Rhinosinusitis in Pediatric Primary Ciliary Dyskinesia: Impact of Disease

2019 ◽  
Vol 161 (5) ◽  
pp. 877-880 ◽  
Author(s):  
Jay M. Bhatt ◽  
Ethan G. Muhonen ◽  
Maxene Meier ◽  
Scott D. Sagel ◽  
Kenny H. Chan
Keyword(s):  
Primary Ciliary Dyskinesia ◽  
Genetic Disorder ◽  
Retrospective Chart Review ◽  
Sinus Surgery ◽  
Record System ◽  
Sinus Disease ◽  
Respiratory Cilia ◽  
Genetic Test Results ◽  
Biallelic Mutations ◽  
Ciliary Dyskinesia

Objectives Primary ciliary dyskinesia (PCD) is a genetic disorder characterized by abnormal respiratory cilia ultrastructure and/or function causing defective mucociliary clearance. We investigated the extent and severity of rhinosinusitis in a large cohort of children with PCD and explored associations among risk factors, including genotype and sinus disease. Study Design Retrospective chart review. Setting Tertiary academic children’s hospital. Subjects and Methods A review was conducted with a patient registry at the PCD Foundation Center at our institution. Demographic, imaging, clinical, and operative data were reviewed through the institutional electronic health record system. Results Fifty-four subjects were identified with mean and median age at diagnosis of 5.2 and 4.0 years. The male:female ratio was 35%:65%. Sinus symptoms were present in 46 (85%) subjects, 22 of whom had chronic rhinosinusitis. Nineteen (35%) subjects underwent operative intervention, consisting of endoscopic sinus surgery (ESS; 16 patients) and maxillary lavage (3 patients). Nineteen subjects underwent adenoidectomy for PCD-related indications. Five sinus-related admissions in 3 subjects were noted during the study period, and no complication of rhinosinusitis occurred in the cohort. Genetic test results were available in 27 subjects, in whom 23 (85%) had biallelic mutations in a PCD gene. Demographic factors, Lund-Mackay score, and PCD genotype were not found to be predictors for ESS or hospitalization in our cohort. Conclusion While rhinosinusitis was common in our PCD cohort, most patients did not require ESS. Since complications of rhinosinusitis were uncommon, we recommend judicious surgical management tailored to the patient’s symptoms.

scholarly journals Deep phenotyping, including quantitative ciliary beating parameters, and extensive genotyping in primary ciliary dyskinesia

2019 ◽  
Vol 57 (4) ◽  
pp. 237-244 ◽  
Author(s):  
Sylvain Blanchon ◽  
Marie Legendre ◽  
Mathieu Bottier ◽  
Aline Tamalet ◽  
Guy Montantin ◽  
...  
Keyword(s):  
Primary Ciliary Dyskinesia ◽  
High Speed ◽  
Genetic Disorder ◽  
Beat Frequency ◽  
Ciliary Beat Frequency ◽  
Central Complex ◽  
Ciliary Beating ◽  
Recovery Stroke ◽  
Biallelic Mutations ◽  
Ciliary Dyskinesia

BackgroundPrimary ciliary dyskinesia (PCD) is a rare genetic disorder resulting in abnormal ciliary motility/structure, extremely heterogeneous at genetic and ultrastructural levels. We aimed, in light of extensive genotyping, to identify specific and quantitative ciliary beating anomalies, according to the ultrastructural phenotype.MethodsWe prospectively included 75 patients with PCD exhibiting the main five ultrastructural phenotypes (n=15/group), screened all corresponding PCD genes and measured quantitative beating parameters by high-speed video-microscopy (HSV).ResultsSixty-eight (91%) patients carried biallelic mutations. Combined outer/inner dynein arms (ODA/IDA) defect induces total ciliary immotility, regardless of the gene involved. ODA defect induces a residual beating with dramatically low ciliary beat frequency (CBF) related to increased recovery stroke and pause durations, especially in case of DNAI1 mutations. IDA defect with microtubular disorganisation induces a low percentage of beating cilia with decreased beating angle and, in case of CCDC39 mutations, a relatively conserved mean CBF with a high maximal CBF. Central complex defect induces nearly normal beating parameters, regardless of the gene involved, and a gyrating motion in a minority of ciliated edges, especially in case of RSPH1 mutations. PCD with normal ultrastructure exhibits heterogeneous HSV values, but mostly an increased CBF with an extremely high maximal CBF.ConclusionQuantitative HSV analysis in PCD objectives beating anomalies associated with specific ciliary ultrastructures and genotypes. It represents a promising approach to guide the molecular analyses towards the best candidate gene(s) to be analysed or to assess the pathogenicity of the numerous sequence variants identified by next-generation-sequencing.

scholarly journals Ciliary beat pattern and frequency in genetic variants of primary ciliary dyskinesia

2014 ◽  
Vol 44 (6) ◽  
pp. 1579-1588 ◽  
Author(s):  
Johanna Raidt ◽  
Julia Wallmeier ◽  
Rim Hjeij ◽  
Jörg Große Onnebrink ◽  
Petra Pennekamp ◽  
...  
Keyword(s):  
Primary Ciliary Dyskinesia ◽  
High Speed ◽  
Genetic Disorder ◽  
Beat Frequency ◽  
Detailed Knowledge ◽  
Beat Pattern ◽  
Biallelic Mutations ◽  
Tract Infections ◽  
Ciliary Dyskinesia ◽  
Ciliary Beat

Primary ciliary dyskinesia (PCD) is a rare genetic disorder leading to recurrent respiratory tract infections. High-speed video-microscopy analysis (HVMA) of ciliary beating, currently the first-line diagnostic tool for PCD in most centres, is challenging because recent studies have expanded the spectrum of HVMA findings in PCD from grossly abnormal to very subtle. The objective of this study was to describe the diversity of HVMA findings in genetically confirmed PCD individuals.HVMA was performed as part of the routine work-up of individuals with suspected PCD. Subsequent molecular analysis identified biallelic mutations in the PCD-related genes of 66 individuals. 1072 videos of these subjects were assessed for correlation with the genotype.Biallelic mutations (19 novel) were found in 17 genes: DNAI1, DNAI2, DNAH5, DNAH11, CCDC103, ARMC4, KTU/DNAAF2, LRRC50/DNAAF1, LRRC6, DYX1C1, ZMYND10, CCDC39, CCDC40, CCDC164, HYDIN, RSPH4A and RSPH1. Ciliary beat pattern variations correlated well with the genetic findings, allowing the classification of typical HVMA findings for different genetic groups. In contrast, analysis of ciliary beat frequency did not result in additional diagnostic impact.In conclusion, this study provides detailed knowledge about the diversity of HVMA findings in PCD and may therefore be seen as a guide to the improvement of PCD diagnostics.

Sinus surgery can improve quality of life, lung infections, and lung function in patients with primary ciliary dyskinesia

2016 ◽  
Vol 7 (3) ◽  
pp. 240-247 ◽  
Author(s):  
Mikkel Christian Alanin ◽  
Kasper Aanaes ◽  
Niels Høiby ◽  
Tania Pressler ◽  
Marianne Skov ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Lung Function ◽  
Primary Ciliary Dyskinesia ◽  
Sinus Surgery ◽  
Improve Quality ◽  
Lung Infections ◽  
Ciliary Dyskinesia

scholarly journals C11orf70 mutations causing primary ciliary dyskinesia disrupt a conserved step in the intraflagellar transport-dependent assembly of multiple axonemal dyneins

2017 ◽  
Author(s):  
Mahmoud R. Fassad ◽  
Amelia Shoemark ◽  
Pierrick le Borgne ◽  
France Koll ◽  
Mitali Patel ◽  
...  
Keyword(s):  
Primary Ciliary Dyskinesia ◽  
Intraflagellar Transport ◽  
Similar Distribution ◽  
Targeted Next Generation Sequencing ◽  
Respiratory Cilia ◽  
Dynein Arms ◽  
Active Transport Process ◽  
Cytoplasmic Assembly ◽  
Ciliary Dyskinesia ◽  
Generation Sequencing

AbstractPrimary ciliary dyskinesia (PCD) is a genetically and phenotypically heterogeneous disorder characterized by destructive respiratory disease and laterality abnormalities due to randomised left-right body asymmetry. PCD is mostly caused by mutations affecting components of the core axoneme structure of motile cilia that are essential for cilia movement. In addition, there is a growing group of PCD genes that encode proteins essential for the assembly of the ciliary dynein motors and the active transport process that delivers them from their cytoplasmic assembly site into the axoneme. We screened a cohort of affected individuals for disease-causing mutations using a targeted next generation sequencing panel and identified 2 unrelated families (3 affected children) with mutations in the uncharacterized C11orf70 gene. The affected children share a consistent PCD phenotype from early life with laterality defects and immotile respiratory cilia displaying combined loss of inner and outer dynein arms (IDA+ODA). Phylogenetic analysis shows C11orf70 is highly conserved, distributed across species similarly to proteins involved in the intraflagellar transport (IFT)-dependant assembly of axonemal dyneins. Paramecium C11orf70 RNAi knockdown led to combined loss of ciliary IDA+ODA with reduced cilia beating and swim velocity. Fluorescently tagged C11orf70 in Paramecium and Chlamydomonas localises mainly in the cytoplasm with a small amount in the ciliary component, its abundance in the axoneme being IFT-dependant. During ciliogenesis, C11orf70 accumulates at the ciliary tips in a similar distribution to the IFT-B protein IFT46. In summary, C11orf70 is essential for IFT-dependant assembly of dynein arms and C11orf70 mutations cause defective cilia motility and PCD.

scholarly journals Olfactory dysfunction is worse in primary ciliary dyskinesia compared with other causes of chronic sinusitis in children

Thorax ◽  
2018 ◽  
Vol 73 (10) ◽  
pp. 980-982 ◽  
Author(s):  
Massimo Pifferi ◽  
Andrew Bush ◽  
Michele Rizzo ◽  
Alessandro Tonacci ◽  
Maria Di Cicco ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Primary Ciliary Dyskinesia ◽  
Chronic Sinusitis ◽  
Olfactory Dysfunction ◽  
Healthy Controls ◽  
Sinus Disease ◽  
Multiple Functions ◽  
Nasal Nitric Oxide ◽  
Transmission Electron ◽  
Ciliary Dyskinesia

Cilia have multiple functions including olfaction. We hypothesised that olfactory function could be impaired in primary ciliary dyskinesia (PCD). Olfaction, nasal nitric oxide (nNO) and sinus CT were assessed in patients with PCD and non-PCD sinus disease, and healthy controls (no CT scan). PCD and non-PCD patients had similar severity of sinus disease. Despite this, defective olfaction was more common in patients with PCD (P<0.0001) and more severe in patients with PCD with major Transmission Electron Microscopy (TEM) abnormalities. Only in classical PCD did olfaction inversely correlate with sinusitis and nNO. We speculate that defective olfaction in PCD is primary in nature.

scholarly journals Chromothripsis: Basis of a Concurrent Unusual Association between Myelodysplastic Syndrome and Primary Ciliary Dyskinesia

2014 ◽  
Vol 2014 ◽  
pp. 1-5
Author(s):  
Abhinav Agrawal ◽  
Anar Modi ◽  
Sayee Sundar Alagusundaramoorthy ◽  
Wael Ghali
Keyword(s):  
Myelodysplastic Syndrome ◽  
Primary Ciliary Dyskinesia ◽  
Marrow Transplant ◽  
Sinus Disease ◽  
Unusual Association ◽  
First Case ◽  
Advanced Stages ◽  
Clinical Conditions ◽  
Time Of Presentation ◽  
Ciliary Dyskinesia

A 20 year old male was initially diagnosed suffering from Primary ciliary dyskinesia with symptoms of bronchiectasis, severe frontal, maxillary and ethmoid sinus disease. At the age of 20, the patient was also diagnosed with Myelodysplastic syndrome requiring Bone marrow transplant due to the advanced stage at time of presentation. Primary ciliary dyskinesia and Myelodsyplastic syndrome are both rare clinical conditions found in the general population, especially in young adults. This rare combination of disorders has never been reported in literature to the best of the author’s knowledge. The presence of an advanced cancer and a genetic abnormality due to two deletions occurring in two arms of the same chromosome can be explained on the base of chromothripsis. A number of evidences have been published in the literature, about multiple deletions in chromosome 5 and advanced stages of MDS being associated with chromothripsis however this is the first case report on two deletions in chromosome 7 giving rise to two different clinical entities requiring multiple modes of management.

Minitrephination as an Adjunctive Measure in the Endoscopic Management of Complex Frontal Sinus Disease

2007 ◽  
Vol 21 (5) ◽  
pp. 629-636 ◽  
Author(s):  
Alen N. Cohen ◽  
Marilene B. Wang
Keyword(s):  
Los Angeles ◽  
Frontal Sinus ◽  
Medical Center ◽  
Retrospective Chart Review ◽  
Sinus Surgery ◽  
Endoscopic Management ◽  
Fungal Sinusitis ◽  
Allergic Fungal Sinusitis ◽  
Sinus Disease

Background Frontal sinus disease and its surgical management continues to remain an area of controversy among rhinologists. This is evidenced by the multitude of surgical procedures, both external and endoscopic, that have been developed in its management. This study was performed to evaluate the safety and efficacy of frontal sinus minitrephination in combination with endoscopic frontal sinus exploration for the management of complex frontal sinus disease. Methods A retrospective chart review identified 13 patients treated with minitrephination, in conjunction with endoscopic frontal sinus exploration, at the University of California at Los Angeles Medical Center or West Los Angeles VA Medical Center from July 2004 to October 2005. Results Thirteen patients with diagnoses of chronic sinusitis (n = 10), nasal polyposis (n = 7), frontal mucocele (n = 4), allergic fungal sinusitis (n = 3), and inverting papilloma (n = 1) underwent either unilateral (n = 9) or bilateral (n = 4) minitrephination during primary or revision functional endoscopic sinus surgery. Median follow-up was 14.2 months. There were no complications attributed to the procedure, and all patients had improvement of their sinus symptoms and displayed no evidence of recurrence of their frontal sinus disease at last follow-up. Conclusion Minitrephination is a safe and effective adjunct in the management of complex frontal sinus disease, as it allows identification of the frontal recess and vigorous irrigation of the sinus contents.

scholarly journals Diagnosis of primary ciliary dyskinesia

2015 ◽  
Vol 41 (3) ◽  
pp. 251-263 ◽  
Author(s):  
Mary Anne Kowal Olm ◽  
Elia Garcia Caldini ◽  
Thais Mauad
Keyword(s):  
Primary Ciliary Dyskinesia ◽  
Bacterial Colonization ◽  
Genetic Disorder ◽  
Signs And Symptoms ◽  
Screening Tests ◽  
Lower Airway ◽  
Airway Infections ◽  
Means Of Transmission ◽  
Respiratory Signs And Symptoms ◽  
Ciliary Dyskinesia

Primary ciliary dyskinesia (PCD) is a genetic disorder of ciliary structure or function. It results in mucus accumulation and bacterial colonization of the respiratory tract which leads to chronic upper and lower airway infections, organ laterality defects, and fertility problems. We review the respiratory signs and symptoms of PCD, as well as the screening tests for and diagnostic investigation of the disease, together with details related to ciliary function, ciliary ultrastructure, and genetic studies. In addition, we describe the difficulties in diagnosing PCD by means of transmission electron microscopy, as well as describing patient follow-up procedures.

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