTS
We demonstrate that cerebral anomalies, optic nerve hypoplasia, neurobehavioral difficulties, and distal limb anomalies other than long thumbs and great toes, such as polydactyly, are more frequently observed than initially reported. Intestinal malrotation and its serious consequences can be present in affected individuals. Additionally, we identified four children with Pierre Robin sequence, four individuals who had increased nuchal translucency/cystic hygroma prenatally, and two fetuses with severe renal anomalies leading to renal failure. We also report an individual in which a pathogenic variant was inherited from a mildly affected parent.
CONCLUSION
Our work provides a comprehensive review and expansion of the genotypic and phenotypic spectrum of KAT6B disorders that will assist clinicians in the assessment, counseling, and management of affected individuals.
Topics: Blepharophimosis; Exons; Histone Acetyltransferases; Humans; Intellectual Disability; Mutation
PubMed: 32424177
DOI: 10.1038/s41436-020-0811-8 -
Plastic and Reconstructive Surgery.... May 2018Pierre Robin sequence (PRS)-related airway obstruction is often treated surgically; however, objective measures predicting the need for surgery are poorly defined.
BACKGROUND
Pierre Robin sequence (PRS)-related airway obstruction is often treated surgically; however, objective measures predicting the need for surgery are poorly defined.
METHODS
A retrospective chart review was performed on 171 neonates with PRS. Infants were grouped based upon intervention modality: nonsurgical (conservative) or surgical [mandibular distraction osteogenesis (MDO) or tracheostomy]. Demographic data, physical examination findings, and study results were compared between groups to determine risk factors for surgical intervention, and to predict long-term success or failure of those interventions.
RESULTS
The most significant, objective risk factor among those receiving surgery was a poor preintervention sleep study [obstructive index (OI): 42.4 versus 12.9 for the conservative treatment group; < 0.001]. Only 11% of those treated conservatively had an OI >20, whereas 67.5% of those treated surgically met this severity measure. Of those receiving surgery, tracheostomy was associated with neurologic impairment ( = 0.030) and low birth weight ( = 0.046) compared with the MDO group. Together with syndromic status, these risk factors were useful for predicting failure of MDO to avoid subsequent tracheostomy (test sensitivity and specificity were 64.2% and 100.0%, respectively). No long-term differences in speech or micrognathia were detected between the 3 groups; however, those treated conservatively or with MDO had improved long-term feeding and airway obstruction outcomes compared with the tracheostomy group.
CONCLUSIONS
Surgical intervention for PRS-related tongue-based airway obstruction should be strongly considered with an OI >20. Tracheostomy should be reserved for complex patients with concomitant syndromic diagnosis, neurologic impairment, and low birth weight.
PubMed: 29922540
DOI: 10.1097/GOX.0000000000001688 -
Frontiers in Pediatrics 2018Pierre Robin sequence (PRS) may lead to life-threatening respiratory and feeding disorders. With the aim to analyse the association of the severities of retrognathia and...
Pierre Robin sequence (PRS) may lead to life-threatening respiratory and feeding disorders. With the aim to analyse the association of the severities of retrognathia and glossoptosis with those of respiratory and feeding disorders, we retrospectively studied a series of 50 infants with retrognathia, glossoptosis, cleft palate, and airway obstruction. The patients were managed from birth to at least 6 years of age by a single pediatric team at the Armand Trousseau Hospital in Paris within a 12 years period (2000-2012). Retrognathia and glossoptosis were graded in the neonatal period according to a specific clinical examination. Ventilation assistance was required for 32/50 (64%) patients, and enteral feeding for 41/50 (82%). The grades of retrognathia and glossoptosis and the severity of respiratory disorders did not differ between patients with isolated PRS and syndromic PRS. Severe respiratory disorders were more common and long-lasting feeding (>12 months) was more frequently required in patients with syndromic PRS compared with isolated PRS (42 vs. 13%, = 0.04 and 42 vs. 4%, < 0.01 respectively). Using univariate analysis, neurological impairments and laryngomalacia were associated with severe respiratory disorders [Odds ratio (OR) 5.0, 95% CI 1.3-19.6; and OR 14.6, 95% CI 1.3-161.4; < 0.05] as well as with long-lasting feeding (>12 months) disorders (OR 18.6, 95% CI 3.9-89.2 and OR 20.4, 95% CI 3,4-122.8; < 10). Syndromic SPR status was also associated with severe respiratory disorders (OR 4.9, 95% CI 1-32.5; < 0.05). Using multivariate analysis, only syndromic PRS status was predictive for severe respiratory disorders (adjusted OR 8, 95% CI 1.47-44.57; < 0.05); and only neurological impairments remained a significant risk for long lasting feeding disorders (>12 months) (adjusted OR 21.72, 95% CI 3.4-138.63; < 10). The grades of retrognathia and glossoptosis were not predictive factors for the severity of respiratory and feeding disorders. : In children with PRS, the severity of clinical conditions may not correlate with anatomic variables but rather with laryngeal abnormalities, neurological impairement and syndromic PRS status.
PubMed: 30525013
DOI: 10.3389/fped.2018.00351 -
Canadian Respiratory Journal 2015
Topics: Airway Management; Airway Obstruction; Female; Humans; Infant, Premature, Diseases; Male; Pierre Robin Syndrome
PubMed: 26057370
DOI: 10.1155/2015/959686 -
Annals of Maxillofacial Surgery 2016The disorder currently accepted as Pierre Robin syndrome/anomaly/sequence (PRS) has been plagued by controversy ever since initially being described. Controversy exists...
CONTEXT
The disorder currently accepted as Pierre Robin syndrome/anomaly/sequence (PRS) has been plagued by controversy ever since initially being described. Controversy exists not only about the appropriate terminology and etiopathogenesis of the disorder but also about its management. Clinical findings and treatment outcomes of a large database of 266 PRS cases were compared with the current state of knowledge in the scientific literature, relating to history, clinical description, diagnostic criteria, epidemiology, theories of oligohydramnios, mandibular catch-up growth, midfacial hyperplasia, and the early management.
AIMS OF PART 2
Contribute to the sparse scientific knowledge about pathogenesis and involved genetics.
SUBJECTS AND METHODS
An analysis of this large database was conducted focusing on genetic involvement, family history, and the incidence of additional syndromes.
RESULTS
Beside of differences related to clinical signs of dyspnea, feeding problems and mortality rates, various concomitant syndromes, and genetic abnormalities were found in cases of Fairbairn-Robin triad (FRT) and Siebold-Robin sequence (SRS), in addition to differences in relation to clinical signs of dyspnea, feeding problems, and mortality rates.
CONCLUSION
Multiple FRT cases presented with various concomitant syndromes and genetic abnormalities, but only one type occurred in two SRS cases. The latter presented a significantly different mortality rate when compared to the FRT subgroup.
PubMed: 27563604
DOI: 10.4103/2231-0746.186134