Is the sensitivity of primary ciliary dyskinesia detection by ciliary function analysis 100%?: Table 1–

Measuring nasal nitric oxide (nNO) is increasingly used as part of testing for primary ciliary dyskinesia (PCD). The diagnosis of PCD is often delayed until after bronchiectasis is established and auditory damage has occurred. It is important that all paediatricians are aware of clinical features that are suggestive of PCD that should prompt diagnostic testing. nNO levels are recognised to be low in people with PCD and results generated by static chemiluminescence analysers using velum closure technique in older children have good sensitivity and specificity. However, to conclusively rule PCD in or out, further tests of ciliary function are required and assessment of cilia ultrastructure, immunohistochemistry studies and genotyping may also be indicated. These tests are more complex, invasive and expensive than nNO. nNO is less well studied in younger children where tidal breathing measurements are required. Portable nitric oxide analysers are also increasingly used in practice. This paper discusses when to consider PCD as a possible diagnosis in a child along with the indications, physiological and technical background and clinical utility of nNO as a test for PCD in children.

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

Circulation ◽

10.1161/circ.116.suppl_16.ii_83 ◽

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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The Evaluation of Ciliary Function: Electron versus Light Microscopy

American Journal of Rhinology ◽

10.2500/105065898781390172 ◽

1998 ◽

Vol 12 (3) ◽

pp. 199-202 ◽

Cited By ~ 5

Author(s):

Stephen B. Kupferberg ◽

John P. Bent ◽

Edward S. Porubsky

Keyword(s):

Electron Microscopy ◽

Light Microscopy ◽

Primary Ciliary Dyskinesia ◽

Imaging Techniques ◽

Electron Microscopic Examination ◽

Definitive Diagnosis ◽

Electron Microscopic ◽

Ciliary Function ◽

Physical Findings ◽

Ciliary Dyskinesia

Diagnosing Primary Ciliary Dyskinesia can often be difficult. Physical findings suggest the disease, but definitive diagnosis should be made with a ciliary biopsy. Twenty biopsies were obtained from 16 patients and all underwent both light and electron microscopic examination. In 8/20 (40%) there was a discrepancy between the different imaging techniques. Therefore, light microscopy should be used to assess adequacy of biopsy and motion of the cilia along with electron microscopy to examine ultrastructure.

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Ciliary function and the treatment of primary ciliary dyskinesia

Paediatric Respiratory Reviews ◽

10.1016/s1526-0542(10)70049-x ◽

2010 ◽

Vol 11 ◽

pp. S40

Author(s):

C. O'Callaghan

Keyword(s):

Primary Ciliary Dyskinesia ◽

Ciliary Function ◽

Ciliary Dyskinesia

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Primary ciliary dyskinesia relative protein ZMYND10 is involved in regulating ciliary function and intraflagellar transport in Paramecium tetraurelia

European Journal of Protistology ◽

10.1016/j.ejop.2020.125756 ◽

2021 ◽

Vol 77 ◽

pp. 125756

Author(s):

Lei Shi ◽

Xiangyu Shen ◽

Yuhao Chi ◽

Yuan Shen

Keyword(s):

Primary Ciliary Dyskinesia ◽

Intraflagellar Transport ◽

Paramecium Tetraurelia ◽

Ciliary Function ◽

Ciliary Dyskinesia

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Diagnosis of primary ciliary dyskinesia: potential options for resource-limited countries

European Respiratory Review ◽

10.1183/16000617.0058-2016 ◽

2017 ◽

Vol 26 (143) ◽

pp. 160058 ◽

Cited By ~ 8

Author(s):

Nisreen Rumman ◽

Claire Jackson ◽

Samuel Collins ◽

Patricia Goggin ◽

Janice Coles ◽

...

Keyword(s):

Diagnostic Tests ◽

Primary Ciliary Dyskinesia ◽

High Speed ◽

Care Setting ◽

Nasal Nitric Oxide ◽

Ciliary Function ◽

Resource Limited ◽

Transmission Electron ◽

Sophisticated Equipment ◽

Ciliary Dyskinesia

Primary ciliary dyskinesia is a genetic disease of ciliary function leading to chronic upper and lower respiratory tract symptoms. The diagnosis is frequently overlooked because the symptoms are nonspecific and the knowledge about the disease in the primary care setting is poor. Additionally, none of the available tests is accurate enough to be used in isolation. These tests are expensive, and need sophisticated equipment and expertise to analyse and interpret results; diagnosis is therefore only available at highly specialised centres. The diagnosis is particularly challenging in countries with limited resources due to the lack of such costly equipment and expertise.In this review, we discuss the importance of early and accurate diagnosis especially for countries where the disease is clinically prevalent but diagnostic tests are lacking. We review the diagnostic tests available in specialised centres (nasal nitric oxide, high-speed video microscopy, transmission electron microscopy, immunofluorescence and genetics). We then consider modifications that might be considered in less well-resourced countries whilst maintaining acceptable accuracy.

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Ependymal ciliary motion and their role in congenital hydrocephalus

Child s Nervous System ◽

10.1007/s00381-021-05194-9 ◽

2021 ◽

Author(s):

Koichiro Sakamoto ◽

Madoka Nakajima ◽

Kaito Kawamura ◽

Eri Nakamura ◽

Norihiro Tada ◽

...

Keyword(s):

Clinical Practice ◽

Animal Models ◽

Knockout Mice ◽

Primary Ciliary Dyskinesia ◽

Congenital Hydrocephalus ◽

Genetic Mutations ◽

Ciliary Function ◽

Ciliary Motion ◽

Ciliary Dyskinesia

Abstract Purpose Since a case of hydrocephalus in humans considered to be caused by ciliary dysfunction was first reported by Greenstone et al. in 1984, numerous papers on the correlation between ciliary function and hydrocephalus have been published. Methods We reviewed the published literature on primary ciliary dyskinesia in humans causing hydrocephalus, focusing on articles specifically examining the relation between ciliary function and hydrocephalus and its treatment. In addition, the authors’ experience is briefly discussed. Results Full texts of 16 articles reporting cases of human hydrocephalus (including ventriculomegaly) due to defects in ependymal ciliary function or primary ciliary dyskinesia observed in clinical practice were extracted. In recent years, studies on animal models, especially employing knockout mice, have revealed genetic mutations that cause hydrocephalus via ciliary dysfunction. However, a few reports on the onset of hydrocephalus in human patients with primary ciliary dyskinesia have confirmed that the incidence of this condition was extremely low compared to that in animal models. Conclusion In humans, it is rare for hydrocephalus to develop solely because of abnormalities in the cilia, and it is highly likely that other factors are also involved along with ciliary dysfunction.

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Critical Evaluation of Sinonasal Disease in 64 Adults with Primary Ciliary Dyskinesia

Journal of Clinical Medicine ◽

10.3390/jcm8050619 ◽

2019 ◽

Vol 8 (5) ◽

pp. 619 ◽

Cited By ~ 9

Author(s):

Emilie Bequignon ◽

Laurence Dupuy ◽

Francoise Zerah-Lancner ◽

Laurence Bassinet ◽

Isabelle Honoré ◽

...

Keyword(s):

Hearing Loss ◽

Primary Ciliary Dyskinesia ◽

Otitis Media With Effusion ◽

Critical Evaluation ◽

Forced Expiratory Volume ◽

Clinical Feature ◽

Ciliary Function ◽

Symptom Scores ◽

Ciliary Dyskinesia ◽

Nose And Throat

To date, no study precisely described ear, nose and throat (ENT) disease in adults with primary ciliary dyskinesia (PCD) and its relationship with ciliary function/ultrastructure. A retrospective study of standardized ENT data (exam, audiogram, sinus Computed tomography (CT), and bacteriology) was conducted in 64 adults with confirmed PCD who were followed in two ENT reference centers. Rhinorrhoea and hearing loss were the main symptoms. Symptom scores were higher in older patients. Nasal endoscopy was abnormal in all patients except one, showing nasal polyps in one-third of the patients and stagnant nasal mucus secretions in 87.5% of the patients. Sinus CT opacities were mainly incomplete and showed one-third of the patients with sinus hypoplasia and/or agenesis. Middle meatus mainly grew Haemophilus influenzae, Streptoccocus pneumoniae and Pseudomonas aeruginosa. Otitis media with effusion (OME), which is constant in childhood, was diagnosed in less than one-quarter of the patients. In two-thirds of the patients, audiogram showed hearing loss that was sensorineural in half of the patients. ENT disease severity was not correlated with ciliary function and ultrastructure, but the presence of OME was significantly associated with a forced expiratory volume (FEV1) < 70%. Rhinosinusitis is the most common clinical feature of PCD in adults, while OME is less frequent. The presence of active OME in adults with PCD could be a severity marker of lung function and lead to closer monitoring.

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