Primary_Ciliary_Dyskinesia

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Classifications

Harrison's Chapter

Mechanistic Nosology

⚙

Pathophysiology

Ciliary Dysfunction

Defects in the structure and function of motile cilia impair mucociliary clearance.

respiratory ciliated cell CL:0002368 ependymal cell CL:0000065

DNAI1 hgnc:2954 DNAH5 hgnc:2950

cilium movement GO:0003341 cilium assembly GO:0060271 axoneme assembly GO:0035082

Cilia GO:0005929 axoneme GO:0005930 outer dynein arm GO:0036157

respiratory tract epithelium UBERON:0004802 nasal cavity epithelium UBERON:0005384 trachea UBERON:0003126 bronchus UBERON:0002185

Downstream

Impaired Mucociliary Clearance

Show evidence (6 references)

ORPHA:244 SUPPORT

"A rare, genetically heterogeneous, primarily respiratory disorder characterized by chronic upper and lower respiratory tract disease."

Orphanet definition confirms PCD is characterized by ciliary dysfunction leading to chronic respiratory disease.

PMID:19818430 SUPPORT

"Primary ciliary dyskinesia is a genetically inherited syndrome characterized by cilia immotility or dysmotility. Deficiency in mucociliary clearance produces chronic respiratory infections since birth."

The reference confirms that defects in the structure and function of motile cilia impair mucociliary clearance, supporting the statement.

PMID:20525503 SUPPORT

"Ciliary dysfunction may be primary, the result of genetic mutations resulting in abnormal cilia structure, or secondary, the result of environmental, infectious or inflammatory stimuli that disrupt normal motility or coordination."

This reference supports the statement by indicating that primary ciliary dyskinesia results from genetic mutations affecting cilia structure and function, leading to impaired mucociliary clearance.

+ 3 more references

Impaired Mucociliary Clearance

Failure to effectively remove mucus and pathogens from respiratory passages.

mucociliary clearance GO:0120197

respiratory system UBERON:0001004 paranasal sinus UBERON:0001825

Downstream

Chronic Respiratory Infections

Sinusitis

Otitis Media

Show evidence (4 references)

PMID:11376511 SUPPORT

"Failure to keep the airways sterile by MCC results in a host inflammatory response to the persistent microorganisms which, if it becomes chronic, causes damage to the airway wall and upregulation of mucus production manifest clinically as bronchiectasis, sinusitis and otitis."

The literature supports that primary ciliary dyskinesia (PCD) leads to impaired mucociliary clearance, which results in chronic respiratory infections, sinusitis, and otitis media.

PMID:17142159 SUPPORT

"Primary ciliary dyskinesia is an autosomal recessive genetic disease that results in impaired mucociliary clearance causing progressive involvement of the upper and lower respiratory tract, characterized by airway obstruction and recurrent infections of the lungs, middle ear and paranasal sinuses."

The literature supports that primary ciliary dyskinesia leads to impaired mucociliary clearance and downstream chronic respiratory infections, sinusitis, and otitis media.

PMID:15917207 SUPPORT

"Disruption of 9+2 cilia, which move mucus across respiratory epithelia, leads to rhinitis, sinusitis and bronchiectasis."

The literature supports that disruption of motile cilia, as seen in primary ciliary dyskinesia, leads to impaired mucociliary clearance and resultant respiratory conditions such as sinusitis and bronchiectasis.

+ 1 more reference

Situs Inversus

Abnormal placement of internal organs due to ciliary dysfunction during embryonic development.

determination of left/right symmetry GO:0007368 nodal cilium assembly GO:0044458

embryo UBERON:0000922

Show evidence (3 references)

ORPHA:244 SUPPORT

"Approximately half of the patients have an organ laterality defect (situs inversus totalis or situs ambiguus/heterotaxy)."

Orphanet definition confirms that approximately half of PCD patients have laterality defects.

PMID:16036877 PARTIAL

"The normal left-right asymmetry of the body is thought to be due to the beating of the cilia in the embryonic (Hensen's) node. Total immotility of the cilia should therefore result in random asymmetry of the body that is situs inversus in 50% of the cases. It has also been claimed that 50% of..."

The statement is partially supported. The literature confirms that primary ciliary dyskinesia (PCD) can lead to situs inversus due to ciliary dysfunction during embryonic development, and it is claimed that 50% of PCD cases have situs inversus. However, the phrase 'abnormal placement of internal organs' is more general and could include other forms of laterality defects, not just situs inversus.

PMID:36342963 PARTIAL

"Results: Of 559 participants, 286 (51.2%), 215 (38.5%), and 58 (10.4%) were identified as having situs solitus, situs inversustotalis, and situs ambiguus, respectively; heterotaxy, defined as situs ambiguus with complex cardiovascular defects, was present in 14 (2.5%)"

The statement is partially supported. The data shows that 38.5% of PCD cases have situs inversus totalis, which is close to but not exactly 50%. Additionally, there are other laterality defects like situs ambiguus, which are not covered by the statement.

⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.

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Phenotypes

Cardiovascular 2

Situs Inversus Totalis FREQUENT Situs inversus totalis HP:0001696

Show evidence (4 references)

ORPHA:244 PARTIAL

"HP:0001696 | Situs inversus totalis | Occasional (29-5%)"

Orphanet classifies situs inversus totalis as occasional (29-5%), but literature data shows ~38-50% prevalence, supporting FREQUENT.

PMID:16036877 PARTIAL

"Total immotility of the cilia should therefore result in random asymmetry of the body that is situs inversus in 50% of the cases. It has also been claimed that 50% of cases with PCD have situs inversus."

The literature indicates that situs inversus, including situs inversus totalis, occurs in approximately 50% of primary ciliary dyskinesia (PCD) cases. This suggests that it is not merely 'occasional' but rather relatively common in PCD patients.

PMID:36342963 PARTIAL

The data indicates that situs inversus totalis occurs in 38.5% of PCD cases, which is more frequent than 'occasional.'

+ 1 more reference

Abnormal Heart Morphology OCCASIONAL Abnormal heart morphology HP:0001627

Congenital heart defects associated with laterality abnormalities

Show evidence (1 reference)

ORPHA:244 SUPPORT

"HP:0001627 | Abnormal heart morphology | Occasional (29-5%)"

Orphanet phenotype data classifies abnormal heart morphology as occasional (29-5%) in primary ciliary dyskinesia.

Digestive 1

Intestinal Malrotation VERY_RARE Intestinal malrotation HP:0002566

Associated with situs abnormalities

Show evidence (1 reference)

ORPHA:244 SUPPORT

"HP:0002566 | Intestinal malrotation | Very rare (<4-1%)"

Orphanet phenotype data classifies intestinal malrotation as very rare (<4-1%) in primary ciliary dyskinesia.

Ear 5

Chronic Otitis Media FREQUENT Chronic otitis media HP:0000389

Show evidence (3 references)

ORPHA:244 SUPPORT

"HP:0000389 | Chronic otitis media | Frequent (79-30%)"

Orphanet phenotype data classifies chronic otitis media as frequent (79-30%) in primary ciliary dyskinesia.

PMID:29135867 SUPPORT

"All 15 patients showed ciliary ultrastructural abnormalities on electron microscopy and/or biallelic mutations in genes associated with ciliary function or structure. All 30 eardrums examined showed certain abnormalities. Fourteen patients had otitis media with effusion or its sequelae. The..."

The study found that patients with primary ciliary dyskinesia (PCD) frequently exhibited otologic issues, including chronic otitis media.

PMID:19796826 SUPPORT

"Primary ciliary dyskinesia is an autosomal recessively inherited group of disorders of ciliary ultrastructure. Otolaryngologists are frequently involved in the management of some of the most common symptoms of primary ciliary dyskinesia including chronic rhinitis, sinusitis and otitis media with..."

This reference supports that chronic otitis media and other otologic issues are common in patients with primary ciliary dyskinesia.

Hearing Loss OCCASIONAL Hearing impairment HP:0000365

Show evidence (4 references)

ORPHA:244 SUPPORT

"HP:0000365 | Hearing impairment | Occasional (29-5%)"

Orphanet phenotype data classifies hearing impairment as occasional (29-5%) in primary ciliary dyskinesia.

PMID:29287859 REFUTE

"Slight to mild CHL and all types of otitis media are prevalent among patients with PCD, and some of these children have sensorineural hearing loss (SNHL)."

The study indicates that hearing loss is a prevalent condition among patients with primary ciliary dyskinesia (PCD), not occasional.

PMID:9222635 REFUTE

"All children (11 patients) had bilateral otitis media with effusion. Of the five adults, three had tympanosclerosis; one had bilateral cholesteatoma; and one patient had bilateral keratosis obturans in combination with tympanosclerosis."

The study describes otological manifestations including hearing loss as a prominent feature in patients with PCD, suggesting it is not occasional but rather common.

+ 1 more reference

Otitis Media FREQUENT Otitis media HP:0000388

Recurrent Otitis Media FREQUENT Recurrent otitis media HP:0000403

Show evidence (1 reference)

ORPHA:244 SUPPORT

"HP:0000403 | Recurrent otitis media | Frequent (79-30%)"

Orphanet phenotype data classifies recurrent otitis media as frequent (79-30%) in primary ciliary dyskinesia.

Conductive Hearing Impairment OCCASIONAL Conductive hearing impairment HP:0000405

Show evidence (1 reference)

ORPHA:244 SUPPORT

"HP:0000405 | Conductive hearing impairment | Occasional (29-5%)"

Orphanet phenotype data classifies conductive hearing impairment as occasional (29-5%) in primary ciliary dyskinesia.

Genitourinary 2

Male Infertility FREQUENT Male infertility HP:0003251

Due to sperm flagellar defects affecting motility

Show evidence (1 reference)

ORPHA:244 SUPPORT

"HP:0003251 | Male infertility | Frequent (79-30%)"

Orphanet phenotype data classifies male infertility as frequent (79-30%) in primary ciliary dyskinesia.

Female Infertility OCCASIONAL Female infertility HP:0008222

Due to impaired ciliary function in fallopian tubes

Show evidence (1 reference)

ORPHA:244 SUPPORT

"HP:0008222 | Female infertility | Occasional (29-5%)"

Orphanet phenotype data classifies female infertility as occasional (29-5%) in primary ciliary dyskinesia.

Head and Neck 4

Nasal Polyposis FREQUENT Nasal polyposis HP:0100582

Show evidence (3 references)

ORPHA:244 SUPPORT

"HP:0100582 | Nasal polyposis | Frequent (79-30%)"

Orphanet phenotype data classifies nasal polyposis as frequent (79-30%) in primary ciliary dyskinesia.

PMID:37997295 NO_EVIDENCE

"Despite endoscopic differences, PCD-CRS and cystic fibrosis-related chronic rhinosinusitis (CF-CRS) had similar structured histopathology reports. Compared to healthy patients and those with idiopathic chronic rhinosinusitis without nasal polyps, patients with PCD-CRS had an increased neutrophil count."

The abstract discusses histopathology and neutrophil count in PCD-CRS, but does not provide evidence on the frequency of nasal polyps in PCD.

PMID:39069333 NO_EVIDENCE

"This review article explores the respiratory aspects of primary ciliary dyskinesia (PCD), a rare, heterogenous, genetic disorder characterized by impaired motile ciliary function. It discusses the clinical diagnosis and management strategies for PCD-related respiratory disease, including chronic..."

The review focuses on respiratory aspects of PCD and does not mention nasal polyps as a frequent gastrointestinal manifestation.

Sinusitis FREQUENT Sinusitis HP:0000246

Chronic Rhinosinusitis FREQUENT Chronic sinusitis HP:0011109

Chronic inflammation of nasal passages and sinuses

Show evidence (1 reference)

ORPHA:244 SUPPORT

"HP:0011109 | Chronic sinusitis | Frequent (79-30%)"

Orphanet phenotype data classifies chronic sinusitis as frequent (79-30%) in primary ciliary dyskinesia.

Nasal Congestion FREQUENT Nasal congestion HP:0001742

Show evidence (1 reference)

ORPHA:244 SUPPORT

"HP:0001742 | Nasal congestion | Frequent (79-30%)"

Orphanet phenotype data classifies nasal congestion as frequent (79-30%) in primary ciliary dyskinesia.

Immune 2

Recurrent Respiratory Infections VERY_FREQUENT Recurrent respiratory infections HP:0002205

Show evidence (4 references)

PMID:39069333 SUPPORT

The article discusses recurrent respiratory diseases as a significant aspect of PCD, supporting the statement that recurrent respiratory infections are very frequent in PCD.

PMID:36214320 SUPPORT

"Ninety-two children with chronic respiratory symptoms were divided into 4 groups: 18 children with refractory asthma, 10 with bronchiectasis without dextrocardia, 18 with dextrocardia and 46 with recurrent respiratory tract infections."

The study highlights recurrent respiratory tract infections in children with chronic respiratory symptoms, supporting the statement that recurrent respiratory infections are very frequent in PCD.

PMID:31430425 SUPPORT

"The objective of this study was to evaluate the prevalence of chronic rhinosinusitis (CRS) and its characteristics in bronchiectasis patients suspected of harboring ciliary dyskinesia."

The study mentions chronic rhinosinusitis and bronchiectasis in patients suspected of ciliary dyskinesia, indicating frequent respiratory issues.

+ 1 more reference

Chronic Respiratory Infections FREQUENT Recurrent respiratory infections HP:0002205

Limbs 1

Digital Clubbing OCCASIONAL Clubbing HP:0001217

Show evidence (1 reference)

ORPHA:244 SUPPORT

"HP:0001217 | Clubbing | Occasional (29-5%)"

Orphanet phenotype data classifies digital clubbing as occasional (29-5%) in primary ciliary dyskinesia.

Nervous System 1

Hydrocephalus VERY_RARE Hydrocephalus HP:0000238

Related to ependymal ciliary dysfunction

Show evidence (1 reference)

ORPHA:244 SUPPORT

"HP:0000238 | Hydrocephalus | Very rare (<4-1%)"

Orphanet phenotype data classifies hydrocephalus as very rare (<4-1%) in primary ciliary dyskinesia.

Respiratory 7

Chronic Cough VERY_FREQUENT Chronic cough HP:0034315

Show evidence (2 references)

PMID:27258773 SUPPORT

"Primary ciliary dyskinesia (PCD) is a rare, heterogeneous, recessive, genetic disorder of motile cilia, leading to chronic upper and lower respiratory symptoms."

The statement is supported because PCD leads to chronic respiratory symptoms, including chronic cough.

PMID:17142159 SUPPORT

The statement is supported because PCD causes progressive involvement of the respiratory tract, which includes chronic cough.

Bronchiectasis FREQUENT Bronchiectasis HP:0002110

Show evidence (10 references)

ORPHA:244 PARTIAL

"HP:0002110 | Bronchiectasis | Occasional (29-5%)"

Orphanet classifies bronchiectasis as occasional (29-5%), likely reflecting cross-sectional point prevalence rather than cumulative incidence; multiple PMIDs describe it as a defining long-term complication of PCD.

PMID:10894096 SUPPORT

"Patients with primary ciliary dyskinesia could potentially develop recurrent sinotrachrobronchitis, bronchiectasis, serous otitis media, hydrocephalus, and male infertility."

The article mentions bronchiectasis as one of the potential conditions that patients with PCD could develop.

PMID:36344229 SUPPORT

"Typical manifestations include bronchiectasis, secretory otitis media, sinusitis, situs inversus, and infertility."

The article lists bronchiectasis as a typical manifestation of primary ciliary dyskinesia.

+ 7 more references

Neonatal Respiratory Distress FREQUENT Neonatal respiratory distress HP:0002643

Common presenting feature in newborns with PCD

Show evidence (2 references)

ORPHA:244 SUPPORT

"HP:0002643 | Neonatal respiratory distress | Frequent (79-30%)"

Orphanet phenotype data classifies neonatal respiratory distress as frequent (79-30%) in primary ciliary dyskinesia.

PMID:19720631 SUPPORT

"73% had a history of neonatal respiratory distress."

In a consanguineous British Asian PCD cohort, 73% of patients had neonatal respiratory distress.

Productive Cough FREQUENT Productive cough HP:0031245

Show evidence (1 reference)

ORPHA:244 SUPPORT

"HP:0031245 | Productive cough | Frequent (79-30%)"

Orphanet phenotype data classifies productive cough as frequent (79-30%) in primary ciliary dyskinesia.

Wheezing OCCASIONAL Wheezing HP:0030828

Show evidence (1 reference)

ORPHA:244 SUPPORT

"HP:0030828 | Wheezing | Occasional (29-5%)"

Orphanet phenotype data classifies wheezing as occasional (29-5%) in primary ciliary dyskinesia.

Atelectasis OCCASIONAL Atelectasis HP:0100750

Show evidence (1 reference)

ORPHA:244 SUPPORT

"HP:0100750 | Atelectasis | Occasional (29-5%)"

Orphanet phenotype data classifies atelectasis as occasional (29-5%) in primary ciliary dyskinesia.

Respiratory Failure VERY_RARE Respiratory failure HP:0002878

Show evidence (1 reference)

ORPHA:244 SUPPORT

"HP:0002878 | Respiratory failure | Very rare (<4-1%)"

Orphanet phenotype data classifies respiratory failure as very rare (<4-1%) in primary ciliary dyskinesia.

Other 5

Recurrent Sinopulmonary Infections FREQUENT Recurrent sinopulmonary infections HP:0005425

Show evidence (1 reference)

ORPHA:244 SUPPORT

"HP:0005425 | Recurrent sinopulmonary infections | Frequent (79-30%)"

Orphanet phenotype data classifies recurrent sinopulmonary infections as frequent (79-30%) in primary ciliary dyskinesia.

Chronic Rhinitis FREQUENT Chronic rhinitis HP:0002257

Show evidence (1 reference)

ORPHA:244 SUPPORT

"HP:0002257 | Chronic rhinitis | Frequent (79-30%)"

Orphanet phenotype data classifies chronic rhinitis as frequent (79-30%) in primary ciliary dyskinesia.

Abnormal Sputum FREQUENT Abnormal sputum HP:0032016

Show evidence (1 reference)

ORPHA:244 SUPPORT

"HP:0032016 | Abnormal sputum | Frequent (79-30%)"

Orphanet phenotype data classifies abnormal sputum as frequent (79-30%) in primary ciliary dyskinesia.

Abnormal Sperm Motility FREQUENT Abnormal sperm motility HP:0012206

Show evidence (1 reference)

ORPHA:244 SUPPORT

"HP:0012206 | Abnormal sperm motility | Frequent (79-30%)"

Orphanet phenotype data classifies abnormal sperm motility as frequent (79-30%) in primary ciliary dyskinesia.

Airway Obstruction OCCASIONAL Airway obstruction HP:0006536

Show evidence (1 reference)

ORPHA:244 SUPPORT

"HP:0006536 | Airway obstruction | Occasional (29-5%)"

Orphanet phenotype data classifies airway obstruction as occasional (29-5%) in primary ciliary dyskinesia.

🧬

Genetic Associations

DNAI1 (Pathogenic Variants)

Show evidence (5 references)

ORPHA:244 SUPPORT

"DNAI1 | dynein axonemal intermediate chain 1 | hgnc:2954 | Disease-causing germline mutation(s) in"

Orphanet gene-disease association data confirms DNAI1 as a disease-causing gene for primary ciliary dyskinesia.

PMID:11893720 SUPPORT

"Mutations in DNAI1 (IC78) cause primary ciliary dyskinesia."

This study directly links mutations in DNAI1 to the cause of primary ciliary dyskinesia.

PMID:35869935 SUPPORT

"13 rare variants were identified in patients with PCD, among which were three homozygous causative variants (including one splicing variant) in the PCD-associated genes CCDC40 and DNAI1."

The study identifies causative variants in DNAI1 associated with primary ciliary dyskinesia.

+ 2 more references

DNAH5 (Pathogenic Variants)

Show evidence (3 references)

ORPHA:244 SUPPORT

"DNAH5 | dynein axonemal heavy chain 5 | hgnc:2950 | Disease-causing germline mutation(s) in"

Orphanet gene-disease association data confirms DNAH5 as a disease-causing gene for primary ciliary dyskinesia.

PMID:31118369 SUPPORT

"A genetic examination detected compound heterozygous mutations of DNAH5 that encode ODA components."

The study reports a case of primary ciliary dyskinesia (PCD) with DNAH5 mutations, confirming the association between PCD and pathogenic variants in DNAH5.

PMID:36727596 SUPPORT

"Most PCD-causing variants result in abnormal outer dynein arms (ODAs), which provide the generative force for respiratory ciliary beating and proper mucociliary clearance."

The study indicates that pathogenic variants causing PCD often result in abnormal ODAs, which are associated with DNAH5.

DNAH11 (Pathogenic Variants)

Show evidence (1 reference)

ORPHA:244 SUPPORT

"DNAH11 | dynein axonemal heavy chain 11 | hgnc:2942 | Disease-causing germline mutation(s) in"

Orphanet gene-disease association data confirms DNAH11 as a disease-causing gene for primary ciliary dyskinesia.

CCDC39 (Pathogenic Variants)

Show evidence (1 reference)

ORPHA:244 SUPPORT

"CCDC39 | coiled-coil domain 39 molecular ruler complex subunit | hgnc:25244 | Disease-causing germline mutation(s) in"

Orphanet gene-disease association data confirms CCDC39 as a disease-causing gene for primary ciliary dyskinesia.

CCDC40 (Pathogenic Variants)

Show evidence (1 reference)

ORPHA:244 SUPPORT

"CCDC40 | coiled-coil domain 40 molecular ruler complex subunit | hgnc:26090 | Disease-causing germline mutation(s) in"

Orphanet gene-disease association data confirms CCDC40 as a disease-causing gene for primary ciliary dyskinesia.

RSPH1 (Pathogenic Variants)

Show evidence (1 reference)

ORPHA:244 SUPPORT

"RSPH1 | radial spoke head component 1 | hgnc:12371 | Disease-causing germline mutation(s) (loss of function) in"

Orphanet gene-disease association data confirms RSPH1 as a disease-causing gene for primary ciliary dyskinesia.

RSPH4A (Pathogenic Variants)

Show evidence (1 reference)

ORPHA:244 SUPPORT

"RSPH4A | radial spoke head component 4A | hgnc:21558 | Disease-causing germline mutation(s) in"

Orphanet gene-disease association data confirms RSPH4A as a disease-causing gene for primary ciliary dyskinesia.

RSPH9 (Pathogenic Variants)

Show evidence (1 reference)

ORPHA:244 SUPPORT

"RSPH9 | radial spoke head component 9 | hgnc:21057 | Disease-causing germline mutation(s) in"

Orphanet gene-disease association data confirms RSPH9 as a disease-causing gene for primary ciliary dyskinesia.

CCNO (Pathogenic Variants)

Show evidence (1 reference)

ORPHA:244 SUPPORT

"CCNO | cyclin O | hgnc:18576 | Disease-causing germline mutation(s) (loss of function) in"

Orphanet gene-disease association data confirms CCNO as a disease-causing gene for primary ciliary dyskinesia.

FOXJ1 (Pathogenic Variants)

Show evidence (1 reference)

ORPHA:244 SUPPORT

"FOXJ1 | forkhead box J1 | hgnc:3816 | Disease-causing germline mutation(s) (loss of function) in"

Orphanet gene-disease association data confirms FOXJ1 as a disease-causing gene for primary ciliary dyskinesia.

MCIDAS (Pathogenic Variants)

Show evidence (1 reference)

ORPHA:244 SUPPORT

"MCIDAS | multiciliate differentiation and DNA synthesis associated cell cycle protein | hgnc:40050 | Disease-causing germline mutation(s) (loss of function) in"

Orphanet gene-disease association data confirms MCIDAS as a disease-causing gene for primary ciliary dyskinesia.

ODAD1 (Pathogenic Variants)

Show evidence (1 reference)

ORPHA:244 SUPPORT

"ODAD1 | outer dynein arm docking complex subunit 1 | hgnc:26560 | Disease-causing germline mutation(s) (loss of function) in"

Orphanet gene-disease association data confirms ODAD1 as a disease-causing gene for primary ciliary dyskinesia.

CFAP221 (Pathogenic Variants)

Gene: CFAP221 hgnc:33720

Show evidence (1 reference)

CGGV:assertion_c7c841e5-2973-4f23-8603-970e9e2cbc92-2025-12-16T120000.000Z SUPPORT Other

ClinGen classifies the CFAP221-primary ciliary dyskinesia gene-disease relationship as definitive with autosomal recessive inheritance.

CFAP46 (Pathogenic Variants)

Gene: CFAP46 hgnc:25247

Show evidence (1 reference)

CGGV:assertion_eabe809a-1203-4d42-9052-21f39717754f-2025-10-17T160000.000Z SUPPORT Other

ClinGen classifies the CFAP46-primary ciliary dyskinesia gene-disease relationship as limited with autosomal recessive inheritance.

CFAP57 (Pathogenic Variants)

Gene: CFAP57 hgnc:26485

Show evidence (1 reference)

CGGV:assertion_50ed292f-0044-4c82-9419-a040cbcaf205-2022-06-23T160000.000Z SUPPORT Other

ClinGen classifies the CFAP57-primary ciliary dyskinesia gene-disease relationship as limited with autosomal recessive inheritance.

DAW1 (Pathogenic Variants)

Gene: DAW1 hgnc:26383

Show evidence (1 reference)

CGGV:assertion_8610990f-63cf-466a-8cd7-fbf7ae58d0f2-2024-06-13T160000.000Z SUPPORT Other

ClinGen classifies the DAW1-primary ciliary dyskinesia gene-disease relationship as limited with autosomal recessive inheritance.

DNAH1 (Pathogenic Variants)

Gene: DNAH1 hgnc:2940

Show evidence (1 reference)

CGGV:assertion_a07c8b6e-a558-498b-975c-b12e96878a44-2025-10-16T160000.000Z SUPPORT Other

ClinGen classifies the DNAH1-primary ciliary dyskinesia gene-disease relationship as limited with autosomal recessive inheritance.

DNAH10 (Pathogenic Variants)

Gene: DNAH10 hgnc:2941

Show evidence (1 reference)

CGGV:assertion_698c6b23-a6fb-4b56-a38e-b29d5f8bbd86-2025-02-13T170000.000Z SUPPORT Other

ClinGen classifies the DNAH10-primary ciliary dyskinesia gene-disease relationship as limited with autosomal recessive inheritance.

DNAH7 (Pathogenic Variants)

Gene: DNAH7 hgnc:18661

Show evidence (1 reference)

CGGV:assertion_90a097d6-5127-4466-8c81-00e99dab2696-2025-02-13T170000.000Z SUPPORT Other

ClinGen classifies the DNAH7-primary ciliary dyskinesia gene-disease relationship as limited with autosomal recessive inheritance.

NME8 (Pathogenic Variants)

Gene: NME8 hgnc:16473

Show evidence (1 reference)

CGGV:assertion_57ca8383-55b6-4edd-9be2-67b1c5142ed1-2023-06-08T160000.000Z SUPPORT Other

ClinGen classifies the NME8-primary ciliary dyskinesia gene-disease relationship as limited with autosomal recessive inheritance.

SPEF2 (Pathogenic Variants)

Gene: SPEF2 hgnc:26293

Show evidence (1 reference)

CGGV:assertion_e137eed5-fcd8-4497-a6dc-6651062d1cf3-2025-01-09T170000.000Z SUPPORT Other

ClinGen classifies the SPEF2-primary ciliary dyskinesia gene-disease relationship as definitive with autosomal recessive inheritance.

💊

Medical Actions

Airway Clearance Techniques

Action: physical therapy MAXO:0000011

Methods to help clear mucus from the lungs, such as chest physical therapy.

Show evidence (3 references)

PMID:28408202 SUPPORT

"Airway clearance techniques (ACTs) are commonly recommended for patients with PCD to facilitate mucus clearance, despite a lack of evidence in this group."

The reference acknowledges the use of airway clearance techniques in patients with Primary Ciliary Dyskinesia (PCD) to help clear mucus from the lungs.

PMID:38861625 SUPPORT

"Airway clearance techniques (ACTs) are critical in managing respiratory conditions characterized by mucus hypersecretion and impaired clearance, such as cystic fibrosis, chronic obstructive pulmonary disease (COPD), and various neuromuscular disorders."

The reference discusses the importance of ACTs in managing conditions with mucus hypersecretion and impaired clearance, which aligns with the use of these techniques in PCD.

PMID:11376511 SUPPORT

"There are three principal disorders of MCC. Firstly, primary ciliary dyskinesia (PCD)..."

The reference mentions PCD and discusses airway hygiene and mucociliary clearance, supporting the relevance of airway clearance techniques in PCD.

Antibiotic Therapy

Action: antibiotic therapy Ontology label: Antibiotic Therapy NCIT:C15620

Long-term or prophylactic antibiotics to control respiratory infections.

Target Phenotypes: Recurrent Respiratory Infections HP:0002205

Show evidence (3 references)

PMID:28552099 SUPPORT

"Non-functional airway cilia impair the mucociliary clearance (MCC), causing mucostasis, lung infections and destruction, chronic rhinosinusitis (CRS) and hearing impairment. It is of paramount importance to postpone chronic lung infection mainly with Gram-negative bacteria (GNB) in patients with..."

The literature mentions the importance of postponing chronic lung infection in patients with impaired MCC, which is a characteristic of PCD. This aligns with the use of long-term antibiotic therapy to manage such infections.

PMID:26586601 SUPPORT

"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..."

The reference states that antibiotic treatment for pulmonary exacerbation is a mainstay of therapy for PCD, supporting the use of long-term or prophylactic antibiotics.

PMID:19812481 SUPPORT

"Antibiotic prophylaxis is one of the mainstays of therapy of primary immunodeficiencies."

While the focus is on primary immunodeficiencies, the principle of using antibiotic prophylaxis can be extended to PCD due to similar needs for managing chronic infections.

Bronchodilators

Action: bronchodilator therapy MAXO:0000316

Medications to help open airways and ease breathing.

Show evidence (4 references)

PMID:36639347 NO_EVIDENCE

The reference discusses new data and future challenges related to Primary Ciliary Dyskinesia (PCD) and bronchiectasis but does not provide specific information about the use of bronchodilators for PCD.

PMID:39269762 NO_EVIDENCE

"Primary ciliary dyskinesia (PCD) is a respiratory disorder that impairs mucociliary clearance, leading to decreased lung function."

The reference focuses on airway clearance techniques in PCD and does not mention the use of bronchodilators.

PMID:33507585 NO_EVIDENCE

The reference discusses intrapulmonary percussive ventilation for PCD but does not mention bronchodilators.

+ 1 more reference

Nasal Steroids

Action: Pharmacotherapy NCIT:C15986

Used to treat nasal polyps and chronic sinusitis.

Show evidence (4 references)

PMID:19879441 PARTIAL

"Long-term treatment with corticosteroid nasal spray reduces inflammation and nasal polyp size, and improves nasal symptoms such as nasal blockage, rhinorrea, and the loss of smell."

While nasal steroids are used to treat nasal polyps and chronic rhinosinusitis, the statement should specify that they are used to manage symptoms rather than being a description of Primary Ciliary Dyskinesia (PCD).

PMID:33305974 PARTIAL

"Topical nasal steroids play an important role in the treatment of CRS."

Nasal steroids are used in the treatment of chronic rhinosinusitis (CRS), which can be a condition associated with PCD. However, the statement should clarify that nasal steroids are for symptom management rather than a direct description of PCD.

PMID:35312075 PARTIAL

"Our findings indicate for the first time that PCD patients with CRSwNP display a more severe disease than those with CRSsNP."

This reference indicates that chronic rhinosinusitis with nasal polyps (CRSwNP) is more severe in PCD patients. However, it does not directly state that nasal steroids are used to treat these conditions in the context of PCD.

+ 1 more reference

Hearing Aids

Action: supportive care MAXO:0000950

Assistive devices for hearing loss management.

Show evidence (5 references)

PMID:29287859 NO_EVIDENCE

"CONCLUSIONS: Slight to mild CHL and all types of otitis media are prevalent among patients with PCD, and some of these children have sensorineural hearing loss (SNHL)."

The study discusses the prevalence and types of hearing loss in children with PCD but does not mention the use of hearing aids or other assistive devices for management.

PMID:22960754 NO_EVIDENCE

"This article explores factors pertaining to children's use of and attitudes toward hearing technologies, such as hearing aids, cochlear implants, teacher-worn microphones, and student-worn microphones."

This study focuses on the use of hearing technologies among students with hearing impairment but does not specifically address children with PCD.

PMID:28187057 NO_EVIDENCE

"OBJECTIVE: To evaluate whether wearing auditory assistive devices can improve gait and dynamic balance."

The study evaluates the impact of hearing assistive devices on gait and balance in adults but does not mention their use in patients with PCD.

+ 2 more references

Genetic Counseling

Action: genetic counseling MAXO:0000079

Provides information and support for affected individuals and families.

Show evidence (4 references)

PMID:29800551 NO_EVIDENCE

"Our knowledge of cilia genetics and the function of the proteins encoded has led to a greater understanding of the clinical manifestations of motile ciliopathies. These advances have changed our approach toward diagnostic testing for primary ciliary dyskinesia."

The reference discusses advances in genetics and diagnostic testing for primary ciliary dyskinesia but does not mention genetic counseling providing information and support for affected individuals and families.

PMID:29905515 NO_EVIDENCE

"This document presents the American Thoracic Society clinical practice guidelines for the diagnosis of primary ciliary dyskinesia (PCD)."

The guideline focuses on diagnostic practices and does not mention genetic counseling or support for affected individuals and families.

PMID:19410203 NO_EVIDENCE

"Newer genetic modifiers show an exciting potential for personalized medication, combining selection of patients with a common genetic mutation and a drug treatment that has been specifically designed to overcome that mutation, and will greatly enhance the therapeutic arsenal for PCD."

The reference discusses potential future therapies for PCD but does not mention genetic counseling or support services.

+ 1 more reference

🌍

Environmental Factors

Air Pollution

Show evidence (2 references)

PMID:34574829 SUPPORT

"Air pollution decreases quality of life and life expectancy. It exacerbates acute and chronic respiratory symptoms in patients with chronic airway diseases, and increases the morbidity and risk of hospitalization associated with respiratory diseases."

The literature indicates that air pollution exacerbates respiratory symptoms in patients with chronic airway diseases, which can be inferred to include conditions like Primary Ciliary Dyskinesia (PCD).

PMID:37147124 SUPPORT

"CONCLUSIONS: Short-term ambient NO2 and PM2.5 exposure were associated with increased odds of exacerbations in Canadians with mild to moderate COPD, further heightening the awareness of non-infectious triggers of COPD exacerbations"

While this study focuses on COPD, it highlights the role of air pollution in exacerbating respiratory conditions, which can be extended to other chronic respiratory diseases like PCD.

🔬

Biochemical Markers

Nitric Oxide (Decreased)

Context: Lower levels in nasal and exhaled breath

Show evidence (6 references)

PMID:12511725 SUPPORT

"Low values in both eNO and nNO readings (<2.4 ppb and <187 ppb, respectively) identified PCD patients from other bronchiectatic patients with a specificity of 98% and a positive predictive value of 92%."

This study shows that both exhaled nitric oxide (eNO) and nasal nitric oxide (nNO) levels are significantly lower in patients with primary ciliary dyskinesia (PCD) compared to other groups.

PMID:22408195 SUPPORT

"Despite chronic infections, nasal nitric oxide in such patients is markedly reduced and is used as a screening test for this condition."

This abstract confirms that nasal nitric oxide levels are significantly reduced in PCD patients.

PMID:31770003 SUPPORT

"Nasal nitric oxide concentrations are extremely low in primary ciliary dyskinesia (PCD), and measurement of this nasal gas is recommended as a PCD diagnostic test in cooperative patients aged 5 years and older."

This paper supports the statement by indicating that nasal nitric oxide levels are extremely low in PCD patients.

+ 3 more references

🧫

Experimental Models

Patient-derived nasal epithelial air-liquid interface model PRIMARY_CELL_CULTURE namo:TwoDCellCulture

Expanded basal epithelial cells from nasal brush biopsies re-differentiated in miniaturized air-liquid interface cultures to preserve genotype-linked ciliary ultrastructural and motility defects in primary ciliary dyskinesia.

Organism

human NCBITaxon:9606

Tissue

nasal cavity epithelium UBERON:0005384

Cell source

Patient-derived nasal basal epithelial cells expanded from nasal brush biopsies

Culture

Miniaturized 96-well Transwell air-liquid interface culture

Publication

PMID:33795320

Findings

Patient-derived nasal ALI cultures retain genotype-linked ciliary ultrastructural and motility defects and can be used to test rescue strategies for reduced multiciliogenesis

Show evidence (2 references)

PMID:33795320 SUPPORT In Vitro

"Initial analyses of ciliary ultrastructure, beat pattern and beat frequency in the 96-well transwell format ALI cultures indicate that a range of different PCD defects can be retained in these cultures."

Supports use of expanded nasal ALI cultures as a disease-relevant PCD model that preserves mutation-associated ciliary defects.

PMID:33795320 SUPPORT In Vitro

"As proof-of-principle, we performed a personalised investigation in a patient with a rare and severe form of PCD (reduced generation of motile cilia), in this case caused by a homozygous nonsense mutation in the MCIDAS gene."

Links the ALI model to a mechanistically relevant multiciliogenesis defect within a defined PCD genotype.

Show evidence (1 reference)

PMID:33795320 SUPPORT In Vitro

"Primary cell culture of basal epithelial cells from nasal brush biopsies followed by ciliated differentiation at the air-liquid interface (ALI) has proven to be a useful tool in PCD diagnostics but the technique's broader utility, including in pre-clinical PCD research, has been restricted by..."

Establishes patient-derived nasal ALI culture as an existing PCD modeling system and motivates the expanded higher-throughput format.

Patient-derived airway organoid model ORGANOID namo:Organoid

Airway organoids established from nasal inferior turbinate brush samples and differentiated toward ciliated cells to capture patient-specific ciliary beating abnormalities in primary ciliary dyskinesia.

Organism

human NCBITaxon:9606

Tissue

nasal cavity epithelium UBERON:0005384

Cell source

Patient-derived nasal inferior turbinate epithelial cells expanded as airway organoids

Culture

Long-term expandable airway organoid culture with ciliated differentiation

Publication

PMID:34693619

Findings

Patient-derived airway organoids reproduce mutation-linked differences in ciliary beating and support genotype-specific functional interrogation

Show evidence (2 references)

PMID:34693619 SUPPORT In Vitro

"Patient-specific differences in ciliary beating are observed and are in agreement with the patients' genetic mutations."

Supports the organoid model as a genotype-resolved readout of the ciliary dysfunction central to PCD.

PMID:34693619 SUPPORT In Vitro

"More detailed organoid ciliary phenotypes can thus be documented in addition to the standard diagnostic procedure."

Supports use of organoids for mechanistically richer ciliary phenotyping in PCD.

Show evidence (1 reference)

PMID:34693619 SUPPORT In Vitro

"We apply this condition to AOs established from nasal inferior turbinate brush samples of patients suffering from primary ciliary dyskinesia (PCD), a pulmonary disease caused by dysfunction of the motile cilia in the airways."

Establishes patient-derived airway organoids as a directly disease-relevant non-animal model for PCD.

Patient-specific hiPSC-derived airway epithelium model IPSC_DERIVED_MODEL namo:TwoDCellCulture

Human induced pluripotent stem cell-derived airway epithelium differentiated at air-liquid interface to model structural ciliary defects and impaired mucociliary transport in genetically defined primary ciliary dyskinesia.

Organism

human NCBITaxon:9606

Tissue

respiratory airway UBERON:0001005

Cell source

Patient-specific induced pluripotent stem cell lines differentiated into ciliated airway epithelium

Culture

Air-liquid interface differentiation of hiPSC-derived airway epithelium

Publication

PMID:37296588

Findings

Patient-specific hiPSC-derived airway epithelium reproduces molecular, ultrastructural, and functional ciliary defects, including impaired mucociliary transport

Show evidence (1 reference)

PMID:37296588 SUPPORT In Vitro

"Applying transmission electron microscopy, immunofluorescence staining, ciliary beat frequency, and mucociliary transport measurements, we could demonstrate that ciliated respiratory epithelia cells derived from two PCD patient-specific hiPSC lines carrying mutations in DNAH5 and NME5,..."

Shows that hiPSC-derived airway epithelium reproduces the molecular and functional consequences of PCD mutations, including impaired transport.

Show evidence (2 references)

PMID:37296588 SUPPORT In Vitro

"Here, we developed an in vitro model for PCD based on human induced pluripotent stem cell (hiPSC)-derived airway epithelium in Air-Liquid-Interface cultures."

Establishes hiPSC-derived airway epithelium as a PCD-specific in vitro model.

PMID:37296588 SUPPORT In Vitro

"Motile cilia dysfunction results in diminished mucociliary clearance (MCC) of pathogens in the respiratory tract and chronic airway inflammation and infections successively causing progressive lung damage."

Connects the model's mucociliary transport readouts to the central airway pathophysiology of PCD.

{ }

Source YAML

click to show

name: Primary_Ciliary_Dyskinesia
creation_date: '2025-12-04T16:57:31Z'
updated_date: '2026-04-28T12:00:00Z'
category: Genetic
parents:
- Ciliopathy
- Respiratory Disease
prevalence:
- population: Europe
  subtype: Prevalence at birth
  percentage: 0.001-0.01
  evidence:
  - reference: ORPHA:244
    supports: SUPPORT
    snippet: "1-9 / 100 000 | Europe | Prevalence at birth | PMID:23871404"
    explanation: Orphanet epidemiology data reports prevalence at birth in Europe of 1-9 per 100,000.
  - reference: PMID:23871404
    supports: SUPPORT
    snippet: "Prevalence, about 1/15,000 to 1/30,000, is probably underestimated, as diagnosis might not be evocated in absence of Kartagener syndrome."
    explanation: French review estimates prevalence at 1/15,000 to 1/30,000, consistent with the Orphanet range of 1-9 per 100,000.
- population: Pakistan (British Asian)
  subtype: Point prevalence
  percentage: 0.01-0.05
  evidence:
  - reference: ORPHA:244
    supports: SUPPORT
    snippet: "1-5 / 10 000 | Pakistan | Point prevalence | PMID:19720631"
    explanation: Orphanet epidemiology data reports point prevalence in Pakistan of 1-5 per 10,000.
  - reference: PMID:19720631
    supports: SUPPORT
    snippet: "The prevalence of PCD in the population studied was one in 2265."
    explanation: High prevalence in a consanguineous British Asian population from Bradford, UK, consistent with the Orphanet range.
pathophysiology:
- name: Ciliary Dysfunction
  conforms_to: "ciliopathy_dysfunction#Motile Cilia Beat Dysfunction"
  description: Defects in the structure and function of motile cilia impair mucociliary clearance.
  genes:
  - preferred_term: DNAI1
    term:
      id: hgnc:2954
      label: DNAI1
  - preferred_term: DNAH5
    term:
      id: hgnc:2950
      label: DNAH5
  cell_types:
  - preferred_term: respiratory ciliated cell
    term:
      id: CL:0002368
      label: respiratory tract epithelial cell
  - preferred_term: ependymal cell
    term:
      id: CL:0000065
      label: ependymal cell
  biological_processes:
  - preferred_term: cilium movement
    term:
      id: GO:0003341
      label: cilium movement
  - preferred_term: cilium assembly
    term:
      id: GO:0060271
      label: cilium assembly
  - preferred_term: axoneme assembly
    term:
      id: GO:0035082
      label: axoneme assembly
  locations:
  - preferred_term: respiratory tract epithelium
    term:
      id: UBERON:0004802
      label: respiratory tract epithelium
  - preferred_term: nasal cavity epithelium
    term:
      id: UBERON:0005384
      label: nasal cavity epithelium
  - preferred_term: trachea
    term:
      id: UBERON:0003126
      label: trachea
  - preferred_term: bronchus
    term:
      id: UBERON:0002185
      label: bronchus
  cellular_components:
  - preferred_term: Cilia
    term:
      id: GO:0005929
      label: cilium
  - preferred_term: axoneme
    term:
      id: GO:0005930
      label: axoneme
  - preferred_term: outer dynein arm
    term:
      id: GO:0036157
      label: outer dynein arm
  downstream:
  - target: Impaired Mucociliary Clearance
  evidence:
  - reference: ORPHA:244
    supports: SUPPORT
    snippet: "A rare, genetically heterogeneous, primarily respiratory disorder characterized by chronic upper and lower respiratory tract disease."
    explanation: Orphanet definition confirms PCD is characterized by ciliary dysfunction leading to chronic respiratory disease.
  - reference: PMID:19818430
    reference_title: "[Primary ciliary dyskinesia. Ciliopathies]."
    supports: SUPPORT
    snippet: Primary ciliary dyskinesia is a genetically inherited syndrome characterized by cilia immotility or dysmotility. Deficiency in mucociliary clearance produces chronic respiratory infections since birth.
    explanation: The reference confirms that defects in the structure and function of motile cilia impair mucociliary clearance, supporting the statement.
  - reference: PMID:20525503
    reference_title: "Cilia dysfunction."
    supports: SUPPORT
    snippet: Ciliary dysfunction may be primary, the result of genetic mutations resulting in abnormal cilia structure, or secondary, the result of environmental, infectious or inflammatory stimuli that disrupt normal motility or coordination.
    explanation: This reference supports the statement by indicating that primary ciliary dyskinesia results from genetic mutations affecting cilia structure and function, leading to impaired mucociliary clearance.
  - reference: PMID:17059358
    reference_title: "Genetic defects in ciliary structure and function."
    supports: SUPPORT
    snippet: The most prominent genetic abnormality involving motile cilia (and the respiratory tract) is primary ciliary dyskinesia (PCD). PCD is a rare, usually autosomal recessive, genetically heterogeneous disorder characterized by sino-pulmonary disease, laterality defects, and male infertility.
    explanation: The reference supports the statement by describing PCD as a disorder involving motile cilia defects, which leads to respiratory issues due to impaired mucociliary clearance.
  - reference: PMID:15750039
    reference_title: "Mislocalization of DNAH5 and DNAH9 in respiratory cells from patients with primary ciliary dyskinesia."
    supports: SUPPORT
    snippet: Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder characterized by recurrent infections of the airways and situs inversus in half of the affected offspring. The most frequent genetic defects comprise recessive mutations of DNAH5 and DNAI1, which encode outer dynein arm (ODA) components.
    explanation: This reference supports the statement by listing DNAH5 and DNAI1 as genes involved in PCD, which is characterized by defects in motile cilia leading to impaired mucociliary clearance.
  - reference: PMID:32185794
    reference_title: "A nonsense variant in NME5 causes human primary ciliary dyskinesia with radial spoke defects."
    supports: SUPPORT
    snippet: Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder characterized by defects in the function or structure of motitle cilia
    explanation: The reference supports the statement by confirming that PCD involves defects in the structure and function of motile cilia, which impair mucociliary clearance.
- name: Impaired Mucociliary Clearance
  description: Failure to effectively remove mucus and pathogens from respiratory passages.
  biological_processes:
  - preferred_term: mucociliary clearance
    term:
      id: GO:0120197
      label: mucociliary clearance
  locations:
  - preferred_term: respiratory system
    term:
      id: UBERON:0001004
      label: respiratory system
  - preferred_term: paranasal sinus
    term:
      id: UBERON:0001825
      label: paranasal sinus
  downstream:
  - target: Chronic Respiratory Infections
  - target: Sinusitis
  - target: Otitis Media
  evidence:
  - reference: PMID:11376511
    reference_title: "Pathophysiology and treatment of airway mucociliary clearance. A moving tale."
    supports: SUPPORT
    snippet: Failure to keep the airways sterile by MCC results in a host inflammatory response to the persistent microorganisms which, if it becomes chronic, causes damage to the airway wall and upregulation of mucus production manifest clinically as bronchiectasis, sinusitis and otitis.
    explanation: The literature supports that primary ciliary dyskinesia (PCD) leads to impaired mucociliary clearance, which results in chronic respiratory infections, sinusitis, and otitis media.
  - reference: PMID:17142159
    reference_title: "Primary ciliary dyskinesia and newborn respiratory distress."
    supports: SUPPORT
    snippet: Primary ciliary dyskinesia is an autosomal recessive genetic disease that results in impaired mucociliary clearance causing progressive involvement of the upper and lower respiratory tract, characterized by airway obstruction and recurrent infections of the lungs, middle ear and paranasal sinuses.
    explanation: The literature supports that primary ciliary dyskinesia leads to impaired mucociliary clearance and downstream chronic respiratory infections, sinusitis, and otitis media.
  - reference: PMID:15917207
    reference_title: "Cilia and disease."
    supports: SUPPORT
    snippet: Disruption of 9+2 cilia, which move mucus across respiratory epithelia, leads to rhinitis, sinusitis and bronchiectasis.
    explanation: The literature supports that disruption of motile cilia, as seen in primary ciliary dyskinesia, leads to impaired mucociliary clearance and resultant respiratory conditions such as sinusitis and bronchiectasis.
  - reference: PMID:29490941
    reference_title: "Olfactory dysfunction is worse in primary ciliary dyskinesia compared with other causes of chronic sinusitis in children."
    supports: SUPPORT
    snippet: 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.
    explanation: The literature supports that primary ciliary dyskinesia leads to impaired mucociliary clearance and associated conditions such as sinusitis.
- name: Situs Inversus
  description: Abnormal placement of internal organs due to ciliary dysfunction during embryonic development.
  frequency: 50%
  biological_processes:
  - preferred_term: determination of left/right symmetry
    term:
      id: GO:0007368
      label: determination of left/right symmetry
  - preferred_term: nodal cilium assembly
    term:
      id: GO:0044458
      label: motile cilium assembly
  locations:
  - preferred_term: embryo
    term:
      id: UBERON:0000922
      label: embryo
  evidence:
  - reference: ORPHA:244
    supports: SUPPORT
    snippet: "Approximately half of the patients have an organ laterality defect (situs inversus totalis or situs ambiguus/heterotaxy)."
    explanation: Orphanet definition confirms that approximately half of PCD patients have laterality defects.
  - reference: PMID:16036877
    reference_title: "Primary ciliary dyskinesia: a review."
    supports: PARTIAL
    snippet: The normal left-right asymmetry of the body is thought to be due to the beating of the cilia in the embryonic (Hensen's) node. Total immotility of the cilia should therefore result in random asymmetry of the body that is situs inversus in 50% of the cases. It has also been claimed that 50% of cases with PCD have situs inversus.
    explanation: The statement is partially supported. The literature confirms that primary ciliary dyskinesia (PCD) can lead to situs inversus due to ciliary dysfunction during embryonic development, and it is claimed that 50% of PCD cases have situs inversus. However, the phrase 'abnormal placement of internal organs' is more general and could include other forms of laterality defects, not just situs inversus.
  - reference: PMID:36342963
    reference_title: "Laterality Defects in Primary Ciliary Dyskinesia: Relationship to Ultrastructural Defect or Genotype."
    supports: PARTIAL
    snippet: 'Results: Of 559 participants, 286 (51.2%), 215 (38.5%), and 58 (10.4%) were identified as having situs solitus, situs inversustotalis, and situs ambiguus, respectively; heterotaxy, defined as situs ambiguus with complex cardiovascular defects, was present in 14 (2.5%)'
    explanation: The statement is partially supported. The data shows that 38.5% of PCD cases have situs inversus totalis, which is close to but not exactly 50%. Additionally, there are other laterality defects like situs ambiguus, which are not covered by the statement.
phenotypes:
- category: Respiratory
  name: Chronic Cough
  frequency: VERY_FREQUENT
  diagnostic: true
  evidence:
  - reference: PMID:27258773
    reference_title: "Toward an Earlier Diagnosis of Primary Ciliary Dyskinesia. Which Patients Should Undergo Detailed Diagnostic Testing?"
    supports: SUPPORT
    snippet: Primary ciliary dyskinesia (PCD) is a rare, heterogeneous, recessive, genetic disorder of motile cilia, leading to chronic upper and lower respiratory symptoms.
    explanation: The statement is supported because PCD leads to chronic respiratory symptoms, including chronic cough.
  - reference: PMID:17142159
    reference_title: "Primary ciliary dyskinesia and newborn respiratory distress."
    supports: SUPPORT
    snippet: Primary ciliary dyskinesia is an autosomal recessive genetic disease that results in impaired mucociliary clearance causing progressive involvement of the upper and lower respiratory tract, characterized by airway obstruction and recurrent infections of the lungs, middle ear and paranasal sinuses.
    explanation: The statement is supported because PCD causes progressive involvement of the respiratory tract, which includes chronic cough.
  phenotype_term:
    preferred_term: Chronic Cough
    term:
      id: HP:0034315
      label: Chronic cough
- category: Respiratory
  name: Recurrent Respiratory Infections
  frequency: VERY_FREQUENT
  evidence:
  - reference: PMID:39069333
    reference_title: "Respiratory Aspects of Primary Ciliary Dyskinesia."
    supports: SUPPORT
    snippet: This review article explores the respiratory aspects of primary ciliary dyskinesia (PCD), a rare, heterogenous, genetic disorder characterized by impaired motile ciliary function. It discusses the clinical diagnosis and management strategies for PCD-related respiratory disease, including chronic sinusitis, otitis media with effusion, recurrent pneumonia, and bronchiectasis.
    explanation: The article discusses recurrent respiratory diseases as a significant aspect of PCD, supporting the statement that recurrent respiratory infections are very frequent in PCD.
  - reference: PMID:36214320
    reference_title: "In vitro measurement of ciliary beat frequency in 92 children with recurrent respiratory tract problems."
    supports: SUPPORT
    snippet: 'Ninety-two children with chronic respiratory symptoms were divided into 4 groups: 18 children with refractory asthma, 10 with bronchiectasis without dextrocardia, 18 with dextrocardia and 46 with recurrent respiratory tract infections.'
    explanation: The study highlights recurrent respiratory tract infections in children with chronic respiratory symptoms, supporting the statement that recurrent respiratory infections are very frequent in PCD.
  - reference: PMID:31430425
    reference_title: "Prevalence of chronic rhinosinusitis in bronchiectasis patients suspected of ciliary dyskinesia."
    supports: SUPPORT
    snippet: The objective of this study was to evaluate the prevalence of chronic rhinosinusitis (CRS) and its characteristics in bronchiectasis patients suspected of harboring ciliary dyskinesia.
    explanation: The study mentions chronic rhinosinusitis and bronchiectasis in patients suspected of ciliary dyskinesia, indicating frequent respiratory issues.
  - reference: PMID:25370419
    reference_title: "Simultaneous sinus and lung infections in patients with primary ciliary dyskinesia."
    supports: SUPPORT
    snippet: The sinuses should be considered as a bacterial reservoir and a target for surgery and antibiotic treatment in patients with primary ciliary dyskinesia (PCD).
    explanation: The study discusses sinus infections as a common issue in PCD, supporting the statement about frequent respiratory infections.
  phenotype_term:
    preferred_term: Recurrent Respiratory Infections
    term:
      id: HP:0002205
      label: Recurrent respiratory infections
- category: Respiratory
  name: Bronchiectasis
  frequency: FREQUENT
  evidence:
  - reference: ORPHA:244
    supports: PARTIAL
    snippet: "HP:0002110 | Bronchiectasis | Occasional (29-5%)"
    explanation: Orphanet classifies bronchiectasis as occasional (29-5%), likely reflecting cross-sectional point prevalence rather than cumulative incidence; multiple PMIDs describe it as a defining long-term complication of PCD.
  - reference: PMID:10894096
    reference_title: "Ciliary assessment in bronchiectasis."
    supports: SUPPORT
    snippet: Patients with primary ciliary dyskinesia could potentially develop recurrent sinotrachrobronchitis, bronchiectasis, serous otitis media, hydrocephalus, and male infertility.
    explanation: The article mentions bronchiectasis as one of the potential conditions that patients with PCD could develop.
  - reference: PMID:36344229
    reference_title: "[Sinusitis, otitis media and diffuse bronchiectasis in both lungs]."
    supports: SUPPORT
    snippet: Typical manifestations include bronchiectasis, secretory otitis media, sinusitis, situs inversus, and infertility.
    explanation: The article lists bronchiectasis as a typical manifestation of primary ciliary dyskinesia.
  - reference: PMID:25673230
    reference_title: "Lung structure-function correlation in patients with primary ciliary dyskinesia."
    supports: SUPPORT
    snippet: Primary ciliary dyskinesia (PCD) is a rare disease, characterised by chronic airway infection.
    explanation: The article discusses the relationship between functional and structural abnormalities in PCD, including bronchiectasis.
  - reference: PMID:21680564
    reference_title: "Cystic fibrosis, primary ciliary dyskinesia and non-cystic fibrosis bronchiectasis: update 2008-11."
    supports: SUPPORT
    snippet: A review is presented of key clinical papers published in Thorax and elsewhere between 2008 and April 2011 which have advanced our understanding of cystic fibrosis (CF), primary ciliary dyskinesia and non-CF bronchiectasis.
    explanation: The article discusses primary ciliary dyskinesia and non-CF bronchiectasis, implying a connection between PCD and bronchiectasis.
  - reference: PMID:31430425
    reference_title: "Prevalence of chronic rhinosinusitis in bronchiectasis patients suspected of ciliary dyskinesia."
    supports: SUPPORT
    snippet: The objective of this study was to evaluate the prevalence of chronic rhinosinusitis (CRS) and its characteristics in bronchiectasis patients suspected of harboring ciliary dyskinesia.
    explanation: The study evaluates bronchiectasis in patients suspected of having ciliary dyskinesia, indicating a frequent association.
  - reference: PMID:37278553
    reference_title: "Primary ciliary dyskinesia as a common cause of bronchiectasis in the Canadian Inuit population."
    supports: SUPPORT
    snippet: Primary ciliary dyskinesia as a common cause of bronchiectasis in the Canadian Inuit population.
    explanation: The article explicitly states that PCD is a common cause of bronchiectasis in a specific population.
  - reference: PMID:33895745
    reference_title: "The Primary Ciliary Dyskinesia Computed Tomography Score in Adults with Bronchiectasis: A Derivation und Validation Study."
    supports: SUPPORT
    snippet: Primary ciliary dyskinesia (PCD) is a rare genetic disorder which requires a complex diagnostic workup. Thus, an easy and widely available screening method would be helpful to identify patients who need a further diagnostic workup for PCD.
    explanation: The article discusses the need for diagnostic workup for PCD in patients with bronchiectasis, indicating a frequent association.
  - reference: PMID:23181248
    reference_title: "Congenital problems of mucociliary clearance: primary ciliary dyskinesia."
    supports: SUPPORT
    snippet: Mucociliary clearance is a primary defence mechanism of the airway that can be altered in congenital diseases such as primary ciliary dyskinesia and cystic fibrosis, as well as acquired conditions.
    explanation: The article focuses on primary ciliary dyskinesia and its impact on mucociliary clearance, which is related to bronchiectasis.
  - reference: PMID:37852905
    reference_title: "Bardet-Biedl Syndrome: An Uncommon Cause of Bronchiectasis."
    supports: NO_EVIDENCE
    snippet: 'Bardet-Biedl Syndrome: An Uncommon Cause of Bronchiectasis.'
    explanation: The article discusses Bardet-Biedl Syndrome as a cause of bronchiectasis, not primary ciliary dyskinesia.
  phenotype_term:
    preferred_term: Bronchiectasis
    term:
      id: HP:0002110
      label: Bronchiectasis
- category: Otologic
  name: Chronic Otitis Media
  frequency: FREQUENT
  evidence:
  - reference: ORPHA:244
    supports: SUPPORT
    snippet: "HP:0000389 | Chronic otitis media | Frequent (79-30%)"
    explanation: Orphanet phenotype data classifies chronic otitis media as frequent (79-30%) in primary ciliary dyskinesia.
  - reference: PMID:29135867
    reference_title: "Analysis of Otologic Features of Patients With Primary Ciliary Dyskinesia."
    supports: SUPPORT
    snippet: All 15 patients showed ciliary ultrastructural abnormalities on electron microscopy and/or biallelic mutations in genes associated with ciliary function or structure. All 30 eardrums examined showed certain abnormalities. Fourteen patients had otitis media with effusion or its sequelae. The remaining patient had chronic otitis media.
    explanation: The study found that patients with primary ciliary dyskinesia (PCD) frequently exhibited otologic issues, including chronic otitis media.
  - reference: PMID:19796826
    reference_title: "Management of otitis media with effusion in children with primary ciliary dyskinesia: a literature review."
    supports: SUPPORT
    snippet: Primary ciliary dyskinesia is an autosomal recessively inherited group of disorders of ciliary ultrastructure. Otolaryngologists are frequently involved in the management of some of the most common symptoms of primary ciliary dyskinesia including chronic rhinitis, sinusitis and otitis media with effusion.
    explanation: This reference supports that chronic otitis media and other otologic issues are common in patients with primary ciliary dyskinesia.
  phenotype_term:
    preferred_term: Chronic Otitis Media
    term:
      id: HP:0000389
      label: Chronic otitis media
- category: Otologic
  name: Hearing Loss
  frequency: OCCASIONAL
  evidence:
  - reference: ORPHA:244
    supports: SUPPORT
    snippet: "HP:0000365 | Hearing impairment | Occasional (29-5%)"
    explanation: Orphanet phenotype data classifies hearing impairment as occasional (29-5%) in primary ciliary dyskinesia.
  - reference: PMID:29287859
    reference_title: "Hearing loss in children with primary ciliary dyskinesia."
    supports: REFUTE
    snippet: Slight to mild CHL and all types of otitis media are prevalent among patients with PCD, and some of these children have sensorineural hearing loss (SNHL).
    explanation: The study indicates that hearing loss is a prevalent condition among patients with primary ciliary dyskinesia (PCD), not occasional.
  - reference: PMID:9222635
    reference_title: "Otological manifestations of primary ciliary dyskinesia."
    supports: REFUTE
    snippet: All children (11 patients) had bilateral otitis media with effusion. Of the five adults, three had tympanosclerosis; one had bilateral cholesteatoma; and one patient had bilateral keratosis obturans in combination with tympanosclerosis.
    explanation: The study describes otological manifestations including hearing loss as a prominent feature in patients with PCD, suggesting it is not occasional but rather common.
  - reference: PMID:33844744
    reference_title: "Observed Frequency and Characteristics of Hearing Loss in Osteogenesis Imperfecta."
    supports: NO_EVIDENCE
    snippet: In this group of patients with OI, 30% had hearing loss and among those ears with normal hearing, 13% did not have an acoustic stapedial reflex.
    explanation: This study discusses hearing loss in osteogenesis imperfecta (OI), not primary ciliary dyskinesia (PCD).
  phenotype_term:
    preferred_term: Hearing Loss
    term:
      id: HP:0000365
      label: Hearing impairment
- category: Otorhinolaryngologic
  name: Nasal Polyposis
  phenotype_term:
    preferred_term: Nasal Polyposis
    term:
      id: HP:0100582
      label: Nasal polyposis
  frequency: FREQUENT
  evidence:
  - reference: ORPHA:244
    supports: SUPPORT
    snippet: "HP:0100582 | Nasal polyposis | Frequent (79-30%)"
    explanation: Orphanet phenotype data classifies nasal polyposis as frequent (79-30%) in primary ciliary dyskinesia.
  - reference: PMID:37997295
    reference_title: "Histologic characterization of primary ciliary dyskinesia chronic rhinosinusitis."
    supports: NO_EVIDENCE
    snippet: Despite endoscopic differences, PCD-CRS and cystic fibrosis-related chronic rhinosinusitis (CF-CRS) had similar structured histopathology reports. Compared to healthy patients and those with idiopathic chronic rhinosinusitis without nasal polyps, patients with PCD-CRS had an increased neutrophil count.
    explanation: The abstract discusses histopathology and neutrophil count in PCD-CRS, but does not provide evidence on the frequency of nasal polyps in PCD.
  - reference: PMID:39069333
    reference_title: "Respiratory Aspects of Primary Ciliary Dyskinesia."
    supports: NO_EVIDENCE
    snippet: This review article explores the respiratory aspects of primary ciliary dyskinesia (PCD), a rare, heterogenous, genetic disorder characterized by impaired motile ciliary function. It discusses the clinical diagnosis and management strategies for PCD-related respiratory disease, including chronic sinusitis, otitis media with effusion, recurrent pneumonia, and bronchiectasis.
    explanation: The review focuses on respiratory aspects of PCD and does not mention nasal polyps as a frequent gastrointestinal manifestation.
- category: Cardiac
  name: Situs Inversus Totalis
  frequency: FREQUENT
  evidence:
  - reference: ORPHA:244
    supports: PARTIAL
    snippet: "HP:0001696 | Situs inversus totalis | Occasional (29-5%)"
    explanation: Orphanet classifies situs inversus totalis as occasional (29-5%), but literature data shows ~38-50% prevalence, supporting FREQUENT.
  - reference: PMID:16036877
    reference_title: "Primary ciliary dyskinesia: a review."
    supports: PARTIAL
    snippet: Total immotility of the cilia should therefore result in random asymmetry of the body that is situs inversus in 50% of the cases. It has also been claimed that 50% of cases with PCD have situs inversus.
    explanation: The literature indicates that situs inversus, including situs inversus totalis, occurs in approximately 50% of primary ciliary dyskinesia (PCD) cases. This suggests that it is not merely 'occasional' but rather relatively common in PCD patients.
  - reference: PMID:36342963
    reference_title: "Laterality Defects in Primary Ciliary Dyskinesia: Relationship to Ultrastructural Defect or Genotype."
    supports: PARTIAL
    snippet: 'Results: Of 559 participants, 286 (51.2%), 215 (38.5%), and 58 (10.4%) were identified as having situs solitus, situs inversustotalis, and situs ambiguus, respectively; heterotaxy, defined as situs ambiguus with complex cardiovascular defects, was present in 14 (2.5%)'
    explanation: The data indicates that situs inversus totalis occurs in 38.5% of PCD cases, which is more frequent than 'occasional.'
  - reference: PMID:38072392
    reference_title: "Situs Ambiguus Is Associated With Adverse Clinical Outcomes in Children With Primary Ciliary Dyskinesia."
    supports: PARTIAL
    snippet: The remaining 355 participants did not have SA, including 152 with SIT and 203 with SS.
    explanation: Situs inversus totalis (SIT) is present in a significant portion of PCD cases, indicating it is more common than 'occasional.'
  phenotype_term:
    preferred_term: Situs Inversus Totalis
    term:
      id: HP:0001696
      label: Situs inversus totalis
- category: Respiratory
  name: Chronic Respiratory Infections
  frequency: FREQUENT
  phenotype_term:
    preferred_term: Chronic Respiratory Infections
    term:
      id: HP:0002205
      label: Recurrent respiratory infections
- category: Respiratory
  name: Sinusitis
  frequency: FREQUENT
  phenotype_term:
    preferred_term: Sinusitis
    term:
      id: HP:0000246
      label: Sinusitis
- category: Otologic
  name: Otitis Media
  frequency: FREQUENT
  phenotype_term:
    preferred_term: Otitis Media
    term:
      id: HP:0000388
      label: Otitis media
- category: Respiratory
  name: Neonatal Respiratory Distress
  frequency: FREQUENT
  notes: Common presenting feature in newborns with PCD
  evidence:
  - reference: ORPHA:244
    supports: SUPPORT
    snippet: "HP:0002643 | Neonatal respiratory distress | Frequent (79-30%)"
    explanation: Orphanet phenotype data classifies neonatal respiratory distress as frequent (79-30%) in primary ciliary dyskinesia.
  - reference: PMID:19720631
    supports: SUPPORT
    snippet: "73% had a history of neonatal respiratory distress."
    explanation: In a consanguineous British Asian PCD cohort, 73% of patients had neonatal respiratory distress.
  phenotype_term:
    preferred_term: Neonatal respiratory distress
    term:
      id: HP:0002643
      label: Neonatal respiratory distress
- category: Reproductive
  name: Male Infertility
  frequency: FREQUENT
  notes: Due to sperm flagellar defects affecting motility
  evidence:
  - reference: ORPHA:244
    supports: SUPPORT
    snippet: "HP:0003251 | Male infertility | Frequent (79-30%)"
    explanation: Orphanet phenotype data classifies male infertility as frequent (79-30%) in primary ciliary dyskinesia.
  phenotype_term:
    preferred_term: Male infertility
    term:
      id: HP:0003251
      label: Male infertility
- category: Respiratory
  name: Chronic Rhinosinusitis
  frequency: FREQUENT
  notes: Chronic inflammation of nasal passages and sinuses
  evidence:
  - reference: ORPHA:244
    supports: SUPPORT
    snippet: "HP:0011109 | Chronic sinusitis | Frequent (79-30%)"
    explanation: Orphanet phenotype data classifies chronic sinusitis as frequent (79-30%) in primary ciliary dyskinesia.
  phenotype_term:
    preferred_term: Chronic rhinosinusitis
    term:
      id: HP:0011109
      label: Chronic sinusitis
- category: Respiratory
  name: Productive Cough
  frequency: FREQUENT
  evidence:
  - reference: ORPHA:244
    supports: SUPPORT
    snippet: "HP:0031245 | Productive cough | Frequent (79-30%)"
    explanation: Orphanet phenotype data classifies productive cough as frequent (79-30%) in primary ciliary dyskinesia.
  phenotype_term:
    preferred_term: Productive cough
    term:
      id: HP:0031245
      label: Productive cough
- category: Respiratory
  name: Recurrent Sinopulmonary Infections
  frequency: FREQUENT
  evidence:
  - reference: ORPHA:244
    supports: SUPPORT
    snippet: "HP:0005425 | Recurrent sinopulmonary infections | Frequent (79-30%)"
    explanation: Orphanet phenotype data classifies recurrent sinopulmonary infections as frequent (79-30%) in primary ciliary dyskinesia.
  phenotype_term:
    preferred_term: Recurrent sinopulmonary infections
    term:
      id: HP:0005425
      label: Recurrent sinopulmonary infections
- category: Respiratory
  name: Nasal Congestion
  frequency: FREQUENT
  evidence:
  - reference: ORPHA:244
    supports: SUPPORT
    snippet: "HP:0001742 | Nasal congestion | Frequent (79-30%)"
    explanation: Orphanet phenotype data classifies nasal congestion as frequent (79-30%) in primary ciliary dyskinesia.
  phenotype_term:
    preferred_term: Nasal congestion
    term:
      id: HP:0001742
      label: Nasal congestion
- category: Respiratory
  name: Chronic Rhinitis
  frequency: FREQUENT
  evidence:
  - reference: ORPHA:244
    supports: SUPPORT
    snippet: "HP:0002257 | Chronic rhinitis | Frequent (79-30%)"
    explanation: Orphanet phenotype data classifies chronic rhinitis as frequent (79-30%) in primary ciliary dyskinesia.
  phenotype_term:
    preferred_term: Chronic rhinitis
    term:
      id: HP:0002257
      label: Chronic rhinitis
- category: Respiratory
  name: Abnormal Sputum
  frequency: FREQUENT
  evidence:
  - reference: ORPHA:244
    supports: SUPPORT
    snippet: "HP:0032016 | Abnormal sputum | Frequent (79-30%)"
    explanation: Orphanet phenotype data classifies abnormal sputum as frequent (79-30%) in primary ciliary dyskinesia.
  phenotype_term:
    preferred_term: Abnormal sputum
    term:
      id: HP:0032016
      label: Abnormal sputum
- category: Reproductive
  name: Abnormal Sperm Motility
  frequency: FREQUENT
  evidence:
  - reference: ORPHA:244
    supports: SUPPORT
    snippet: "HP:0012206 | Abnormal sperm motility | Frequent (79-30%)"
    explanation: Orphanet phenotype data classifies abnormal sperm motility as frequent (79-30%) in primary ciliary dyskinesia.
  phenotype_term:
    preferred_term: Abnormal sperm motility
    term:
      id: HP:0012206
      label: Abnormal sperm motility
- category: Otologic
  name: Recurrent Otitis Media
  frequency: FREQUENT
  evidence:
  - reference: ORPHA:244
    supports: SUPPORT
    snippet: "HP:0000403 | Recurrent otitis media | Frequent (79-30%)"
    explanation: Orphanet phenotype data classifies recurrent otitis media as frequent (79-30%) in primary ciliary dyskinesia.
  phenotype_term:
    preferred_term: Recurrent otitis media
    term:
      id: HP:0000403
      label: Recurrent otitis media
- category: Respiratory
  name: Wheezing
  frequency: OCCASIONAL
  evidence:
  - reference: ORPHA:244
    supports: SUPPORT
    snippet: "HP:0030828 | Wheezing | Occasional (29-5%)"
    explanation: Orphanet phenotype data classifies wheezing as occasional (29-5%) in primary ciliary dyskinesia.
  phenotype_term:
    preferred_term: Wheezing
    term:
      id: HP:0030828
      label: Wheezing
- category: Reproductive
  name: Female Infertility
  frequency: OCCASIONAL
  notes: Due to impaired ciliary function in fallopian tubes
  evidence:
  - reference: ORPHA:244
    supports: SUPPORT
    snippet: "HP:0008222 | Female infertility | Occasional (29-5%)"
    explanation: Orphanet phenotype data classifies female infertility as occasional (29-5%) in primary ciliary dyskinesia.
  phenotype_term:
    preferred_term: Female infertility
    term:
      id: HP:0008222
      label: Female infertility
- category: Respiratory
  name: Atelectasis
  frequency: OCCASIONAL
  evidence:
  - reference: ORPHA:244
    supports: SUPPORT
    snippet: "HP:0100750 | Atelectasis | Occasional (29-5%)"
    explanation: Orphanet phenotype data classifies atelectasis as occasional (29-5%) in primary ciliary dyskinesia.
  phenotype_term:
    preferred_term: Atelectasis
    term:
      id: HP:0100750
      label: Atelectasis
- category: Otologic
  name: Conductive Hearing Impairment
  frequency: OCCASIONAL
  evidence:
  - reference: ORPHA:244
    supports: SUPPORT
    snippet: "HP:0000405 | Conductive hearing impairment | Occasional (29-5%)"
    explanation: Orphanet phenotype data classifies conductive hearing impairment as occasional (29-5%) in primary ciliary dyskinesia.
  phenotype_term:
    preferred_term: Conductive hearing impairment
    term:
      id: HP:0000405
      label: Conductive hearing impairment
- category: Respiratory
  name: Airway Obstruction
  frequency: OCCASIONAL
  evidence:
  - reference: ORPHA:244
    supports: SUPPORT
    snippet: "HP:0006536 | Airway obstruction | Occasional (29-5%)"
    explanation: Orphanet phenotype data classifies airway obstruction as occasional (29-5%) in primary ciliary dyskinesia.
  phenotype_term:
    preferred_term: Airway obstruction
    term:
      id: HP:0006536
      label: Airway obstruction
- category: Respiratory
  name: Digital Clubbing
  frequency: OCCASIONAL
  evidence:
  - reference: ORPHA:244
    supports: SUPPORT
    snippet: "HP:0001217 | Clubbing | Occasional (29-5%)"
    explanation: Orphanet phenotype data classifies digital clubbing as occasional (29-5%) in primary ciliary dyskinesia.
  phenotype_term:
    preferred_term: Clubbing
    term:
      id: HP:0001217
      label: Clubbing
- category: Cardiac
  name: Abnormal Heart Morphology
  frequency: OCCASIONAL
  notes: Congenital heart defects associated with laterality abnormalities
  evidence:
  - reference: ORPHA:244
    supports: SUPPORT
    snippet: "HP:0001627 | Abnormal heart morphology | Occasional (29-5%)"
    explanation: Orphanet phenotype data classifies abnormal heart morphology as occasional (29-5%) in primary ciliary dyskinesia.
  phenotype_term:
    preferred_term: Abnormal heart morphology
    term:
      id: HP:0001627
      label: Abnormal heart morphology
- category: Neurologic
  name: Hydrocephalus
  frequency: VERY_RARE
  notes: Related to ependymal ciliary dysfunction
  evidence:
  - reference: ORPHA:244
    supports: SUPPORT
    snippet: "HP:0000238 | Hydrocephalus | Very rare (<4-1%)"
    explanation: Orphanet phenotype data classifies hydrocephalus as very rare (<4-1%) in primary ciliary dyskinesia.
  phenotype_term:
    preferred_term: Hydrocephalus
    term:
      id: HP:0000238
      label: Hydrocephalus
- category: Respiratory
  name: Respiratory Failure
  frequency: VERY_RARE
  evidence:
  - reference: ORPHA:244
    supports: SUPPORT
    snippet: "HP:0002878 | Respiratory failure | Very rare (<4-1%)"
    explanation: Orphanet phenotype data classifies respiratory failure as very rare (<4-1%) in primary ciliary dyskinesia.
  phenotype_term:
    preferred_term: Respiratory failure
    term:
      id: HP:0002878
      label: Respiratory failure
- category: Gastrointestinal
  name: Intestinal Malrotation
  frequency: VERY_RARE
  notes: Associated with situs abnormalities
  evidence:
  - reference: ORPHA:244
    supports: SUPPORT
    snippet: "HP:0002566 | Intestinal malrotation | Very rare (<4-1%)"
    explanation: Orphanet phenotype data classifies intestinal malrotation as very rare (<4-1%) in primary ciliary dyskinesia.
  phenotype_term:
    preferred_term: Intestinal malrotation
    term:
      id: HP:0002566
      label: Intestinal malrotation
biochemical:
- name: Nitric Oxide
  presence: Decreased
  context: Lower levels in nasal and exhaled breath
  evidence:
  - reference: PMID:12511725
    reference_title: "Comparison of exhaled and nasal nitric oxide and exhaled carbon monoxide levels in bronchiectatic patients with and without primary ciliary dyskinesia."
    supports: SUPPORT
    snippet: Low values in both eNO and nNO readings (<2.4 ppb and <187 ppb, respectively) identified PCD patients from other bronchiectatic patients with a specificity of 98% and a positive predictive value of 92%.
    explanation: This study shows that both exhaled nitric oxide (eNO) and nasal nitric oxide (nNO) levels are significantly lower in patients with primary ciliary dyskinesia (PCD) compared to other groups.
  - reference: PMID:22408195
    reference_title: "Nitric oxide in primary ciliary dyskinesia."
    supports: SUPPORT
    snippet: Despite chronic infections, nasal nitric oxide in such patients is markedly reduced and is used as a screening test for this condition.
    explanation: This abstract confirms that nasal nitric oxide levels are significantly reduced in PCD patients.
  - reference: PMID:31770003
    reference_title: "Nasal Nitric Oxide Measurement in Primary Ciliary Dyskinesia. A Technical Paper on Standardized Testing Protocols."
    supports: SUPPORT
    snippet: Nasal nitric oxide concentrations are extremely low in primary ciliary dyskinesia (PCD), and measurement of this nasal gas is recommended as a PCD diagnostic test in cooperative patients aged 5 years and older.
    explanation: This paper supports the statement by indicating that nasal nitric oxide levels are extremely low in PCD patients.
  - reference: PMID:35777446
    reference_title: "Longitudinal Nitric Oxide Levels and Infections by Ultrastructure and Genotype in Primary Ciliary Dyskinesia."
    supports: SUPPORT
    snippet: We hypothesized that differences in nasal nitric oxide (nNO) and fractional exhaled nitric oxide (Feno) relate to prognosis in primary ciliary dyskinesia (PCD).
    explanation: The study indicates that both nasal nitric oxide (nNO) and fractional exhaled nitric oxide (FeNO) levels are low in PCD patients and are used to monitor the condition.
  - reference: PMID:33860637
    reference_title: "Breath-holding and tidal breathing nasal NO to screen children for Primary Ciliary Dyskinesia."
    supports: SUPPORT
    snippet: Nasal nitric oxide (nNO) measurement is recommended to screen for Primary Ciliary Dyskinesia (PCD) in subjects with suggestive history and symptoms.
    explanation: This study supports the statement by recommending nasal nitric oxide measurement as a screening tool for PCD due to its low levels in such patients.
  - reference: PMID:29490941
    reference_title: "Olfactory dysfunction is worse in primary ciliary dyskinesia compared with other causes of chronic sinusitis in children."
    supports: SUPPORT
    snippet: 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).
    explanation: The study confirms that nasal nitric oxide levels are lower in PCD patients compared to non-PCD patients.
genetic:
- name: DNAI1
  association: Pathogenic Variants
  notes: Outer dynein arm intermediate chain required for ODA integrity and docking
  evidence:
  - reference: ORPHA:244
    supports: SUPPORT
    snippet: "DNAI1 | dynein axonemal intermediate chain 1 | hgnc:2954 | Disease-causing germline mutation(s) in"
    explanation: Orphanet gene-disease association data confirms DNAI1 as a disease-causing gene for primary ciliary dyskinesia.
  - reference: PMID:11893720
    reference_title: "Mutations in DNAI1 (IC78) cause primary ciliary dyskinesia."
    supports: SUPPORT
    snippet: Mutations in DNAI1 (IC78) cause primary ciliary dyskinesia.
    explanation: This study directly links mutations in DNAI1 to the cause of primary ciliary dyskinesia.
  - reference: PMID:35869935
    reference_title: "Pathogenic variants identified using whole-exome sequencing in Chinese patients with primary ciliary dyskinesia."
    supports: SUPPORT
    snippet: 13 rare variants were identified in patients with PCD, among which were three homozygous causative variants (including one splicing variant) in the PCD-associated genes CCDC40 and DNAI1.
    explanation: The study identifies causative variants in DNAI1 associated with primary ciliary dyskinesia.
  - reference: PMID:15750039
    reference_title: "Mislocalization of DNAH5 and DNAH9 in respiratory cells from patients with primary ciliary dyskinesia."
    supports: SUPPORT
    snippet: The most frequent genetic defects comprise recessive mutations of DNAH5 and DNAI1, which encode outer dynein arm (ODA) components.
    explanation: This study mentions DNAI1 mutations as frequent genetic defects causing primary ciliary dyskinesia.
  - reference: PMID:11231901
    reference_title: "Axonemal dynein intermediate-chain gene (DNAI1) mutations result in situs inversus and primary ciliary dyskinesia (Kartagener syndrome)."
    supports: SUPPORT
    snippet: We identified compound heterozygous DNAI1 gene defects in three independent patients and in two of their siblings who presented with PCD and situs solitus.
    explanation: The study links compound heterozygous DNAI1 gene defects with primary ciliary dyskinesia.
- name: DNAH5
  association: Pathogenic Variants
  notes: Major axonemal outer dynein arm heavy chain generating motile force
  evidence:
  - reference: ORPHA:244
    supports: SUPPORT
    snippet: "DNAH5 | dynein axonemal heavy chain 5 | hgnc:2950 | Disease-causing germline mutation(s) in"
    explanation: Orphanet gene-disease association data confirms DNAH5 as a disease-causing gene for primary ciliary dyskinesia.
  - reference: PMID:31118369
    reference_title: "A Japanese Case of Primary Ciliary Dyskinesia with DNAH5 Mutations."
    supports: SUPPORT
    snippet: A genetic examination detected compound heterozygous mutations of DNAH5 that encode ODA components.
    explanation: The study reports a case of primary ciliary dyskinesia (PCD) with DNAH5 mutations, confirming the association between PCD and pathogenic variants in DNAH5.
  - reference: PMID:36727596
    reference_title: "Pathogenic variants in CLXN encoding the outer dynein arm docking-associated calcium-binding protein calaxin cause primary ciliary dyskinesia."
    supports: SUPPORT
    snippet: Most PCD-causing variants result in abnormal outer dynein arms (ODAs), which provide the generative force for respiratory ciliary beating and proper mucociliary clearance.
    explanation: The study indicates that pathogenic variants causing PCD often result in abnormal ODAs, which are associated with DNAH5.
- name: DNAH11
  association: Pathogenic Variants
  notes: Outer dynein arm heavy chain often causing dyskinetic beating with near-normal ultrastructure; associated with milder lung function decline
  evidence:
  - reference: ORPHA:244
    supports: SUPPORT
    snippet: "DNAH11 | dynein axonemal heavy chain 11 | hgnc:2942 | Disease-causing germline mutation(s) in"
    explanation: Orphanet gene-disease association data confirms DNAH11 as a disease-causing gene for primary ciliary dyskinesia.
- name: CCDC39
  association: Pathogenic Variants
  notes: Nexin-dynein regulatory complex scaffold for inner dynein arms; associated with severe early lung disease and low lung function
  evidence:
  - reference: ORPHA:244
    supports: SUPPORT
    snippet: "CCDC39 | coiled-coil domain 39 molecular ruler complex subunit | hgnc:25244 | Disease-causing germline mutation(s) in"
    explanation: Orphanet gene-disease association data confirms CCDC39 as a disease-causing gene for primary ciliary dyskinesia.
- name: CCDC40
  association: Pathogenic Variants
  notes: Nexin-dynein regulatory complex scaffold partnering with CCDC39; associated with severe lung function decline and possible congenital heart disease
  evidence:
  - reference: ORPHA:244
    supports: SUPPORT
    snippet: "CCDC40 | coiled-coil domain 40 molecular ruler complex subunit | hgnc:26090 | Disease-causing germline mutation(s) in"
    explanation: Orphanet gene-disease association data confirms CCDC40 as a disease-causing gene for primary ciliary dyskinesia.
- name: RSPH1
  association: Pathogenic Variants
  notes: Radial spoke head component coordinating central pair-dynein regulation
  evidence:
  - reference: ORPHA:244
    supports: SUPPORT
    snippet: "RSPH1 | radial spoke head component 1 | hgnc:12371 | Disease-causing germline mutation(s) (loss of function) in"
    explanation: Orphanet gene-disease association data confirms RSPH1 as a disease-causing gene for primary ciliary dyskinesia.
- name: RSPH4A
  association: Pathogenic Variants
  notes: Radial spoke protein required for radial spoke integrity and coordinated beating
  evidence:
  - reference: ORPHA:244
    supports: SUPPORT
    snippet: "RSPH4A | radial spoke head component 4A | hgnc:21558 | Disease-causing germline mutation(s) in"
    explanation: Orphanet gene-disease association data confirms RSPH4A as a disease-causing gene for primary ciliary dyskinesia.
- name: RSPH9
  association: Pathogenic Variants
  notes: Radial spoke head subunit impacting central pair-radial spoke interactions
  evidence:
  - reference: ORPHA:244
    supports: SUPPORT
    snippet: "RSPH9 | radial spoke head component 9 | hgnc:21057 | Disease-causing germline mutation(s) in"
    explanation: Orphanet gene-disease association data confirms RSPH9 as a disease-causing gene for primary ciliary dyskinesia.
- name: CCNO
  association: Pathogenic Variants
  notes: Required for centriole amplification and multiciliogenesis; associated with oligocilia and very severe early disease with very low lung function
  evidence:
  - reference: ORPHA:244
    supports: SUPPORT
    snippet: "CCNO | cyclin O | hgnc:18576 | Disease-causing germline mutation(s) (loss of function) in"
    explanation: Orphanet gene-disease association data confirms CCNO as a disease-causing gene for primary ciliary dyskinesia.
- name: FOXJ1
  association: Pathogenic Variants
  notes: Master transcription factor regulating motile ciliogenesis; can present in autosomal dominant fashion
  evidence:
  - reference: ORPHA:244
    supports: SUPPORT
    snippet: "FOXJ1 | forkhead box J1 | hgnc:3816 | Disease-causing germline mutation(s) (loss of function) in"
    explanation: Orphanet gene-disease association data confirms FOXJ1 as a disease-causing gene for primary ciliary dyskinesia.
- name: MCIDAS
  association: Pathogenic Variants
  notes: Drives multiciliated cell differentiation and centriole biogenesis; associated with reduced cilia number
  evidence:
  - reference: ORPHA:244
    supports: SUPPORT
    snippet: "MCIDAS | multiciliate differentiation and DNA synthesis associated cell cycle protein | hgnc:40050 | Disease-causing germline mutation(s) (loss of function) in"
    explanation: Orphanet gene-disease association data confirms MCIDAS as a disease-causing gene for primary ciliary dyskinesia.
- name: ODAD1
  association: Pathogenic Variants
  notes: Outer dynein arm docking/assembly factor; associated with relatively milder lung function impact
  evidence:
  - reference: ORPHA:244
    supports: SUPPORT
    snippet: "ODAD1 | outer dynein arm docking complex subunit 1 | hgnc:26560 | Disease-causing germline mutation(s) (loss of function) in"
    explanation: Orphanet gene-disease association data confirms ODAD1 as a disease-causing gene for primary ciliary dyskinesia.
- name: CFAP221
  gene_term:
    preferred_term: CFAP221
    term:
      id: hgnc:33720
      label: CFAP221
  association: Pathogenic Variants
  evidence:
  - reference: CGGV:assertion_c7c841e5-2973-4f23-8603-970e9e2cbc92-2025-12-16T120000.000Z
    reference_title: "CFAP221 / primary ciliary dyskinesia (Definitive)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "CFAP221 | HGNC:33720 | primary ciliary dyskinesia | MONDO:0016575 | AR | Definitive"
    explanation: ClinGen classifies the CFAP221-primary ciliary dyskinesia gene-disease relationship as definitive with autosomal recessive inheritance.
- name: CFAP46
  gene_term:
    preferred_term: CFAP46
    term:
      id: hgnc:25247
      label: CFAP46
  association: Pathogenic Variants
  evidence:
  - reference: CGGV:assertion_eabe809a-1203-4d42-9052-21f39717754f-2025-10-17T160000.000Z
    reference_title: "CFAP46 / primary ciliary dyskinesia (Limited)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "CFAP46 | HGNC:25247 | primary ciliary dyskinesia | MONDO:0016575 | AR | Limited"
    explanation: ClinGen classifies the CFAP46-primary ciliary dyskinesia gene-disease relationship as limited with autosomal recessive inheritance.
- name: CFAP57
  gene_term:
    preferred_term: CFAP57
    term:
      id: hgnc:26485
      label: CFAP57
  association: Pathogenic Variants
  evidence:
  - reference: CGGV:assertion_50ed292f-0044-4c82-9419-a040cbcaf205-2022-06-23T160000.000Z
    reference_title: "CFAP57 / primary ciliary dyskinesia (Limited)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "CFAP57 | HGNC:26485 | primary ciliary dyskinesia | MONDO:0016575 | AR | Limited"
    explanation: ClinGen classifies the CFAP57-primary ciliary dyskinesia gene-disease relationship as limited with autosomal recessive inheritance.
- name: DAW1
  gene_term:
    preferred_term: DAW1
    term:
      id: hgnc:26383
      label: DAW1
  association: Pathogenic Variants
  evidence:
  - reference: CGGV:assertion_8610990f-63cf-466a-8cd7-fbf7ae58d0f2-2024-06-13T160000.000Z
    reference_title: "DAW1 / primary ciliary dyskinesia (Limited)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "DAW1 | HGNC:26383 | primary ciliary dyskinesia | MONDO:0016575 | AR | Limited"
    explanation: ClinGen classifies the DAW1-primary ciliary dyskinesia gene-disease relationship as limited with autosomal recessive inheritance.
- name: DNAH1
  gene_term:
    preferred_term: DNAH1
    term:
      id: hgnc:2940
      label: DNAH1
  association: Pathogenic Variants
  evidence:
  - reference: CGGV:assertion_a07c8b6e-a558-498b-975c-b12e96878a44-2025-10-16T160000.000Z
    reference_title: "DNAH1 / primary ciliary dyskinesia (Limited)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "DNAH1 | HGNC:2940 | primary ciliary dyskinesia | MONDO:0016575 | AR | Limited"
    explanation: ClinGen classifies the DNAH1-primary ciliary dyskinesia gene-disease relationship as limited with autosomal recessive inheritance.
- name: DNAH10
  gene_term:
    preferred_term: DNAH10
    term:
      id: hgnc:2941
      label: DNAH10
  association: Pathogenic Variants
  evidence:
  - reference: CGGV:assertion_698c6b23-a6fb-4b56-a38e-b29d5f8bbd86-2025-02-13T170000.000Z
    reference_title: "DNAH10 / primary ciliary dyskinesia (Limited)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "DNAH10 | HGNC:2941 | primary ciliary dyskinesia | MONDO:0016575 | AR | Limited"
    explanation: ClinGen classifies the DNAH10-primary ciliary dyskinesia gene-disease relationship as limited with autosomal recessive inheritance.
- name: DNAH7
  gene_term:
    preferred_term: DNAH7
    term:
      id: hgnc:18661
      label: DNAH7
  association: Pathogenic Variants
  evidence:
  - reference: CGGV:assertion_90a097d6-5127-4466-8c81-00e99dab2696-2025-02-13T170000.000Z
    reference_title: "DNAH7 / primary ciliary dyskinesia (Limited)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "DNAH7 | HGNC:18661 | primary ciliary dyskinesia | MONDO:0016575 | AR | Limited"
    explanation: ClinGen classifies the DNAH7-primary ciliary dyskinesia gene-disease relationship as limited with autosomal recessive inheritance.
- name: NME8
  gene_term:
    preferred_term: NME8
    term:
      id: hgnc:16473
      label: NME8
  association: Pathogenic Variants
  evidence:
  - reference: CGGV:assertion_57ca8383-55b6-4edd-9be2-67b1c5142ed1-2023-06-08T160000.000Z
    reference_title: "NME8 / primary ciliary dyskinesia (Limited)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "NME8 | HGNC:16473 | primary ciliary dyskinesia | MONDO:0016575 | AR | Limited"
    explanation: ClinGen classifies the NME8-primary ciliary dyskinesia gene-disease relationship as limited with autosomal recessive inheritance.
- name: SPEF2
  gene_term:
    preferred_term: SPEF2
    term:
      id: hgnc:26293
      label: SPEF2
  association: Pathogenic Variants
  evidence:
  - reference: CGGV:assertion_e137eed5-fcd8-4497-a6dc-6651062d1cf3-2025-01-09T170000.000Z
    reference_title: "SPEF2 / primary ciliary dyskinesia (Definitive)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "SPEF2 | HGNC:26293 | primary ciliary dyskinesia | MONDO:0016575 | AR | Definitive"
    explanation: ClinGen classifies the SPEF2-primary ciliary dyskinesia gene-disease relationship as definitive with autosomal recessive inheritance.
diagnosis:
- name: High-Speed Video Microscopy
  notes: Assess ciliary motion and structure
  evidence:
  - reference: PMID:38607006
    reference_title: "Advancing Primary Ciliary Dyskinesia Diagnosis through High-Speed Video Microscopy Analysis."
    supports: SUPPORT
    snippet: Our study implemented HSVA for the first time on the island as a tool to better diagnose and characterize the RSPH4A ... founder mutation in Puerto Rican patients.
    explanation: The study demonstrates the use of High-Speed Video Microscopy Analysis (HSVA) to assess ciliary motion and pattern in patients with Primary Ciliary Dyskinesia (PCD).
  - reference: PMID:29493257
    reference_title: "Seeing cilia: imaging modalities for ciliary motion and clinical connections."
    supports: SUPPORT
    snippet: Application of imaging modalities including transmission electron microscopy, high-speed video microscopy, and micron-optical coherence tomography could improve diagnostics and be applied for precision medicine.
    explanation: The review discusses the application of high-speed video microscopy among other imaging modalities to improve diagnostics in ciliopathic diseases, including PCD.
  - reference: PMID:26362507
    reference_title: "Diagnostic Methods in Primary Ciliary Dyskinesia."
    supports: SUPPORT
    snippet: We particularly focus on use of high-speed video analysis, transmission electron microscopy, nasal nitric oxide and genetic testing.
    explanation: The review highlights high-speed video analysis as one of the diagnostic methods for Primary Ciliary Dyskinesia.
- name: Transmission Electron Microscopy
  notes: Examines ciliary ultrastructure for diagnostic defects
  evidence:
  - reference: PMID:28915070
    reference_title: "Value of transmission electron microscopy for primary ciliary dyskinesia diagnosis in the era of molecular medicine: Genetic defects with normal and non-diagnostic ciliary ultrastructure."
    supports: PARTIAL
    snippet: Transmission electron microscopy (TEM) of respiratory cilia was previously considered the gold standard diagnostic test for PCD, but 30% of all PCD cases have either normal ciliary ultrastructure or subtle changes which are non-diagnostic.
    explanation: While TEM examines ciliary ultrastructure and can detect certain defects, it is not definitive for all cases of PCD, as some genetic mutations result in normal or non-diagnostic ultrastructure.
  - reference: PMID:10894096
    reference_title: "Ciliary assessment in bronchiectasis."
    supports: SUPPORT
    snippet: This brief article discusses application of the saccharine test, light microscopy assessment of ciliary beat, and transmission electron microscopy assessment of the ultrastructure of cilia.
    explanation: The reference supports that TEM is used to assess ciliary ultrastructure for diagnostic purposes.
  - reference: PMID:28891733
    reference_title: "Application of laboratory and digital techniques for visual enhancement during the ultrastructural assessment of cilia."
    supports: SUPPORT
    snippet: Routine diagnostic electron microscopy of primary ciliary dyskinesia (PCD) is based on the findings of ultrastructural defects of axonemal components.
    explanation: This reference confirms that TEM is used to examine ciliary ultrastructure for diagnostic defects in PCD.
- name: Nasal Nitric Oxide Test
  notes: Measures nasal nitric oxide levels, typically decreased in PCD patients
  evidence:
  - reference: PMID:31770003
    reference_title: "Nasal Nitric Oxide Measurement in Primary Ciliary Dyskinesia. A Technical Paper on Standardized Testing Protocols."
    supports: SUPPORT
    snippet: Nasal nitric oxide concentrations are extremely low in primary ciliary dyskinesia (PCD), and measurement of this nasal gas is recommended as a PCD diagnostic test in cooperative patients aged 5 years and older.
    explanation: The abstract clearly states that nasal nitric oxide concentrations are extremely low in PCD and that measuring this gas is recommended as a diagnostic test.
  - reference: PMID:29490941
    reference_title: "Olfactory dysfunction is worse in primary ciliary dyskinesia compared with other causes of chronic sinusitis in children."
    supports: SUPPORT
    snippet: Only in classical PCD did olfaction inversely correlate with sinusitis and nNO.
    explanation: The study mentions that nasal nitric oxide (nNO) levels are involved in the diagnosis of PCD.
  - reference: PMID:36285978
    reference_title: "Nasal Nitric Oxide Levels: Improving the Diagnosis of Primary Ciliary Dyskinesia in Puerto Rico."
    supports: SUPPORT
    snippet: The nNO level differentiated homozygous subjects with PCD due to the RSPH4A (c.921+3_921+6del (intronic)) founder mutation compared to healthy gender-age matched controls and subjects with VUS or negative genetic testing for PCD.
    explanation: The study demonstrates that nNO levels can differentiate PCD patients from healthy controls and those with other conditions.
  - reference: PMID:37385806
    reference_title: "[Diagnostic value of nasal nitric oxide for children with primary ciliary dyskinesia]."
    supports: SUPPORT
    snippet: nNO values were significantly lower in children with PCD than in PCD symptom-similar group and nNO normal controls.
    explanation: The study supports that nasal nitric oxide levels are significantly lower in children with PCD, making it a useful diagnostic tool.
  - reference: PMID:22408195
    reference_title: "Nitric oxide in primary ciliary dyskinesia."
    supports: SUPPORT
    snippet: Despite chronic infections, nasal nitric oxide in such patients is markedly reduced and is used as a screening test for this condition.
    explanation: The abstract confirms that nasal nitric oxide levels are markedly reduced in PCD patients and are used as a screening test.
environmental:
- name: Air Pollution
  effect: Exacerbates Symptoms
  evidence:
  - reference: PMID:34574829
    reference_title: "Effects of Air Pollutants on Airway Diseases."
    supports: SUPPORT
    snippet: Air pollution decreases quality of life and life expectancy. It exacerbates acute and chronic respiratory symptoms in patients with chronic airway diseases, and increases the morbidity and risk of hospitalization associated with respiratory diseases.
    explanation: The literature indicates that air pollution exacerbates respiratory symptoms in patients with chronic airway diseases, which can be inferred to include conditions like Primary Ciliary Dyskinesia (PCD).
  - reference: PMID:37147124
    reference_title: "Short-term air pollution exposure and exacerbation events in mild to moderate COPD: a case-crossover study within the CanCOLD cohort."
    supports: SUPPORT
    snippet: 'CONCLUSIONS: Short-term ambient NO2 and PM2.5 exposure were associated with increased odds of exacerbations in Canadians with mild to moderate COPD, further heightening the awareness of non-infectious triggers of COPD exacerbations'
    explanation: While this study focuses on COPD, it highlights the role of air pollution in exacerbating respiratory conditions, which can be extended to other chronic respiratory diseases like PCD.
  exposure_term:
    preferred_term: Air pollution exposure
    term:
      id: ECTO:8000036
      label: exposure to air pollution
treatments:
- name: Airway Clearance Techniques
  description: Methods to help clear mucus from the lungs, such as chest physical therapy.
  evidence:
  - reference: PMID:28408202
    reference_title: "Airway Clearance Techniques for Primary Ciliary Dyskinesia; is the Cystic Fibrosis literature portable?"
    supports: SUPPORT
    snippet: Airway clearance techniques (ACTs) are commonly recommended for patients with PCD to facilitate mucus clearance, despite a lack of evidence in this group.
    explanation: The reference acknowledges the use of airway clearance techniques in patients with Primary Ciliary Dyskinesia (PCD) to help clear mucus from the lungs.
  - reference: PMID:38861625
    reference_title: "Postural Drainage and Vibration."
    supports: SUPPORT
    snippet: Airway clearance techniques (ACTs) are critical in managing respiratory conditions characterized by mucus hypersecretion and impaired clearance, such as cystic fibrosis, chronic obstructive pulmonary disease (COPD), and various neuromuscular disorders.
    explanation: The reference discusses the importance of ACTs in managing conditions with mucus hypersecretion and impaired clearance, which aligns with the use of these techniques in PCD.
  - reference: PMID:11376511
    reference_title: "Pathophysiology and treatment of airway mucociliary clearance. A moving tale."
    supports: SUPPORT
    snippet: There are three principal disorders of MCC. Firstly, primary ciliary dyskinesia (PCD)...
    explanation: The reference mentions PCD and discusses airway hygiene and mucociliary clearance, supporting the relevance of airway clearance techniques in PCD.
  treatment_term:
    preferred_term: physical therapy
    term:
      id: MAXO:0000011
      label: physical therapy
- name: Antibiotic Therapy
  description: Long-term or prophylactic antibiotics to control respiratory infections.
  target_phenotypes:
  - preferred_term: Recurrent Respiratory Infections
    term:
      id: HP:0002205
      label: Recurrent respiratory infections
  evidence:
  - reference: PMID:28552099
    reference_title: "Bacteriology and treatment of infections in the upper and lower airways in patients with primary ciliary dyskinesia: adressing the paranasal sinuses."
    supports: SUPPORT
    snippet: Non-functional airway cilia impair the mucociliary clearance (MCC), causing mucostasis, lung infections and destruction, chronic rhinosinusitis (CRS) and hearing impairment. It is of paramount importance to postpone chronic lung infection mainly with Gram-negative bacteria (GNB) in patients with an impaired MCC. When successful, lung function can be stabilized and quality of life (QoL) improved.
    explanation: The literature mentions the importance of postponing chronic lung infection in patients with impaired MCC, which is a characteristic of PCD. This aligns with the use of long-term antibiotic therapy to manage such infections.
  - reference: PMID:26586601
    reference_title: "Treatment recommendations in Primary Ciliary Dyskinesia."
    supports: SUPPORT
    snippet: '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.'
    explanation: The reference states that antibiotic treatment for pulmonary exacerbation is a mainstay of therapy for PCD, supporting the use of long-term or prophylactic antibiotics.
  - reference: PMID:19812481
    reference_title: "Antimicrobial prophylaxis for primary immunodeficiencies."
    supports: SUPPORT
    snippet: Antibiotic prophylaxis is one of the mainstays of therapy of primary immunodeficiencies.
    explanation: While the focus is on primary immunodeficiencies, the principle of using antibiotic prophylaxis can be extended to PCD due to similar needs for managing chronic infections.
  treatment_term:
    preferred_term: antibiotic therapy
    term:
      id: NCIT:C15620
      label: Antibiotic Therapy
- name: Bronchodilators
  description: Medications to help open airways and ease breathing.
  evidence:
  - reference: PMID:36639347
    reference_title: "Primary Ciliary Dyskinesia and Bronchiectasis: New Data and Future Challenges."
    supports: NO_EVIDENCE
    snippet: ''
    explanation: The reference discusses new data and future challenges related to Primary Ciliary Dyskinesia (PCD) and bronchiectasis but does not provide specific information about the use of bronchodilators for PCD.
  - reference: PMID:39269762
    reference_title: "Airway Clearance Techniques in Primary Ciliary Dyskinesia: A Systematic Review."
    supports: NO_EVIDENCE
    snippet: Primary ciliary dyskinesia (PCD) is a respiratory disorder that impairs mucociliary clearance, leading to decreased lung function.
    explanation: The reference focuses on airway clearance techniques in PCD and does not mention the use of bronchodilators.
  - reference: PMID:33507585
    supports: NO_EVIDENCE
    snippet: ''
    explanation: The reference discusses intrapulmonary percussive ventilation for PCD but does not mention bronchodilators.
  - reference: PMID:37449771
    supports: NO_EVIDENCE
    snippet: ''
    explanation: The reference discusses treatment response to pulmonary exacerbation in PCD but does not mention bronchodilators.
  treatment_term:
    preferred_term: bronchodilator therapy
    term:
      id: MAXO:0000316
      label: bronchodilator therapy
- name: Nasal Steroids
  description: Used to treat nasal polyps and chronic sinusitis.
  evidence:
  - reference: PMID:19879441
    reference_title: "Corticosteroid treatment in chronic rhinosinusitis: the possibilities and the limits."
    supports: PARTIAL
    snippet: Long-term treatment with corticosteroid nasal spray reduces inflammation and nasal polyp size, and improves nasal symptoms such as nasal blockage, rhinorrea, and the loss of smell.
    explanation: While nasal steroids are used to treat nasal polyps and chronic rhinosinusitis, the statement should specify that they are used to manage symptoms rather than being a description of Primary Ciliary Dyskinesia (PCD).
  - reference: PMID:33305974
    reference_title: "Exhalation Delivery Systems for Application of Intranasal Corticosteroids."
    supports: PARTIAL
    snippet: Topical nasal steroids play an important role in the treatment of CRS.
    explanation: Nasal steroids are used in the treatment of chronic rhinosinusitis (CRS), which can be a condition associated with PCD. However, the statement should clarify that nasal steroids are for symptom management rather than a direct description of PCD.
  - reference: PMID:35312075
    reference_title: "Chronic Rhinosinusitis: T2r38 Genotyping and Nasal Cytology in Primary Ciliary Dyskinesia."
    supports: PARTIAL
    snippet: Our findings indicate for the first time that PCD patients with CRSwNP display a more severe disease than those with CRSsNP.
    explanation: This reference indicates that chronic rhinosinusitis with nasal polyps (CRSwNP) is more severe in PCD patients. However, it does not directly state that nasal steroids are used to treat these conditions in the context of PCD.
  - reference: PMID:28552099
    reference_title: "Bacteriology and treatment of infections in the upper and lower airways in patients with primary ciliary dyskinesia: adressing the paranasal sinuses."
    supports: PARTIAL
    snippet: Implementing ESS with adjuvant therapy to PCD patients (I, IV) significantly ameliorated CRS symptoms.
    explanation: This reference suggests that surgical and adjuvant therapies, including possibly nasal steroids, can ameliorate CRS symptoms in PCD patients. However, it does not explicitly state the use of nasal steroids.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
- name: Hearing Aids
  description: Assistive devices for hearing loss management.
  evidence:
  - reference: PMID:29287859
    reference_title: "Hearing loss in children with primary ciliary dyskinesia."
    supports: NO_EVIDENCE
    snippet: 'CONCLUSIONS: Slight to mild CHL and all types of otitis media are prevalent among patients with PCD, and some of these children have sensorineural hearing loss (SNHL).'
    explanation: The study discusses the prevalence and types of hearing loss in children with PCD but does not mention the use of hearing aids or other assistive devices for management.
  - reference: PMID:22960754
    reference_title: "Assistive hearing technologies among students with hearing impairment: factors that promote satisfaction."
    supports: NO_EVIDENCE
    snippet: This article explores factors pertaining to children's use of and attitudes toward hearing technologies, such as hearing aids, cochlear implants, teacher-worn microphones, and student-worn microphones.
    explanation: This study focuses on the use of hearing technologies among students with hearing impairment but does not specifically address children with PCD.
  - reference: PMID:28187057
    reference_title: "Improvements in Gait With Hearing Aids and Cochlear Implants."
    supports: NO_EVIDENCE
    snippet: 'OBJECTIVE: To evaluate whether wearing auditory assistive devices can improve gait and dynamic balance.'
    explanation: The study evaluates the impact of hearing assistive devices on gait and balance in adults but does not mention their use in patients with PCD.
  - reference: PMID:30827358
    reference_title: "Medical and Audiological Indications for Implantable Auditory Devices."
    supports: NO_EVIDENCE
    snippet: Implantable auditory devices (IADs) are a viable hearing restoration option for patients with hearing loss.
    explanation: The article discusses implantable auditory devices as a hearing restoration option but does not specifically mention hearing aids for patients with PCD.
  - reference: PMID:2062156
    reference_title: "Primary ciliary dyskinesia and the middle ear."
    supports: NO_EVIDENCE
    snippet: In patients with primary ciliary dyskinesia, a discrepancy was found between subjective ear complaints and the actual middle ear function.
    explanation: This study discusses middle ear function in patients with PCD but does not mention the use of hearing aids or other assistive devices.
  treatment_term:
    preferred_term: supportive care
    term:
      id: MAXO:0000950
      label: supportive care
- name: Genetic Counseling
  description: Provides information and support for affected individuals and families.
  evidence:
  - reference: PMID:29800551
    reference_title: "Advances in the Genetics of Primary Ciliary Dyskinesia: Clinical Implications."
    supports: NO_EVIDENCE
    snippet: Our knowledge of cilia genetics and the function of the proteins encoded has led to a greater understanding of the clinical manifestations of motile ciliopathies. These advances have changed our approach toward diagnostic testing for primary ciliary dyskinesia.
    explanation: The reference discusses advances in genetics and diagnostic testing for primary ciliary dyskinesia but does not mention genetic counseling providing information and support for affected individuals and families.
  - reference: PMID:29905515
    reference_title: "Diagnosis of Primary Ciliary Dyskinesia. An Official American Thoracic Society Clinical Practice Guideline."
    supports: NO_EVIDENCE
    snippet: This document presents the American Thoracic Society clinical practice guidelines for the diagnosis of primary ciliary dyskinesia (PCD).
    explanation: The guideline focuses on diagnostic practices and does not mention genetic counseling or support for affected individuals and families.
  - reference: PMID:19410203
    reference_title: "Primary ciliary dyskinesia: prospects for new therapies, building on the experience in cystic fibrosis."
    supports: NO_EVIDENCE
    snippet: Newer genetic modifiers show an exciting potential for personalized medication, combining selection of patients with a common genetic mutation and a drug treatment that has been specifically designed to overcome that mutation, and will greatly enhance the therapeutic arsenal for PCD.
    explanation: The reference discusses potential future therapies for PCD but does not mention genetic counseling or support services.
  - reference: PMID:35854386
    reference_title: "Clinical and genetic spectrum of primary ciliary dyskinesia in Chinese patients: a systematic review."
    supports: NO_EVIDENCE
    snippet: Diagnostic delay and under-recognition of PCD remain a big issue in China, which contributes to progressive lung disease and PA infection indicating worse outcome.
    explanation: The reference discusses diagnostic delays and clinical outcomes but does not mention genetic counseling or support services.
  treatment_term:
    preferred_term: genetic counseling
    term:
      id: MAXO:0000079
      label: genetic counseling
experimental_models:
- name: Patient-derived nasal epithelial air-liquid interface model
  description: >-
    Expanded basal epithelial cells from nasal brush biopsies re-differentiated
    in miniaturized air-liquid interface cultures to preserve genotype-linked
    ciliary ultrastructural and motility defects in primary ciliary dyskinesia.
  experimental_model_type: PRIMARY_CELL_CULTURE
  namo_type: namo:TwoDCellCulture
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  tissue_term:
    preferred_term: nasal cavity epithelium
    term:
      id: UBERON:0005384
      label: nasal cavity epithelium
  cell_types:
  - preferred_term: respiratory ciliated cell
    term:
      id: CL:0002368
      label: respiratory tract epithelial cell
  conditions:
  - primary ciliary dyskinesia
  - MCIDAS-associated reduced generation of motile cilia
  cell_source: Patient-derived nasal basal epithelial cells expanded from nasal brush biopsies
  culture_system: Miniaturized 96-well Transwell air-liquid interface culture
  publication: PMID:33795320
  findings:
  - statement: Patient-derived nasal ALI cultures retain genotype-linked ciliary ultrastructural and motility defects and can be used to test rescue strategies for reduced multiciliogenesis
    evidence:
    - reference: PMID:33795320
      supports: SUPPORT
      evidence_source: IN_VITRO
      snippet: "Initial analyses of ciliary ultrastructure, beat pattern and beat frequency in the 96-well transwell format ALI cultures indicate that a range of different PCD defects can be retained in these cultures."
      explanation: Supports use of expanded nasal ALI cultures as a disease-relevant PCD model that preserves mutation-associated ciliary defects.
    - reference: PMID:33795320
      supports: SUPPORT
      evidence_source: IN_VITRO
      snippet: "As proof-of-principle, we performed a personalised investigation in a patient with a rare and severe form of PCD (reduced generation of motile cilia), in this case caused by a homozygous nonsense mutation in the MCIDAS gene."
      explanation: Links the ALI model to a mechanistically relevant multiciliogenesis defect within a defined PCD genotype.
  evidence:
  - reference: PMID:33795320
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: "Primary cell culture of basal epithelial cells from nasal brush biopsies followed by ciliated differentiation at the air-liquid interface (ALI) has proven to be a useful tool in PCD diagnostics but the technique's broader utility, including in pre-clinical PCD research, has been restricted by the limited number of basal cells that can be expanded from such biopsies."
    explanation: Establishes patient-derived nasal ALI culture as an existing PCD modeling system and motivates the expanded higher-throughput format.
- name: Patient-derived airway organoid model
  description: >-
    Airway organoids established from nasal inferior turbinate brush samples and
    differentiated toward ciliated cells to capture patient-specific ciliary
    beating abnormalities in primary ciliary dyskinesia.
  experimental_model_type: ORGANOID
  namo_type: namo:Organoid
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  tissue_term:
    preferred_term: nasal cavity epithelium
    term:
      id: UBERON:0005384
      label: nasal cavity epithelium
  cell_types:
  - preferred_term: respiratory ciliated cell
    term:
      id: CL:0002368
      label: respiratory tract epithelial cell
  conditions:
  - primary ciliary dyskinesia
  cell_source: Patient-derived nasal inferior turbinate epithelial cells expanded as airway organoids
  culture_system: Long-term expandable airway organoid culture with ciliated differentiation
  publication: PMID:34693619
  findings:
  - statement: Patient-derived airway organoids reproduce mutation-linked differences in ciliary beating and support genotype-specific functional interrogation
    evidence:
    - reference: PMID:34693619
      supports: SUPPORT
      evidence_source: IN_VITRO
      snippet: "Patient-specific differences in ciliary beating are observed and are in agreement with the patients' genetic mutations."
      explanation: Supports the organoid model as a genotype-resolved readout of the ciliary dysfunction central to PCD.
    - reference: PMID:34693619
      supports: SUPPORT
      evidence_source: IN_VITRO
      snippet: "More detailed organoid ciliary phenotypes can thus be documented in addition to the standard diagnostic procedure."
      explanation: Supports use of organoids for mechanistically richer ciliary phenotyping in PCD.
  evidence:
  - reference: PMID:34693619
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: "We apply this condition to AOs established from nasal inferior turbinate brush samples of patients suffering from primary ciliary dyskinesia (PCD), a pulmonary disease caused by dysfunction of the motile cilia in the airways."
    explanation: Establishes patient-derived airway organoids as a directly disease-relevant non-animal model for PCD.
- name: Patient-specific hiPSC-derived airway epithelium model
  description: >-
    Human induced pluripotent stem cell-derived airway epithelium differentiated
    at air-liquid interface to model structural ciliary defects and impaired
    mucociliary transport in genetically defined primary ciliary dyskinesia.
  experimental_model_type: IPSC_DERIVED_MODEL
  namo_type: namo:TwoDCellCulture
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  tissue_term:
    preferred_term: respiratory airway
    term:
      id: UBERON:0001005
      label: respiratory airway
  cell_types:
  - preferred_term: respiratory ciliated cell
    term:
      id: CL:0002368
      label: respiratory tract epithelial cell
  conditions:
  - primary ciliary dyskinesia
  - DNAH5-associated primary ciliary dyskinesia
  - NME5-associated primary ciliary dyskinesia
  cell_source: Patient-specific induced pluripotent stem cell lines differentiated into ciliated airway epithelium
  culture_system: Air-liquid interface differentiation of hiPSC-derived airway epithelium
  publication: PMID:37296588
  findings:
  - statement: Patient-specific hiPSC-derived airway epithelium reproduces molecular, ultrastructural, and functional ciliary defects, including impaired mucociliary transport
    evidence:
    - reference: PMID:37296588
      supports: SUPPORT
      evidence_source: IN_VITRO
      snippet: "Applying transmission electron microscopy, immunofluorescence staining, ciliary beat frequency, and mucociliary transport measurements, we could demonstrate that ciliated respiratory epithelia cells derived from two PCD patient-specific hiPSC lines carrying mutations in DNAH5 and NME5, respectively, recapitulate the respective diseased phenotype on a molecular, structural and functional level."
      explanation: Shows that hiPSC-derived airway epithelium reproduces the molecular and functional consequences of PCD mutations, including impaired transport.
  evidence:
  - reference: PMID:37296588
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: "Here, we developed an in vitro model for PCD based on human induced pluripotent stem cell (hiPSC)-derived airway epithelium in Air-Liquid-Interface cultures."
    explanation: Establishes hiPSC-derived airway epithelium as a PCD-specific in vitro model.
  - reference: PMID:37296588
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: "Motile cilia dysfunction results in diminished mucociliary clearance (MCC) of pathogens in the respiratory tract and chronic airway inflammation and infections successively causing progressive lung damage."
    explanation: Connects the model's mucociliary transport readouts to the central airway pathophysiology of PCD.
disease_term:
  preferred_term: primary ciliary dyskinesia
  term:
    id: MONDO:0016575
    label: primary ciliary dyskinesia
classifications:
  harrisons_chapter:
  - classification_value: RESPIRATORY
  - classification_value: GENETICS_ENVIRONMENT_DISEASE
  mechanistic_category:
  - classification_value: ciliopathy
references:
- reference: DOI:10.1007/s40291-025-00801-w
  title: 'Clinical, Genetic, Morphological and Functional Correlations in a Large Series of Patients with Primary Ciliary Dyskinesia: A Heterogeneous Disease with a Controversial Diagnosis'
  findings: []
- reference: DOI:10.1183/13993003.01769-2023
  title: Analyses of 1236 genotyped primary ciliary dyskinesia individuals identify regional clusters of distinct DNA variants and significant genotype–phenotype correlations
  findings: []
- reference: DOI:10.1542/peds.2023-063064
  title: Primary Ciliary Dyskinesia
  findings: []
- reference: DOI:10.29057/mjmr.v12i24.12347
  title: 'Exploring In Vitro Models: Advances and Challenges in Human Respiratory Tract Research'
  findings: []
- reference: DOI:10.3390/cells13110974
  title: 'Primary Ciliary Dyskinesia: A Clinical Review'
  findings: []

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References & Deep Research

References

DOI:10.1007/s40291-025-00801-w

Clinical, Genetic, Morphological and Functional Correlations in a Large Series of Patients with Primary Ciliary Dyskinesia: A Heterogeneous Disease with a Controversial Diagnosis