Laryngeal cleft: A literature review Martha, Vishnu V.; Vontela, Swetha; Calder, Alyssa N. ...
American journal of otolaryngology,
November-December 2021, 2021 Nov-Dec, 2021-11-00, 20211101, Volume:
42, Issue:
6
Journal Article
Peer reviewed
Laryngeal cleft is a congenital condition in which an opening in the posterior laryngotracheal wall allows food and liquid to pass from the esophageal lumen to the airway and causes aspiration. The ...severity of a laryngeal cleft is measured using the Benjamin-Inglis system, and can be managed conservatively or with a variety of surgical options With increased awareness, higher suspicion among primary physicians, advanced technology and improved intensive neonatal care services, more babies with laryngeal clefts survive in the modern era. Therefore, the focus has shifted from infant survival to treatment of laryngeal clefts and the challenging, complex medical conditions they create.
To understand current laryngeal cleft management and post-operative outcomes.
Literature review of laryngeal cleft studies from 2010 to 2021.
A total of 1033 patients were included. Based on 415 cases for whom sufficient classification data were available, the predominate symptom for patients with type I, III, and IV clefts is swallowing dysfunction, while the predominant symptoms for patients with type II clefts are stridor and aspiration. A wide variety of comorbidities involving several major organs has been reported with laryngeal clefts, which tend to impact clinical outcomes negatively. Approximately 19% of type I clefts have been treated conservatively successfully, but the majority was treated surgically. Most studies that used injection laryngoplasty for type I clefts reported highly successful repairs without complications or delays in additional procedures. Ninety-eight percent all type II clefts were treated with endoscopic repair; 87% of patients with type III clefts received endoscopic repair; and 66% of patients with type IV clefts underwent open surgery. Approximately 62% of resolved cases were reported within 12 months, while 50.87% of failed cases were reported within 6 weeks.
There are multiple treatment approaches, each of which may be applicable depending on factors such as laryngeal cleft type, severity of presentation, and comorbidities. Conservative approaches appear to be most useful for type I clefts or in patients with mild symptoms, while surgical management can be considered for any type of laryngeal cleft. The benefit of injection laryngoplasty, endoscopic repair and open surgery can also vary, but injection laryngoplasty and endoscopic repair are used most commonly. Open surgery should be to be considered if patients present with severe cleft types or if it is unsafe to perform other surgical techniques. Familiarity with this literature review should help clinicians understand clinical characteristics, direct medical management, and guide successful resolution of laryngeal clefts.
Chromosomal microarray (CMA) is recommended as the first-tier test in evaluation of individuals with neurodevelopmental disability and congenital anomalies. CMA may not detect balanced cytogenomic ...abnormalities or uniparental disomy (UPD), and deletion/duplications and regions of homozygosity may require additional testing to clarify the mechanism and inform accurate counseling. We conducted an evidence review to synthesize data regarding the benefit of additional testing after CMA to inform a genetic diagnosis.
The review was guided by key questions related to the detection of genomic events that may require additional testing. A PubMed search for original research articles, systematic reviews, and meta-analyses was evaluated from articles published between 1 January 1983 and 31 March 2017. Based on the key questions, articles were retrieved and data extracted in parallel with comparison of results and discussion to resolve discrepancies. Variables assessed included study design and outcomes.
A narrative synthesis was created for each question to describe the occurrence of, and clinical significance of, additional diagnostic findings from subsequent testing performed after CMA.
These findings may be used to assist the laboratory and clinician when making recommendations about additional testing after CMA, as it impacts clinical care, counseling, and diagnosis.
EUROCAT (European Surveillance of Congenital Anomalies) is the network of population-based registers of congenital anomaly in Europe, with a common protocol and data quality review, covering 1.5 ...million annual births in 22 countries. EUROCAT recorded a total prevalence of major congenital anomalies of 23.9 per 1,000 births for 2003-2007. 80% were livebirths. 2.5% of livebirths with congenital anomaly died in the first week of life. 2.0% were stillbirths or fetal deaths from 20 weeks gestation. 17.6% of all cases were terminations of pregnancy following prenatal diagnosis (TOPFA). Thus, congenital anomalies overwhelmingly concern children surviving the early neonatal period, who have important medical, social or educational needs. The prevalence of chromosomal anomalies was 3.6 per 1,000 births, contributing 28% of stillbirths/fetal deaths from 20 weeks gestation with congenital anomaly, and 48% of all TOPFA. Congenital heart defects (CHD) were the most common non-chromosomal subgroup, at 6.5 per 1,000 births, followed by limb defects (3.8 per 1,000), anomalies of urinary system (3.1 per 1,000) and nervous system defects (2.3 per 1,000). In 2004, perinatal mortality associated with congenital anomaly was 0.93 per 1,000 births, and TOPFA 4.4 per 1,000 births, with considerable country variation. Primary prevention of congenital anomalies in the population based on controlling environmental risk factors is a crucial policy priority, including preconceptional care and whole population approaches.
Abstract
Congenital vertebral malformations (CVMs) are associated with human TBX6 compound inheritance that combines a rare null allele and a common hypomorphic allele at the TBX6 locus. Our previous ...in vitro evidence suggested that this compound inheritance resulted in a TBX6 gene dosage of less than haploinsufficiency (i.e. <50%) as a potential mechanism of TBX6-associated CVMs. To further investigate this pathogenetic model, we ascertained and collected 108 Chinese CVM cases and found that 10 (9.3%) of them carried TBX6 null mutations in combination with common hypomorphic variants at the second TBX6 allele. For in vivo functional verification and genetic analysis of TBX6 compound inheritance, we generated both null and hypomorphic mutations in mouse Tbx6 using the CRISPR-Cas9 method. These Tbx6 mutants are not identical to the patient variants at the DNA sequence level, but instead functionally mimic disease-associated TBX6 variants. Intriguingly, as anticipated by the compound inheritance model, a high penetrance of CVM phenotype was only observed in the mice with combined null and hypomorphic alleles of Tbx6. These findings are consistent with our experimental observations in humans and supported the dosage effect of TBX6 in CVM etiology. In conclusion, our findings in the newly collected human CVM subjects and Tbx6 mouse models consistently support the contention that TBX6 compound inheritance causes CVMs, potentially via a gene dosage-dependent mechanism. Furthermore, mouse Tbx6 mutants mimicking human CVM-associated variants will be useful models for further mechanistic investigations of CVM pathogenesis in the cases associated with TBX6.
Aims/hypothesis
Pre-existing diabetes is associated with an increased risk of stillbirth, but few studies have excluded the effect of congenital anomalies. This study used data from a long-standing ...population-based survey of women with pre-existing diabetes to investigate the risks of fetal and infant death and quantify the contribution of glycaemic control.
Methods
All normally formed singleton offspring of women with pre-existing diabetes (1,206 with type 1 diabetes and 342 with type 2 diabetes) in the North of England during 1996–2008 were identified from the Northern Diabetes in Pregnancy Survey. RRs of fetal death (≥20 weeks of gestation) and infant death were estimated by comparison with population data from the Northern Perinatal Morbidity and Mortality Survey. Predictors of fetal and infant death in women with pre-existing diabetes were examined by logistic regression.
Results
The prevalence of fetal death in women with diabetes was over four times greater than in those without (RR 4.56 95% CI 3.42, 6.07,
p
< 0.0001), and for infant death it was nearly doubled (RR 1.86 95% CI 1.00, 3.46,
p
= 0.046). There was no difference in the prevalence of fetal death (
p
= 0.51) or infant death (
p
= 0.70) between women with type 1 diabetes and women with type 2 diabetes. There was no evidence that the RR of fetal and infant death had changed over time (
p
= 0.95). Increasing periconception HbA
1c
concentration above 49 mmol/mol (6.6%) (adjusted odds ratio aOR 1.02 95% CI 1.00, 1.04,
p
= 0.01), prepregnancy retinopathy (aOR 2.05 95% CI 1.04, 4.05,
p
= 0.04) and lack of prepregnancy folic acid consumption (aOR 2.52 95% CI 1.12, 5.65,
p
= 0.03) were all independently associated with increased odds of fetal and infant death.
Conclusions/interpretation
Pre-existing diabetes is associated with a substantially increased risk of fetal and infant death in normally formed offspring, the effect of which is largely moderated by glycaemic control.
Gene regulatory networks, in which differential expression of regulator genes induce differential expression of their target genes, underlie diverse biological processes such as embryonic ...development, organ formation and disease pathogenesis. An archetypical systems biology approach to mapping these networks involves the combined application of (1) high-throughput sequencing-based transcriptome profiling (RNA-seq) of biopsies under diverse network perturbations and (2) network inference based on gene–gene expression correlation analysis. The comparative analysis of such correlation networks across cell types or states, differential correlation network analysis, can identify specific molecular signatures and functional modules that underlie the state transition or have context-specific function. Here, we review the basic concepts of network biology and correlation network inference, and the prevailing methods for differential analysis of correlation networks. We discuss applications of gene expression network analysis in the context of embryonic development, cancer, and congenital diseases.
Objective
This study aimed to describe the clinical features, associated extragenital anomalies, and management of Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome in a Thai population.
Methods
This ...retrospective study analyzed the medical records of 96 patients with MRKH syndrome diagnosed and treated at a university hospital and tertiary referral center in southern Thailand between 2000 and 2022.
Results
The study included 96 patients with MRKH syndrome. The most common symptom was primary amenorrhea (88.5%), followed by difficulty or inability to engage in sexual intercourse (9.4%) and pelvic mass (2.1%). Notably, 80.3% of the patients did not have extragenital malformations and were diagnosed with MRKH type I (typical form), whereas 19.7% were categorized as MRKH type II (atypical form). Skeletal malformations were the most frequent extragenital anomalies and were present in 19.5% of patients, with scoliosis being the most common skeletal condition. Other extragenital malformations included renal (8.5%) and neurological (1.0%) abnormalities. Clinical vaginal examination revealed complete atresia in 21.8% and vaginal hypoplasia (median vaginal length, 3 cm) in 78.2% of the patients. Half of the patients did not receive treatment because they had not engaged in sexual intercourse. In this cohort, 41.7% of the patients had no difficulty performing sexual intercourse. Hence, self-dilation therapy or concomitant dilation was recommended. Only eight patients (8.3%) underwent surgical reconstruction of the vagina.
Conclusion
This study confirmed the complexity and heterogeneity of the phenotypic manifestations of MRKH, including the degree of vaginal atresia and types and rates of associated malformations.
Many human teratogens are associated with a spectrum of congenital anomalies rather than a single defect, and therefore the identification of congenital anomalies occurring together more frequently ...than expected may improve the detection of teratogens. Thirty-two EUROCAT congenital anomaly registries covering 6,599,765 births provided 123,566 cases with one or more major congenital anomalies (excluding chromosomal and genetic syndromes) for the birth years 2008-2016. The EUROCAT multiple congenital anomaly algorithm identified 8804 cases with two or more major congenital anomalies in different organ systems, that were not recognized as part of a syndrome or sequence. For each pair of anomalies, the odds of a case having both anomalies relative to having only one anomaly was calculated and the p value was estimated using a two-sided Fisher's exact test. The Benjamini-Hochberg procedure adjusted p values to control the false discovery rate and pairs of anomalies with adjusted p values < 0.05 were identified. A total of 1386 combinations of two anomalies were analyzed. Out of the 31 statistically significant positive associations identified, 20 were found to be known associations or sequences already described in the literature and 11 were considered "potential new associations" by the EUROCAT Coding and Classification Committee. After a review of the literature and a detailed examination of the individual cases with the anomaly pairs, six pairs remained classified as new associations. In summary, systematically searching for congenital anomalies occurring together more frequently than expected using the EUROCAT database is worthwhile and has identified six new associations that merit further investigation.