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Margaret W Leigh - One of the best experts on this subject based on the ideXlab platform.
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Primary Ciliary Dyskinesia
Clinics in Chest Medicine, 2016Co-Authors: Michael R. Knowles, Maimoona A. Zariwala, Margaret W LeighAbstract:Primary Ciliary Dyskinesia (PCD) is a recessive genetically heterogeneous disorder of motile cilia with chronic otosinopulmonary disease and organ laterality defects in ∼50% of cases. The prevalence of PCD is difficult to determine. Recent diagnostic advances through measurement of nasal nitric oxide and genetic testing has allowed rigorous diagnoses and determination of a robust clinical phenotype, which includes neonatal respiratory distress, daily nasal congestion, and wet cough starting early in life, along with organ laterality defects. There is early onset of lung disease in PCD with abnormal airflow mechanics and radiographic abnormalities detected in infancy and early childhood.
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The prevalence of clinical features associated with Primary Ciliary Dyskinesia in a heterotaxy population: results of a web-based survey
Cardiology in the young, 2014Co-Authors: Adam J Shapiro, Michael R. Knowles, Maimoona A. Zariwala, Sue Tolleson-rinehart, Margaret W LeighAbstract:Primary Ciliary Dyskinesia and heterotaxy are rare but not mutually exclusive disorders, which result from cilia dysfunction. Heterotaxy occurs in at least 12.1% of Primary Ciliary Dyskinesia patients, but the prevalence of Primary Ciliary Dyskinesia within the heterotaxy population is unknown. We designed and distributed a web-based survey to members of an international heterotaxy organisation to determine the prevalence of respiratory features that are common in Primary Ciliary Dyskinesia and that might suggest the possibility of Primary Ciliary Dyskinesia. A total of 49 members (25%) responded, and 37% of the respondents have features suggesting the possibility of Primary Ciliary Dyskinesia, defined as (1) the presence of at least two chronic respiratory symptoms, or (2) bronchiectasis or history of respiratory pathogens suggesting Primary Ciliary Dyskinesia. Of the respondents, four completed comprehensive, in-person evaluations, with definitive Primary Ciliary Dyskinesia confirmed in one individual, and probable Primary Ciliary Dyskinesia identified in two others. The high prevalence of respiratory features compatible with Primary Ciliary Dyskinesia in this heterotaxy population suggests that a subset of heterotaxy patients have dysfunction of respiratory, as well as embryonic nodal cilia. To better assess the possibility of Primary Ciliary Dyskinesia, heterotaxy patients with chronic oto-sino-respiratory symptoms should be referred for a Primary Ciliary Dyskinesia evaluation.
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clinical and genetic aspects of Primary Ciliary Dyskinesia kartagener syndrome
Genetics in Medicine, 2009Co-Authors: Margaret W Leigh, John L. Carson, Michael R. Knowles, Thomas W. Ferkol, Sharon D. Dell, Jessica E Pittman, Stephanie D Davis, Maimoona A. ZariwalaAbstract:Primary Ciliary Dyskinesia is a genetically heterogeneous disorder of motile cilia. Most of the disease-causing mutations identified to date involve the heavy (dynein axonemal heavy chain 5) or intermediate(dynein axonemal intermediate chain 1) chain dynein genes in Ciliary outer dynein arms, although a few mutations have been noted in other genes. Clinical molecular genetic testing for Primary Ciliary Dyskinesia is available for the most common mutations. The respiratory manifestations of Primary Ciliary Dyskinesia (chronic bronchitis leading to bronchiectasis, chronic rhino-sinusitis, and chronic otitis media)reflect impaired mucoCiliary clearance owing to defective axonemal structure. Ciliary ultrastructural analysis in most patients (>80%) reveals defective dynein arms, although defects in other axonemal components have also been observed. Approximately 50% of patients with Primary Ciliary Dyskinesia have laterality defects (including situs inversus totalis and, less commonly, heterotaxy, and congenital heart disease),reflecting dysfunction of embryological nodal cilia. Male infertility is common and reflects defects in sperm tail axonemes. Most patients with Primary Ciliary Dyskinesia have a history of neonatal respiratory distress, suggesting that motile cilia play a role in fluid clearance during the transition from a fetal to neonatal lung. Ciliopathies involving sensory cilia, including autosomal dominant or recessive polycystic kidney disease, Bardet-Biedl syndrome, and Alstrom syndrome, may have chronic respiratory symptoms and even bronchiectasis suggesting clinical overlap with Primary Ciliary Dyskinesia.
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Clinical and genetic aspects of Primary Ciliary Dyskinesia/Kartagener syndrome
Genetics in Medicine, 2009Co-Authors: Margaret W Leigh, John L. Carson, Michael R. Knowles, Thomas W. Ferkol, Sharon D. Dell, Jessica E Pittman, Stephanie D Davis, Maimoona A. ZariwalaAbstract:Primary Ciliary Dyskinesia is a genetically heterogeneous disorder of motile cilia. Most of the disease-causing mutations identified to date involve the heavy ( dynein axonemal heavy chain 5 ) or intermediate ( dynein axonemal intermediate chain 1 ) chain dynein genes in Ciliary outer dynein arms, although a few mutations have been noted in other genes. Clinical molecular genetic testing for Primary Ciliary Dyskinesia is available for the most common mutations. The respiratory manifestations of Primary Ciliary Dyskinesia (chronic bronchitis leading to bronchiectasis, chronic rhino-sinusitis, and chronic otitis media) reflect impaired mucoCiliary clearance owing to defective axonemal structure. Ciliary ultrastructural analysis in most patients (>80%) reveals defective dynein arms, although defects in other axonemal components have also been observed. Approximately 50% of patients with Primary Ciliary Dyskinesia have laterality defects (including situs inversus totalis and, less commonly, heterotaxy, and congenital heart disease), reflecting dysfunction of embryological nodal cilia. Male infertility is common and reflects defects in sperm tail axonemes. Most patients with Primary Ciliary Dyskinesia have a history of neonatal respiratory distress, suggesting that motile cilia play a role in fluid clearance during the transition from a fetal to neonatal lung. Ciliopathies involving sensory cilia, including autosomal dominant or recessive polycystic kidney disease, Bardet-Biedl syndrome, and Alstrom syndrome, may have chronic respiratory symptoms and even bronchiectasis suggesting clinical overlap with Primary Ciliary Dyskinesia.
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Primary Ciliary Dyskinesia: improving the diagnostic approach
Current opinion in pediatrics, 2009Co-Authors: Margaret W Leigh, Maimoona A. Zariwala, Michael R. KnowlesAbstract:Purpose of reviewThe diagnosis of Primary Ciliary Dyskinesia (PCD) has relied on analysis of Ciliary motility and ultrastructure; however, these tests are not readily available and have not been standardized. Consequently, the diagnosis of PCD may be delayed or missed or made incorrectly. This revie
Sharon D. Dell - One of the best experts on this subject based on the ideXlab platform.
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Primary Ciliary Dyskinesia longitudinal study of lung disease by ultrastructure defect and genotype
American Journal of Respiratory and Critical Care Medicine, 2019Co-Authors: Stephanie D Davis, Thomas W. Ferkol, Sharon D. Dell, Jessica E Pittman, Margaret Rosenfeld, Hyeseung Lee, Scott D Sagel, Carlos Milla, Adam J Shapiro, Kelli M SullivanAbstract:Rationale: In Primary Ciliary Dyskinesia, factors leading to disease heterogeneity are poorly understood.Objectives: To describe early lung disease progression in Primary Ciliary Dyskinesia and ide...
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Primary Ciliary Dyskinesia: mechanisms and management
The application of clinical genetics, 2017Co-Authors: Nadirah Damseh, Nada Quercia, Nisreen Rumman, Sharon D. Dell, Raymond H. KimAbstract:Primary Ciliary Dyskinesia is a genetically heterogeneous disorder of motile cilia that is predominantly inherited in an autosomal-recessive fashion. It is associated with abnormal Ciliary structure and/or function leading to chronic upper and lower respiratory tract infections, male infertility, and situs inversus. The estimated prevalence of Primary Ciliary Dyskinesia is approximately one in 10,000-40,000 live births. Diagnosis depends on clinical presentation, nasal nitric oxide, high-speed video-microscopy analysis, transmission electron microscopy, genetic testing, and immunofluorescence. Here, we review its clinical features, diagnostic methods, molecular basis, and available therapies.
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Treatment recommendations in Primary Ciliary Dyskinesia.
Paediatric respiratory reviews, 2015Co-Authors: Deepika Polineni, Stephanie D Davis, Sharon D. DellAbstract:Primary Ciliary Dyskinesia (PCD) is a rare heterogenic disorder leading to significant respiratory morbidity. Health-care providers who treat PCD must familiarize themselves with recommended treatment strategies. However, most of the treatments recommended in PCD have been extrapolated from cystic fibrosis (CF) and non-CF bronchiectasis literature. Mainstays of therapy are reviewed in detail, and should include at a minimum: regular airway clearance, routine microbiological surveillance, antibiotic treatment for pulmonary exacerbation, and health vaccinations. This review summarizes both medical and surgical pulmonary treatment considerations, as well as recommendations for the integration of non-pulmonary subspecialty care in the management of PCD.
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clinical and genetic aspects of Primary Ciliary Dyskinesia kartagener syndrome
Genetics in Medicine, 2009Co-Authors: Margaret W Leigh, John L. Carson, Michael R. Knowles, Thomas W. Ferkol, Sharon D. Dell, Jessica E Pittman, Stephanie D Davis, Maimoona A. ZariwalaAbstract:Primary Ciliary Dyskinesia is a genetically heterogeneous disorder of motile cilia. Most of the disease-causing mutations identified to date involve the heavy (dynein axonemal heavy chain 5) or intermediate(dynein axonemal intermediate chain 1) chain dynein genes in Ciliary outer dynein arms, although a few mutations have been noted in other genes. Clinical molecular genetic testing for Primary Ciliary Dyskinesia is available for the most common mutations. The respiratory manifestations of Primary Ciliary Dyskinesia (chronic bronchitis leading to bronchiectasis, chronic rhino-sinusitis, and chronic otitis media)reflect impaired mucoCiliary clearance owing to defective axonemal structure. Ciliary ultrastructural analysis in most patients (>80%) reveals defective dynein arms, although defects in other axonemal components have also been observed. Approximately 50% of patients with Primary Ciliary Dyskinesia have laterality defects (including situs inversus totalis and, less commonly, heterotaxy, and congenital heart disease),reflecting dysfunction of embryological nodal cilia. Male infertility is common and reflects defects in sperm tail axonemes. Most patients with Primary Ciliary Dyskinesia have a history of neonatal respiratory distress, suggesting that motile cilia play a role in fluid clearance during the transition from a fetal to neonatal lung. Ciliopathies involving sensory cilia, including autosomal dominant or recessive polycystic kidney disease, Bardet-Biedl syndrome, and Alstrom syndrome, may have chronic respiratory symptoms and even bronchiectasis suggesting clinical overlap with Primary Ciliary Dyskinesia.
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Clinical and genetic aspects of Primary Ciliary Dyskinesia/Kartagener syndrome
Genetics in Medicine, 2009Co-Authors: Margaret W Leigh, John L. Carson, Michael R. Knowles, Thomas W. Ferkol, Sharon D. Dell, Jessica E Pittman, Stephanie D Davis, Maimoona A. ZariwalaAbstract:Primary Ciliary Dyskinesia is a genetically heterogeneous disorder of motile cilia. Most of the disease-causing mutations identified to date involve the heavy ( dynein axonemal heavy chain 5 ) or intermediate ( dynein axonemal intermediate chain 1 ) chain dynein genes in Ciliary outer dynein arms, although a few mutations have been noted in other genes. Clinical molecular genetic testing for Primary Ciliary Dyskinesia is available for the most common mutations. The respiratory manifestations of Primary Ciliary Dyskinesia (chronic bronchitis leading to bronchiectasis, chronic rhino-sinusitis, and chronic otitis media) reflect impaired mucoCiliary clearance owing to defective axonemal structure. Ciliary ultrastructural analysis in most patients (>80%) reveals defective dynein arms, although defects in other axonemal components have also been observed. Approximately 50% of patients with Primary Ciliary Dyskinesia have laterality defects (including situs inversus totalis and, less commonly, heterotaxy, and congenital heart disease), reflecting dysfunction of embryological nodal cilia. Male infertility is common and reflects defects in sperm tail axonemes. Most patients with Primary Ciliary Dyskinesia have a history of neonatal respiratory distress, suggesting that motile cilia play a role in fluid clearance during the transition from a fetal to neonatal lung. Ciliopathies involving sensory cilia, including autosomal dominant or recessive polycystic kidney disease, Bardet-Biedl syndrome, and Alstrom syndrome, may have chronic respiratory symptoms and even bronchiectasis suggesting clinical overlap with Primary Ciliary Dyskinesia.
Maimoona A. Zariwala - One of the best experts on this subject based on the ideXlab platform.
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Primary Ciliary Dyskinesia
Clinics in Chest Medicine, 2016Co-Authors: Michael R. Knowles, Maimoona A. Zariwala, Margaret W LeighAbstract:Primary Ciliary Dyskinesia (PCD) is a recessive genetically heterogeneous disorder of motile cilia with chronic otosinopulmonary disease and organ laterality defects in ∼50% of cases. The prevalence of PCD is difficult to determine. Recent diagnostic advances through measurement of nasal nitric oxide and genetic testing has allowed rigorous diagnoses and determination of a robust clinical phenotype, which includes neonatal respiratory distress, daily nasal congestion, and wet cough starting early in life, along with organ laterality defects. There is early onset of lung disease in PCD with abnormal airflow mechanics and radiographic abnormalities detected in infancy and early childhood.
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Primary Ciliary Dyskinesia.
Seminars in respiratory and critical care medicine, 2015Co-Authors: Jason Lobo, Maimoona A. Zariwala, Peadar G. NooneAbstract:Primary Ciliary Dyskinesia (PCD) is an autosomal recessive disorder of cilia structure, function, and biogenesis leading to chronic infections of the respiratory tract, fertility problems, and disorders of organ laterality. The diagnosis can be challenging, using traditional tools such as characteristic clinical features, Ciliary function, and ultrastructural defects and newer screening tools such as nasal nitric oxide levels and genetic testing add to the diagnostic algorithm. There are 32 known PCD-causing genes, and in the future, comprehensive genetic testing may screen young infants before developing symptoms, thus improving survival. Therapies include surveillance of pulmonary function and microbiology, in addition to airway clearance, antibiotics, and early referral to bronchiectasis centers. As with cystic fibrosis (CF), standardized care at specialized centers using a multidisciplinary approach likely improves outcomes. In conjunction with the CF foundation, the PCD foundation, with experienced investigators and clinicians, is developing a network of PCD clinical centers to coordinate the effort in North America and Europe. As the network grows, clinical care and knowledge will improve.
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Primary Ciliary Dyskinesia
QJM: An International Journal of Medicine, 2014Co-Authors: Leonard J Lobo, Maimoona A. Zariwala, Peadar G. NooneAbstract:Primary Ciliary Dyskinesia (PCD) is an autosomal recessive disorder of cilia structure and function, leading to chronic infections of the respiratory tract, fertility problems and disorders of organ laterality. Making a definitive diagnosis is challenging, utilizing characteristic phenotypes, Ciliary functional and ultra-structural defects in addition to newer screening tools such as nasal nitric oxide and genetic testing. There are 21 known PCD causing genes and in the future, comprehensive genetic testing may help diagnosis young infants prior to developing symptoms thus improving survival. Therapy includes surveillance of pulmonary function and microbiology in addition to, airway clearance, antibiotics and early referral to bronchiectasis centers. Standardized care at specialized centers using a multidisciplinary approach is likely to improve outcomes. In conjunction with the PCD foundation and lead investigators and clinicians are developing a network of PCD clinical centers to coordinate the effort in North America and Europe. As the network grows, care and knowledge will undoubtedly improve.
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The prevalence of clinical features associated with Primary Ciliary Dyskinesia in a heterotaxy population: results of a web-based survey
Cardiology in the young, 2014Co-Authors: Adam J Shapiro, Michael R. Knowles, Maimoona A. Zariwala, Sue Tolleson-rinehart, Margaret W LeighAbstract:Primary Ciliary Dyskinesia and heterotaxy are rare but not mutually exclusive disorders, which result from cilia dysfunction. Heterotaxy occurs in at least 12.1% of Primary Ciliary Dyskinesia patients, but the prevalence of Primary Ciliary Dyskinesia within the heterotaxy population is unknown. We designed and distributed a web-based survey to members of an international heterotaxy organisation to determine the prevalence of respiratory features that are common in Primary Ciliary Dyskinesia and that might suggest the possibility of Primary Ciliary Dyskinesia. A total of 49 members (25%) responded, and 37% of the respondents have features suggesting the possibility of Primary Ciliary Dyskinesia, defined as (1) the presence of at least two chronic respiratory symptoms, or (2) bronchiectasis or history of respiratory pathogens suggesting Primary Ciliary Dyskinesia. Of the respondents, four completed comprehensive, in-person evaluations, with definitive Primary Ciliary Dyskinesia confirmed in one individual, and probable Primary Ciliary Dyskinesia identified in two others. The high prevalence of respiratory features compatible with Primary Ciliary Dyskinesia in this heterotaxy population suggests that a subset of heterotaxy patients have dysfunction of respiratory, as well as embryonic nodal cilia. To better assess the possibility of Primary Ciliary Dyskinesia, heterotaxy patients with chronic oto-sino-respiratory symptoms should be referred for a Primary Ciliary Dyskinesia evaluation.
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Primary Ciliary Dyskinesia in Amish communities
The Journal of pediatrics, 2010Co-Authors: Hauw Lie, Maimoona A. Zariwala, Cynthia Helms, Anne M. Bowcock, John L. Carson, David E. Brown, Milan J. Hazucha, James W. Forsen, David W. Molter, Michael R. KnowlesAbstract:Primary Ciliary Dyskinesia is an autosomal recessive multigenic disease that results in impaired mucoCiliary clearance. We have diagnosed 9 subjects with Primary Ciliary Dyskinesia from geographically dispersed Amish communities, on the basis of clinical characteristics and Ciliary ultrastructural defects. Despite consanguinity, affected individuals had evidence of genetic heterogeneity.
Jane S. Lucas - One of the best experts on this subject based on the ideXlab platform.
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Primary Ciliary Dyskinesia in the genomics age
The Lancet. Respiratory medicine, 2019Co-Authors: Jane S. Lucas, Stephanie D Davis, Heymut Omran, Amelia ShoemarkAbstract:Primary Ciliary Dyskinesia is a genetically and clinically heterogeneous syndrome. Impaired function of motile cilia causes failure of mucoCiliary clearance. Patients typically present with neonatal respiratory distress of unknown cause and then continue to have a daily wet cough, recurrent chest infections, perennial rhinosinusitis, otitis media with effusion, and bronchiectasis. Approximately 50% of patients have situs inversus, and infertility is common. While understanding of the underlying genetics and disease mechanisms have substantially advanced in recent years, there remains a paucity of evidence for treatment. Next-generation sequencing has increased gene discovery, and mutations in more than 40 genes have been reported to cause Primary Ciliary Dyskinesia, with many other genes likely to be discovered. Increased knowledge of cilia genes is challenging perceptions of the clinical phenotype, as some genes reported in the last 5 years are associated with mild respiratory disease. Developments in genomics and molecular medicine are rapidly improving diagnosis, and a genetic cause can be identified in approximately 70% of patients known to have Primary Ciliary Dyskinesia. Groups are now investigating novel and personalised treatments, although gene therapies are unlikely to be available in the near future.
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The patient's experience of Primary Ciliary Dyskinesia: a systematic review.
Quality of life research : an international journal of quality of life aspects of treatment care and rehabilitation, 2017Co-Authors: Laura Behan, Jane S. Lucas, Bruna Rubbo, Audrey Dunn GalvinAbstract:Background Primary Ciliary Dyskinesia (PCD) is a rare genetic disorder characterised by progressive sinopulmonary disease, with symptoms starting soon after birth. The aim of this study is to critically review, analyse, and synthesise the literature in order to understand the experiences of patients with Primary Ciliary Dyskinesia (PCD) and the impact on health-related quality of life.
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Diagnostic methods in Primary Ciliary Dyskinesia: Mini-symposium: Primary Ciliary Dyskinesia
2017Co-Authors: Jane S. Lucas, Tamara Paff, Patricia Goggin, Eric G. HaarmanAbstract:Diagnosing Primary Ciliary Dyskinesia is difficult. With no reference standard, a combination of tests is needed; most tests require expensive equipment and specialist scientists. We review the advances in diagnostic testing over the past hundred years, with emphasis on recent advances. We particularly focus on use of high-speed video analysis, transmission electron microscopy, nasal nitric oxide and genetic testing. We discuss the international efforts that are in place to advance the evidence base for diagnostic tests.
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european respiratory society guidelines for the diagnosis of Primary Ciliary Dyskinesia
European Respiratory Journal, 2017Co-Authors: Jane S. Lucas, Laura Behan, Angelo Barbato, Samuel Collins, Myrofora Goutaki, Daan CaudriAbstract:The diagnosis of Primary Ciliary Dyskinesia is often confirmed with standard, albeit complex and expensive, tests. In many cases, however, the diagnosis remains difficult despite the array of sophisticated diagnostic tests. There is no "gold standard" reference test. Hence, a Task Force supported by the European Respiratory Society has developed this guideline to provide evidence-based recommendations on diagnostic testing, especially in light of new developments in such tests, and the need for robust diagnoses of patients who might enter randomised controlled trials of treatments. The guideline is based on pre-defined questions relevant for clinical care, a systematic review of the literature, and assessment of the evidence using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach. It focuses on clinical presentation, nasal nitric oxide, analysis of Ciliary beat frequency and pattern by high-speed video-microscopy analysis, transmission electron microscopy, genotyping and immunofluorescence. It then used a modified Delphi survey to develop an algorithm for the use of diagnostic tests to definitively confirm and exclude the diagnosis of Primary Ciliary Dyskinesia; and to provide advice when the diagnosis was not conclusive. Finally, this guideline proposes a set of quality criteria for future research on the validity of diagnostic methods for Primary Ciliary Dyskinesia.
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Diagnostic Methods in Primary Ciliary Dyskinesia
Paediatric respiratory reviews, 2015Co-Authors: Jane S. Lucas, Tamara Paff, Patricia Goggin, Eric G. HaarmanAbstract:Diagnosing Primary Ciliary Dyskinesia is difficult. With no reference standard, a combination of tests is needed; most tests require expensive equipment and specialist scientists. We review the advances in diagnostic testing over the past hundred years, with emphasis on recent advances. We particularly focus on use of high-speed video analysis, transmission electron microscopy, nasal nitric oxide and genetic testing. We discuss the international efforts that are in place to advance the evidence base for diagnostic tests.
Stephanie D Davis - One of the best experts on this subject based on the ideXlab platform.
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Primary Ciliary Dyskinesia in the genomics age
The Lancet. Respiratory medicine, 2019Co-Authors: Jane S. Lucas, Stephanie D Davis, Heymut Omran, Amelia ShoemarkAbstract:Primary Ciliary Dyskinesia is a genetically and clinically heterogeneous syndrome. Impaired function of motile cilia causes failure of mucoCiliary clearance. Patients typically present with neonatal respiratory distress of unknown cause and then continue to have a daily wet cough, recurrent chest infections, perennial rhinosinusitis, otitis media with effusion, and bronchiectasis. Approximately 50% of patients have situs inversus, and infertility is common. While understanding of the underlying genetics and disease mechanisms have substantially advanced in recent years, there remains a paucity of evidence for treatment. Next-generation sequencing has increased gene discovery, and mutations in more than 40 genes have been reported to cause Primary Ciliary Dyskinesia, with many other genes likely to be discovered. Increased knowledge of cilia genes is challenging perceptions of the clinical phenotype, as some genes reported in the last 5 years are associated with mild respiratory disease. Developments in genomics and molecular medicine are rapidly improving diagnosis, and a genetic cause can be identified in approximately 70% of patients known to have Primary Ciliary Dyskinesia. Groups are now investigating novel and personalised treatments, although gene therapies are unlikely to be available in the near future.
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Primary Ciliary Dyskinesia longitudinal study of lung disease by ultrastructure defect and genotype
American Journal of Respiratory and Critical Care Medicine, 2019Co-Authors: Stephanie D Davis, Thomas W. Ferkol, Sharon D. Dell, Jessica E Pittman, Margaret Rosenfeld, Hyeseung Lee, Scott D Sagel, Carlos Milla, Adam J Shapiro, Kelli M SullivanAbstract:Rationale: In Primary Ciliary Dyskinesia, factors leading to disease heterogeneity are poorly understood.Objectives: To describe early lung disease progression in Primary Ciliary Dyskinesia and ide...
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Treatment recommendations in Primary Ciliary Dyskinesia.
Paediatric respiratory reviews, 2015Co-Authors: Deepika Polineni, Stephanie D Davis, Sharon D. DellAbstract:Primary Ciliary Dyskinesia (PCD) is a rare heterogenic disorder leading to significant respiratory morbidity. Health-care providers who treat PCD must familiarize themselves with recommended treatment strategies. However, most of the treatments recommended in PCD have been extrapolated from cystic fibrosis (CF) and non-CF bronchiectasis literature. Mainstays of therapy are reviewed in detail, and should include at a minimum: regular airway clearance, routine microbiological surveillance, antibiotic treatment for pulmonary exacerbation, and health vaccinations. This review summarizes both medical and surgical pulmonary treatment considerations, as well as recommendations for the integration of non-pulmonary subspecialty care in the management of PCD.
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clinical and genetic aspects of Primary Ciliary Dyskinesia kartagener syndrome
Genetics in Medicine, 2009Co-Authors: Margaret W Leigh, John L. Carson, Michael R. Knowles, Thomas W. Ferkol, Sharon D. Dell, Jessica E Pittman, Stephanie D Davis, Maimoona A. ZariwalaAbstract:Primary Ciliary Dyskinesia is a genetically heterogeneous disorder of motile cilia. Most of the disease-causing mutations identified to date involve the heavy (dynein axonemal heavy chain 5) or intermediate(dynein axonemal intermediate chain 1) chain dynein genes in Ciliary outer dynein arms, although a few mutations have been noted in other genes. Clinical molecular genetic testing for Primary Ciliary Dyskinesia is available for the most common mutations. The respiratory manifestations of Primary Ciliary Dyskinesia (chronic bronchitis leading to bronchiectasis, chronic rhino-sinusitis, and chronic otitis media)reflect impaired mucoCiliary clearance owing to defective axonemal structure. Ciliary ultrastructural analysis in most patients (>80%) reveals defective dynein arms, although defects in other axonemal components have also been observed. Approximately 50% of patients with Primary Ciliary Dyskinesia have laterality defects (including situs inversus totalis and, less commonly, heterotaxy, and congenital heart disease),reflecting dysfunction of embryological nodal cilia. Male infertility is common and reflects defects in sperm tail axonemes. Most patients with Primary Ciliary Dyskinesia have a history of neonatal respiratory distress, suggesting that motile cilia play a role in fluid clearance during the transition from a fetal to neonatal lung. Ciliopathies involving sensory cilia, including autosomal dominant or recessive polycystic kidney disease, Bardet-Biedl syndrome, and Alstrom syndrome, may have chronic respiratory symptoms and even bronchiectasis suggesting clinical overlap with Primary Ciliary Dyskinesia.
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Clinical and genetic aspects of Primary Ciliary Dyskinesia/Kartagener syndrome
Genetics in Medicine, 2009Co-Authors: Margaret W Leigh, John L. Carson, Michael R. Knowles, Thomas W. Ferkol, Sharon D. Dell, Jessica E Pittman, Stephanie D Davis, Maimoona A. ZariwalaAbstract:Primary Ciliary Dyskinesia is a genetically heterogeneous disorder of motile cilia. Most of the disease-causing mutations identified to date involve the heavy ( dynein axonemal heavy chain 5 ) or intermediate ( dynein axonemal intermediate chain 1 ) chain dynein genes in Ciliary outer dynein arms, although a few mutations have been noted in other genes. Clinical molecular genetic testing for Primary Ciliary Dyskinesia is available for the most common mutations. The respiratory manifestations of Primary Ciliary Dyskinesia (chronic bronchitis leading to bronchiectasis, chronic rhino-sinusitis, and chronic otitis media) reflect impaired mucoCiliary clearance owing to defective axonemal structure. Ciliary ultrastructural analysis in most patients (>80%) reveals defective dynein arms, although defects in other axonemal components have also been observed. Approximately 50% of patients with Primary Ciliary Dyskinesia have laterality defects (including situs inversus totalis and, less commonly, heterotaxy, and congenital heart disease), reflecting dysfunction of embryological nodal cilia. Male infertility is common and reflects defects in sperm tail axonemes. Most patients with Primary Ciliary Dyskinesia have a history of neonatal respiratory distress, suggesting that motile cilia play a role in fluid clearance during the transition from a fetal to neonatal lung. Ciliopathies involving sensory cilia, including autosomal dominant or recessive polycystic kidney disease, Bardet-Biedl syndrome, and Alstrom syndrome, may have chronic respiratory symptoms and even bronchiectasis suggesting clinical overlap with Primary Ciliary Dyskinesia.
