Primary ciliary dyskinesia

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Hafsa Ghaffar, M.B.B.S[2]

Primary ciliary dyskinesiaPCD is an autosomal recessive disorder characterised by functional defects in the cilia resulting in an abnormal mucociliary clearance.Epithelial cells containing motile cilia are localised in the respiratory tree, oviduct, sperms, ventricles of the brain and embryonic node. Defects in the epithelial cells accounts for the majority of symptoms of PCD including sinusitis, otitis media and bronchiectasis. Situs inverses(in some patients) and rarely hydrocephalus. While the understanding of the cellular and molecular mechanisms responsible for these symptoms has progressed recently, genetic analysis has identified mutations in only two axonemal dynein genes that can account for abnormal cilia structure.Nasal nitric oxide Nno is the screening test that could be performed initially to diagnose PCD initially followed by electron microscopy to confirm the diagnosis. Treatment mainly focuses on treating underlying conditions that can exacerbate PCD such as antibiotics for rhino-sinusitis, bronchiectasis, and sinusitis.

In 1981, Rossman and coworkers came up with the term primary ciliary dyskinesia (PCD) because some patients with Kartagener syndrome had cilia that were not immotile but exhibited an uncoordinated and inefficient movement pattern.

There is no established system for the classification of primary ciliary dyskinesia.

In many people with primary ciliary dyskinesia, the cause of the disease is unknown, but the main factor contributing to the pathogenesis is mutations in the proteins forming the cilia which result in the formation of abnormal or immotile cilia. Clearly, cilia have many important functions within the body, defects in these cell structures cause a variety of signs and symptoms.

There are no established causes for Primary ciliary dyskinesia, PCD is related to defects in mucociliary clearance due to abnormal ciliary structure. Mutations in around 46 different genes throughout the genome have been found to be causative. Some of these include DNAH5, CCDC39, DNAI1, CCDC40, DNAH11, ZMYND10, CCDC103, CCDC151 and ARMC4.

Primary ciliary dyskinesia must be differentiated from other conditions that cause infertility, sinusitis, otitis media, and rhinitis.

Primary ciliary dyskinesia (PCD) is generally documented as aetiology of bronchiectasis not only in children or young adults but also in older patients. It is challenging to demonstrate the prevalence of PCD in diverse population with estimates varying between one in 4000 to one in 40,000. PCD is linked with the high levels of consanguinity. Clinical suspicion of PCD is high in these communities, chronic cough and nasal symptoms should rise concern for prompt diagnostic testing.

There are no established risk factors for primary ciliary dyskinesia.

There is insufficient evidence to recommend routine screening for primary ciliary dyskinesia, however patients with persistent sinusitis, rhinitis, and no known aetiology should be screened by nasal nitric oxide test, low levels of nasal nitric oxide is diagnostic of primary ciliary dyskinesia and should prompt further testing with biopsy and ciliary beat pattern(CBP).

The long-term effects of primary ciliary dyskinesia (PCD) are dependent on respiratory symptoms. PCD is not considered to be life-threatening, but persistent lung and airway disease can lead to permanent damage. Recurrent ear infections can lead to hearing loss, which is sometimes permanent, prompt diagnosis and early treatment improve long-term outcomes.

A high level of suspicion is required to warrant early diagnosis and initiation of appropriate management before irreversible lung damage ensues. Diagnostic investigations are complex, requiring expensive arrangements and an experienced team of clinicians and scientists. People with persistent respiratory symptoms such as rhinitis, rhino-sinusitis, infertility, recurrent otitis media should seek medical care and undergo further testing. Nasal nitric oxide levels are low in PCD and should be performed as a screening test. Transmission electron microscopy to assess the ultrastructure of cilia is another important investigation that can confirm the diagnosis.

There is no single diagnostic test for primary ciliary dyskinesia. A combination of the following techniques could contribute to the diagnosis of Primary ciliary dyskinesia.

• Nasal nitric oxide test (nNo)
• Assessment of ciliary ultrastructure by Transmission Electron Microscopy(TEM), Gold standard.
• Ciliary beat frequency CBF and Ciliary beat pattern CBP.
• Radio-aerosol MCC
• Direct video cinematography or oscillography to analyse ciliary beat waveform.
• Bronchial ciliary biopsy.
• Electron microscopy Tomography.
• Semen analysis.

Patients with primary ciliary dyskinesia may present in early infancy with respiratory distress or later in life with chronic bronchitis, persistent rhinorrhea, sinusitis, bronchiectasis, or male infertility.

Primary ciliary dyskinesia PCD has no characteristic physical examination findings, however, any clue to recurrent sinus infections or respiratory distress should raise concern for diagnosing PCD.

There are no diagnostic laboratory findings associated with primary ciliary dyskinesia.

Primary ciliary dyskinesia occasionally presents with dextrocardia and situs inversus totalis, non functioning cilia in the embryonal node could be responsible for this mal positioning. Ecg shows right axis deviation, a finding if present should warrant further testing.

An anterior-posterior or lateral chest x-ray could be helpful in diagnosing changes associated with chronic bronchitis and bronchiectasis in primary ciliary dyskinesia. Additionally, if dextrocardia is present it ca also be found on chest x-ray.

Patients with primary ciliary dyskinesia (PKD) present with bronchiectasis or chronic sinusitis as the initial presentation which in turn leads to further testing and establishing a diagnosis. A High-resolution CT scan is the most sensitive imaging test to diagnose bronchiectasis but it can not differentiate between different aetiologies as bronchiectasis due to PCD vs Cystic fibrosis. HRCT can also interpret dextrocardia if present. If a chest X-ray in any patient is suspicious of bronchiectasis HRCT should be performed to rule out PCD.

MRI scans can assess ventilation defects in patients with primary ciliary dyskinesia PCD, along with dextrocardia if present.

There are no other imaging findings associated with Primary Ciliary Dyskinesia.

There are no other diagnostic studies associated with Primary Ciliary Dyskinesia.

There are no definite treatment options, the goal is to manage associated conditions that can lead to worsening of PCD.

There are no definite treatment options to cure Primary ciliary dyskinesia PCD, the goal is to manage associated conditions that can lead to worsening of PCD such as antibiotics for infections, breathing exercises, spirometry for improved lung function, and drainage of secretions.

There are no established interventions for Primary Ciliary Dyskinesia.

Chronic rhino-sinusitis can predispose to superinfections with Pseudomonas aerurginosa in patients with primary ciliary dyskinesia PCD, endoscopic sinus drainage could facilitate sinus drainage. There is no evidence that suggests the insertion of tympanostomy tubes in cases of recurrent otitis media or otitis media with effusion therefore, regular doctor appointments should be scheduled in order to diagnose conductive hearing loss.

There are no established measures for the primary prevention of primary ciliary dyskinesia.

There are no established measures for the secondary prevention of Primary Ciliary Dyskinesia PCD.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Hafsa Ghaffar, M.B.B.S[2]

In 1981, Rossman and coworkers came up with the term primary ciliary dyskinesia (PCD) because some patients with Kartagener syndrome had cilia that were not immotile but exhibited an uncoordinated and inefficient movement pattern.

In 1981, Rossman and coworkers came up with the term primary ciliary dyskinesia (PCD) because some patients with Kartagener syndrome had cilia that were not immotile but exhibited an uncoordinated and inefficient movement pattern. According to recent nomenclature, all congenital ciliary dyskinesias are classified as primary to differentiate it from acquired ciliary dyskinesia. Studies suggest that PCD is still underdiagnosed and that factors contributing to this may include lack of identification of the clinical presentation, lack of diagnostic centers, and patients that have a normal ultrastructure of cilia on transmission electron microscopy. PCD patients were initially explained by KARTAGENER and STUCKI who noted the familial occurrence of chronic sinusitis, situs inversus and bronchiectasis. In 1976, later AFZELIUS noted the relationship between chronic respiratory problems, male sterility, situs inversus, immotile cilia, and abnormal ciliary ultrastructure. It was discovered afterward that the same clinical phenotype was also seen in patients whose cilia were motile but dyskinetic and the name of the condition changed from “immotile cilia syndrome” to “primary ciliary dyskinesia”.^[1][2]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Hafsa Ghaffar, M.B.B.S[2]

There is no established system for the classification of primary ciliary dyskinesia.

There is no established system for the classification of primary ciliary dyskinesia.

Template:WH Template:WS

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Hafsa Ghaffar, M.B.B.S[2]

In many people with primary ciliary dyskinesia, the cause of the disease is unknown, but the main factor contributing to the pathogenesis is mutations in the proteins forming the cilia which result in the formation of abnormal or immotile cilia. Clearly, cilia have many important functions within the body, defects in these cell structures cause a variety of signs and symptoms.

Cilia are responsible for normal clearance of the respiratory system by organized back and forth motion. It also helps in the left-right axis during embryonal development. Pseudostratified columnar epithelium lines the large airways and contiguous structures, including the Paranasal sinuses, middle ears, and posterior nose. Additionally, brain and fallopian tubes are also lined with ciliated columnar epithelium. In addition, the spermatozoa flagella have a core structure that is similar to cilia. The developed ciliated cell has up to 200 cilia. Each cilium has an arrangement of longitudinal microtubules arranged as 9 doublets formed in an outer circle around a central pair.^[1]

Expression of the NODAL gene in the right arm of the cilia results in congenital abnormalities like situs inverses as compared to mutations in the left arm which ends in PCD without situs inverses. In the respiratory tract, cilia move back and forth in a coordinated to clear mucus. This movement of mucus helps to eliminate fluid, bacteria, and particles from the lungs. Most babies with primary ciliary dyskinesia experience breathing problems at birth, suggesting that the cilia play an important role in clearing fetal fluid from the lungs. Affected individuals develop recurrent respiratory tract infections. Decreased functioning cilia results in chronic infections like bronchiectasis, otitis media with effusion, chronic rhino-sinusitis, and infertility.Sub fertility or infertility in male PCD patients is caused by sperm dysmotility as the sperm tail is architecturally is analogous to respiratory cilia and powered by dynein motors additionally, due to dyskinetic cilia in their oviducts females with PCD also experience fertility problems. Abnormal ciliary movement of brain ependymal cilia causes hydrocephalus in small animals with PCD. However, patients with PCD may demonstrate mild fetal ventriculomegaly on prenatal ultrasound scans, hydrocephalus is extremely uncommon in humans, except in those with ciliary aplasia.^[2][3][4]

Primary ciliary dyskinesia has an autosomal recessive inheritance. Mutations in DNAI1 and DNAH5 result in Primary Ciliary Dyskinesia.^[5]

Conditions associated with primary ciliary dyskinesia include:

• Bronchiectasis
• Situs inversus totalis/Kartagener syndrome
• Heterotaxy syndrome or situs ambiguous
• Otitis media
• Infertility
• Hydrocephalus

There are no gross features characteristic of primary ciliary dyskinesia.

Histopathological analysis under an electron microscope may show defects in the dynein arms which could be in inner, outer, or both arms. Irrespective of the location it leads to defective cilia which are unable to maintain normal beat and frequency in variety of epithelial surfaces such as respiratory tract, fallopian tubes, sinuses and development of embryonal axis.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Hafsa Ghaffar, M.B.B.S[2]

There are no established causes for Primary ciliary dyskinesia.PCD is related to defects in mucociliary clearance due to abnormal ciliary structure. Mutations in around 46 different genes throughout the genome have been found to be causative. Some of these include DNAH5, CCDC39, DNAI1, CCDC40, DNAH11, ZMYND10, CCDC103, CCDC151 and ARMC4.

There are no established causes for Primary ciliary dyskinesia.

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Template:Atherosclerosis Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Hafsa Ghaffar, M.B.B.S[2]

Primary ciliary dyskinesia must be differentiated from other conditions that cause infertility, sinusitis, otitis media, and rhinitis.

primary ciliary dyskinesia should be differentiated from other diseases that cause rhinosinusitis, otitis media, and infertility.

• Cystic fibrosis
• Alpha1 antitrypsin deficiency
• Allergic bronchopulmonary aspergillosis.
• Foreign body aspiration
• Immunosuppression.^[1][2][3][4]

On the basis [symptom 1], [symptom 2], and [symptom 3], [disease name] must be differentiated from [disease 1], [disease 2], [disease 3], [disease 4], [disease 5], and [disease 6].

Diseases		Clinical manifestations				Para-clinical findings			Gold standard
		Symptoms		Physical examination
						Lab Findings	Imaging
	Age Of Onset	nasal discharge	cough	wheeze	jaundice	Blood levels	Xray chest	CT scan
Cystic fibrosis.	Infancy	+	+	+	–	–	Hyperinflation, Peri bronchial thickening	Not indicated.	Genotyping CFTR gene mutation. Sweat chloride test.
Alpha1-Antitrypsin (AAT) Deficiency	40-50	_	+	+	+	decreased AAT levels	Hyper lucency in lungs.	–	Blood test.
Allergic Broncho pulmonary aspergillosis.	40-50	–	+	+	–	Eosinophilia.	Round mass with air-crescent sign.	Aspergilloma on CT chest.	Sputum analysis. Lung biopsy for fungal culture
Diseases	cough	nasal discharge		wheeze		Lab 1	X-ray	CT scan	Gold standard
Immunodeficiency.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Hafsa Ghaffar, M.B.B.S[2]

Primary ciliary dyskinesia (PCD) is generally documented as etiology of bronchiectasis not only in children or young adults but also in older patients. It is challenging to demonstrate the prevalence of PCD in diverse population with estimates varying between one in 4000 to one in 40,000. PCD is linked with the high levels of consanguinity. Clinical suspicion of PCD is high in these communities, chronic cough and nasal symptoms should rise concern for prompt diagnostic testing.

• The estimated incidence of PCD is approximately 1 per 15,000 births

• PCD is a rare disorder with an estimated prevalence of 1:10,000^[1]. The prevalence of PCD is difficult to determine, primarily because of limitations in diagnostic methods that focus on testing ciliary ultrastructure and function, Because of a lack of appreciation of the cardinal signs and symptoms of infants, there are fewer than 1,000 patients in the United States with the confirmed diagnosis of PCD.

The mortality rate is difficult to interpret in PCD.

151 PCD adults were selected in a recent retrospective study, median age of 25 years longitudinally followed for 7 years. Incidence were concluded with all-cause mortality of 5% and respiratory related mortality of 3.3%. ^[2]

Delay in diagnosis is commonly seen in PCD in spite of symptoms in early life. Median age at diagnosis was 5.3 yrs (IQR 1.2–8.2, range 0–19 yrs), lower in children with situs inversus compared to those without (3.5 versus 5.8 yrs; p<0.001^[3]

The unexplained respiratory distress, rhinitis and situs inversus makes early referral for PCD testing mandatory.^[4]

• There is no racial predilection to PCD

• PCD affects men and women equally.

The majority of PCD cases are reported in ethnic groups with high rates of consanguinity, such as the British Asian population, Amish communities in US and the Voldendam population in Netherlands.^[5]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Hafsa Ghaffar, M.B.B.S[2]

There are no established risk factors for primary ciliary dyskinesia.

There are no established risk factors for primary ciliary dyskinesia. It has genetic inheritance that affects both males and female.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Hafsa Ghaffar, M.B.B.S[2]

The long-term effects of primary ciliary dyskinesia (PCD) are dependent on respiratory symptoms. PCD is not considered to be life-threatening, but persistent lung and airway disease can lead to permanent damage. Recurrent ear infections can lead to hearing loss, which is sometimes permanent, prompt diagnosis and early treatment improve long-term outcomes.

Primary ciliary dyskinesia develops earlier in life, prognosis depends on the severity of associated symptoms. It is usually diagnosed after workup of persistent rhinorrhea, sinusitis, recurrent pneumonia, persistent otitis media, or infertility. Age on onset directly correlates with disease severity and prognosis.

Chronic childhood infections can be very devastating, but the range and severity of clinical symptoms are expansive. Fortunately, by adulthood primary ciliary dyskinesia usually becomes less problematic and many patients may have near-normal lives. However, cross-sectional data imply that spirometry deteriorates in patients over time. Clinical manifestations include chronic upper and lower airway disease resulting from ineffective mucociliary clearance. Males demonstrate infertility secondary to immotile spermatozoa.^[1]

• Prognosis is generally based on early diagnosis and prompt treatment. Regular chest physiotherapy with bronchodilators or spirometry could improve lung function.
• Children should have regular doctor checkups.

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