scholarly journals Respiratory Distress in the Newborn with Primary Ciliary Dyskinesia

Children ◽  
2021 ◽  
Vol 8 (2) ◽  
pp. 153
Author(s):  
Evans Machogu ◽  
Benjamin Gaston
Keyword(s):  
Respiratory Distress ◽  
Primary Ciliary Dyskinesia ◽  
Chronic Otitis Media ◽  
Situs Inversus Totalis ◽  
Radiographic Findings ◽  
Neonatal Respiratory Distress ◽  
Organ Laterality ◽  
Wet Cough ◽  
Work Up ◽  
Ciliary Dyskinesia

Primary ciliary dyskinesia (PCD) is inherited in a predominantly autosomal recessive manner with over 45 currently identified causative genes. It is a clinically heterogeneous disorder that results in a chronic wet cough and drainage from the paranasal sinuses, chronic otitis media with hearing impairment as well as male infertility. Approximately 50% of patients have situs inversus totalis. Prior to the development of chronic oto-sino-pulmonary symptoms, neonatal respiratory distress occurs in more than 80% of patients as a result of impaired mucociliary clearance and mucus impaction causing atelectasis and lobar collapse. Diagnosis is often delayed due to overlapping symptoms with other causes of neonatal respiratory distress. A work up for PCD should be initiated in the newborn with compatible clinical features, especially those with respiratory distress, consistent radiographic findings or persistent oxygen requirement and/or organ laterality defects

scholarly journals Primary Ciliary Dyskinesia as a Cause of Neonatal Respiratory Distress: Implications for the Neonatologist

2003 ◽  
Vol 23 (8) ◽  
pp. 684-687 ◽  
Author(s):  
Tanzeema Hossain ◽  
Michael D Kappelman ◽  
Antonio R Perez-Atayde ◽  
Gregory J Young ◽  
Kenneth M Huttner ◽  
...  
Keyword(s):  
Respiratory Distress ◽  
Primary Ciliary Dyskinesia ◽  
Neonatal Respiratory Distress ◽  
Ciliary Dyskinesia

scholarly journals Late diagnosis of infants with PCD and neonatal respiratory distress

2020 ◽  
Author(s):  
Goutaki Myrofora ◽  
S Halbeisen Florian ◽  
Barbato Angelo ◽  
Crowley Suzanne ◽  
Harris Amanda ◽  
...  
Keyword(s):  
Respiratory Distress ◽  
Primary Ciliary Dyskinesia ◽  
List Type ◽  
Term Infants ◽  
Entire Cohort ◽  
Neonatal Respiratory Distress ◽  
Situs Solitus ◽  
History Of ◽  
Ciliary Dyskinesia ◽  
Laterality Defects

AbstractNeonatal respiratory distress (NRD) is common among infants with primary ciliary dyskinesia (PCD), but we do not know whether affected neonates are diagnosed timely.We used data from the international PCD cohort study (iPCD), including only participants diagnosed between 2000 and 2019 using current diagnostic criteria. We assessed the proportion of patients with PCD with a history of NRD and their age at diagnosis, stratifying by presence of laterality defects. First we analysed data from the entire cohort and then from a subgroup including children diagnosed using stricter criteria.Among the 1375 patients in the study, 45% had a history of NRD and 42% a laterality defect. Out of the 476 children with definite PCD diagnosis, 55% had a history of NRD and 50% a laterality defect. PCD was diagnosed at a median age of 3.4 years in this group, varying from less than 1 year in Norway and Cyprus to 10 years in Turkey. Overall, 30% of children with PCD were diagnosed during the first 12 months of life. This varied from 13% in those with situs solitus and no NRD, to 21% in those with situs solitus and NRD, 33% in those with situs anomalies but no NRD, and 52% in those with both NRD and situs anomalies.Our results suggest that we need to improve our knowledge of the neonatal presentation of infants with PCD, and apply this knowledge in neonatology so that these patients will receive appropriate care sooner, at the start of their extrauterine life.What is already known on this topic?Many patients with primary ciliary dyskinesia (PCD) present with neonatal respiratory distress (NRD).The neonatal period would therefore be an ideal window of opportunity to diagnose PCD early, before long-term damage to the lungs has occurred.Despite this, PCD is usually diagnosed late in life.What this study adds?55% of children with PCD in this large multinational dataset had a history of NRD.Among these, PCD was diagnosed early in those with laterality defects (median age 0.9 years) but late in those with situs solitus (5.9 years).This suggests that neonatologists and paediatricians do not suspect PCD as a cause of NRD in term infants unless it is accompanied by laterality defects.

scholarly journals Topological data analysis reveals genotype-phenotype relationships in primary ciliary dyskinesia

2021 ◽  
pp. 2002359
Author(s):  
Amelia Shoemark ◽  
Bruna Rubbo ◽  
Marie Legendre ◽  
Mahmood R. Fassad ◽  
Eric G. Haarman ◽  
...  
Keyword(s):  
Data Analysis ◽  
Respiratory Distress ◽  
Primary Ciliary Dyskinesia ◽  
Genetic Diagnosis ◽  
Case Series ◽  
Topological Data Analysis ◽  
National Study ◽  
Neonatal Respiratory Distress ◽  
Ciliary Dyskinesia ◽  
Topological Data

BackgroundPrimary ciliary dyskinesia (PCD) is a heterogeneous inherited disorder caused by mutations in approximately 50 cilia-related genes. PCD genotype-phenotype relationships have mostly arisen from small case series because existing statistical approaches to investigate relationships have been unsuitable for rare diseases.MethodsWe applied a topological data analysis (TDA) approach to investigate genotype-phenotype relationships in PCD. Data from separate training and validation cohorts included 396 genetically defined individuals carrying pathogenic variants in PCD genes. To develop the TDA models, twelve clinical and diagnostic variables were included. TDA-driven hypotheses were subsequently tested using traditional statistics.ResultsDisease severity at diagnosis measured by FEV1 z-score was (i) significantly worse in individuals with CCDC39 mutations compared to other gene mutations and (ii) better in those with DNAH11 mutations; the latter also reported less neonatal respiratory distress. Patients without neonatal respiratory distress had better preserved FEV1 at diagnosis. Individuals with DNAH5 mutations were phenotypically diverse. Cilia ultrastructure and beat pattern defects correlated closely to specific causative gene groups, confirming these tests can be used to support a genetic diagnosis.ConclusionsThis large scale multi-national study presents PCD as a syndrome with overlapping symptoms and variation in phenotype, according to genotype. TDA modelling confirmed genotype-phenotype relationships reported by smaller studies (e.g. FEV1 worse with CCDC39 mutations), and identified new relationships, including FEV1 preservation with DNAH11 mutations and diversity of severity with DNAH5 mutations.

scholarly journals Primary Ciliary Dyskinesia and Neonatal Respiratory Distress

PEDIATRICS ◽  
2014 ◽  
Vol 134 (6) ◽  
pp. 1160-1166 ◽  
Author(s):  
Tara Mullowney ◽  
David Manson ◽  
Raymond Kim ◽  
Derek Stephens ◽  
Vibhuti Shah ◽  
...  
Keyword(s):  
Respiratory Distress ◽  
Primary Ciliary Dyskinesia ◽  
Neonatal Respiratory Distress ◽  
Ciliary Dyskinesia

scholarly journals Late Diagnosis of Infants with PCD and Neonatal Respiratory Distress

2020 ◽  
Vol 9 (9) ◽  
pp. 2871
Author(s):  
Myrofora Goutaki ◽  
Florian S. Halbeisen ◽  
Angelo Barbato ◽  
Suzanne Crowley ◽  
Amanda Harris ◽  
...  
Keyword(s):  
Respiratory Distress ◽  
Primary Ciliary Dyskinesia ◽  
Late Diagnosis ◽  
Appropriate Care ◽  
Neonatal Respiratory Distress ◽  
Situs Solitus ◽  
History Of ◽  
Ciliary Dyskinesia ◽  
Laterality Defects ◽  
Neonatal Presentation

Neonatal respiratory distress (NRD) is common among infants with primary ciliary dyskinesia (PCD), but we do not know whether affected neonates receive a timely diagnosis. We used data from the international PCD cohort and assessed the proportion of patients with PCD who had a history of NRD and their age at diagnosis, stratifying by presence of laterality defects. First we analyzed data from all participants diagnosed after 2000, followed by individuals from a subgroup diagnosed using stricter criteria. Among the 1375 patients in the study, 45% had a history of NRD and 42% had laterality defects. Out of the 476 children with definite PCD diagnosis, 55% had a history of NRD and 50% had laterality defects. Overall, 30% of children with PCD were diagnosed during the first 12 months of life. This varied from 13% in those with situs solitus and no NRD, to 21% in those with situs solitus and NRD, 33% in those with situs anomalies but no NRD, and 52% in those with both situs anomalies and NRD. Our results suggest that we need to improve our knowledge of the neonatal presentation of infants with PCD and apply it so that these patients will receive appropriate care sooner.

scholarly journals Etiological Work-Up for Adults with Bronchiectasis: A Predictive Diagnostic Score for Primary Ciliary Dyskinesia and Cystic Fibrosis

2021 ◽  
Vol 10 (16) ◽  
pp. 3478
Author(s):  
Frederic Schlemmer ◽  
Agnes Hamzaoui ◽  
Sonia Zebachi ◽  
Aurelie Le Thuaut ◽  
Gilles Mangiapan ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Primary Ciliary Dyskinesia ◽  
Clinical Score ◽  
Adult Patients ◽  
Operating Characteristics ◽  
Diagnostic Score ◽  
Receiver Operating Characteristics Curve ◽  
Diagnostic Work ◽  
Work Up ◽  
Ciliary Dyskinesia

Background: etiological investigations are not done for all adult patients with bronchiectasis because of the availability and interpretation of tests. The aim of the study was to elaborate a score to identify patients at high risk of having cystic fibrosis or primary ciliary dyskinesia (CF/PCD), which require appropriate management. Methods: diagnostic work-ups were carried out on a French monocenter cohort, and results were subjected to logistic-regression analyses to identify the independent factors associated with CF/PCD diagnosis and, thereby, elaborate a score to validate in a second cohort. Results: among 188 patients, 158 had no obvious diagnosis and were enrolled in the algorithm-construction group. In multivariate analyses, age at symptom onset (8.69 (2.10–35.99); p = 0.003), chronic ENT symptoms or diagnosed sinusitis (10.53 (1.26–87.57); p = 0.03), digestive symptoms or situs inversus (5.10 (1.23–21.14); p = 0.025), and Pseudomonas. aeruginosa and/or Staphylococcus aureus isolated from sputum (11.13 (1.34–92.21); p = 0.02) are associated with CF or PCD. Receiver operating characteristics curve analysis, using a validation group of 167 patients with bronchiectasis, confirmed the score’s performance with AUC 0.92 (95% CI: 0.84–0.98). Conclusions: a clinical score may help identify adult patients with bronchiectasis at higher risk of having CF or PCD.

scholarly journals Emerging Genotype-Phenotype Relationships in Primary Ciliary Dyskinesia

2021 ◽  
Vol 22 (15) ◽  
pp. 8272
Author(s):  
Steven K Brennan ◽  
Thomas W Ferkol ◽  
Stephanie D Davis
Keyword(s):  
Primary Ciliary Dyskinesia ◽  
Pulmonary Infections ◽  
Disease Research ◽  
The Past ◽  
Clinical Presentations ◽  
Organ Laterality ◽  
Ciliary Dyskinesia ◽  
Laterality Defects ◽  
Severe Lung Disease ◽  
Severe Lung

Primary ciliary dyskinesia (PCD) is a rare inherited condition affecting motile cilia and leading to organ laterality defects, recurrent sino-pulmonary infections, bronchiectasis, and severe lung disease. Research over the past twenty years has revealed variability in clinical presentations, ranging from mild to more severe phenotypes. Genotype and phenotype relationships have emerged. The increasing availability of genetic panels for PCD continue to redefine these genotype-phenotype relationships and reveal milder forms of disease that had previously gone unrecognized.

Abstract 485: A Mouse Model of Primary Ciliary Dyskinesia Reveals High Frequencies of Heterotaxy and Complex Congenital Heart Defects

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Serena Y Tan ◽  
Linda Leatherbury ◽  
Julie Rosenthal ◽  
Xiao-Qing Zhao ◽  
Cecilia W Lo
Keyword(s):  
Situs Inversus ◽  
Primary Ciliary Dyskinesia ◽  
Congenital Heart ◽  
Heart Defects ◽  
Vena Cava ◽  
Situs Inversus Totalis ◽  
Complex Congenital Heart Disease ◽  
Ciliary Function ◽  
Situs Solitus ◽  
Ciliary Dyskinesia

Specification of left-right asymmetry is essential for formation of the four chamber heart and separate systemic and pulmonary circulation. Previous studies suggest monocilia at the embryonic node is required for left-right patterning. This patterning is perturbed in primary ciliary dyskinesia (PCD) where situs defects and bronchiectasis are observed, often due to ciliary dysfunction arising from dynein mutations. Most PCD patients exhibit situs solitus or situs inversus totalis, but heterotaxy with complex congenital heart disease (CHD) appears to be rare, reported as 6%. We recovered a mouse mutation in dynein Mdnah5 that disrupts ciliary function. Homozygote mutants exhibit situs phenotypes consistent with PCD in humans. To assess the frequency of CHD associated with PCD, we harvested16 litters of embryos. All wildtype and heterozygous offspring (89) showed normal body situs. Of the 21 (19%) homozygous mutants obtained, 6 had situs solitus, 7 situs inversus and 8 heterotaxy, with heterotaxy being any situs deviation in the cardiac, pulmonary or visceral anatomy. Of the heterotaxic embryos, 3 had levo and 5 dextrocardia. Histology and 3D reconstruction showed 7 of the heterotaxy embryos had complex CHD, which included atrial isomerism, superior-inferior ventricles (Figure ), malposition of the great arteries, AV cushion defects, and azygous continuation of the inferior vena cava. These results show a much higher frequency of heterotaxy and complex CHD than previously reported for PCD (38% vs. 6%), suggesting PCD patients should be screened for CHD. The high incidence of CHD associated with PCD indicates ciliary function may have other roles in cardiovascular patterning.

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