Primary_Ciliary_Dyskinesia

name: Primary_Ciliary_Dyskinesia
creation_date: '2025-12-04T16:57:31Z'
updated_date: '2026-03-31T04:24:13Z'
category: Genetic
parents:
- Ciliopathy
- Respiratory Disease
prevalence:
- population: Global
  percentage: 0.025-0.05
  evidence:
  - reference: PMID:34454779
    reference_title: "Analysis of the clinical features of Japanese patients with primary ciliary dyskinesia."
    supports: PARTIAL
    snippet: Primary ciliary dyskinesia (PCD) is a rare hereditary disease.
    explanation: The study mentions that PCD is a rare disease but does not
      provide specific global prevalence rates.
  - reference: PMID:31971980
    reference_title: "Primary ciliary dyskinesia and psychological well-being in adolescence."
    supports: PARTIAL
    snippet: Primary ciliary dyskinesia (PCD) is a rare autosomal recessive
      disease with low prevalence in pediatrics.
    explanation: The study confirms that PCD is rare but does not provide exact
      global prevalence figures.
  - reference: PMID:32662935
    reference_title: "Phenotypic features of ciliary dyskinesia among patients with congenital cardiovascular malformations."
    supports: PARTIAL
    snippet: Cilia are cell membrane-bound organelles responsible for airway
      mucus clearance, establishment of left-right organ asymmetry,
      cardiogenesis, and many other functions in utero.
    explanation: The study discusses the functions of cilia and mentions ciliary
      dyskinesia but does not provide prevalence data.
  - reference: PMID:30792130
    reference_title: "Primary ciliary dyskinesia among Arabs: Where do we go from here?"
    supports: PARTIAL
    snippet: Primary ciliary dyskinesia (PCD), also known as immotile-cilia
      syndrome, is a rare genetic disease.
    explanation: The study acknowledges that PCD is a rare genetic disease but
      does not specify the global prevalence.
  - reference: PMID:26826908
    reference_title: "Primary Ciliary Dyskinesia."
    supports: NO_EVIDENCE
    snippet: Primary Ciliary Dyskinesia.
    explanation: This reference does not provide information on the global
      prevalence of PCD.
  - reference: PMID:15917207
    reference_title: "Cilia and disease."
    supports: NO_EVIDENCE
    snippet: Cilia are classified according to their microtubule components as
      9+2 (motile) and 9+0 (primary) cilia.
    explanation: This reference discusses cilia and their functions but does not
      provide prevalence data for PCD.
  - 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: This reference focuses on diagnostic guidelines and does not
      provide prevalence data.
  - reference: PMID:31430425
    reference_title: "Prevalence of chronic rhinosinusitis in bronchiectasis patients suspected of ciliary dyskinesia."
    supports: NO_EVIDENCE
    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: This study evaluates CRS in patients suspected of having
      ciliary dyskinesia but does not provide global prevalence data for PCD.
  - reference: PMID:36588099
    reference_title: "Primary ciliary dyskinesia: A multicenter survey on clinical practice and patient management in Italy."
    supports: NO_EVIDENCE
    snippet: There are no recent data on primary ciliary dyskinesia (PCD)
      distribution, diagnosis and treatment in Italy.
    explanation: This reference discusses PCD in Italy but does not provide
      global prevalence data.
pathophysiology:
- name: Ciliary 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: 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: 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: 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: 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: 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: Gastrointestinal
  name: Nasal Polyps
  frequency: FREQUENT
  evidence:
  - 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: OCCASIONAL
  evidence:
  - 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
  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
  phenotype_term:
    preferred_term: Male infertility
    term:
      id: HP:0003251
      label: Male infertility
- category: Respiratory
  name: Chronic Rhinosinusitis
  frequency: VERY_FREQUENT
  notes: Chronic inflammation of nasal passages and sinuses
  phenotype_term:
    preferred_term: Chronic rhinosinusitis
    term:
      id: HP:0011109
      label: Chronic sinusitis
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: 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: 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
- 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
- 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
- name: RSPH1
  association: Pathogenic Variants
  notes: Radial spoke head component coordinating central pair-dynein regulation
- name: RSPH4A
  association: Pathogenic Variants
  notes: Radial spoke protein required for radial spoke integrity and
    coordinated beating
- name: RSPH9
  association: Pathogenic Variants
  notes: Radial spoke head subunit impacting central pair-radial spoke
    interactions
- 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
- name: FOXJ1
  association: Pathogenic Variants
  notes: Master transcription factor regulating motile ciliogenesis; can present
    in autosomal dominant fashion
- name: MCIDAS
  association: Pathogenic Variants
  notes: Drives multiciliated cell differentiation and centriole biogenesis;
    associated with reduced cilia number
- name: ODAD1
  association: Pathogenic Variants
  notes: Outer dynein arm docking/assembly factor; associated with relatively
    milder lung function impact
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: pharmacotherapy
    term:
      id: MAXO:0000058
      label: pharmacotherapy
- 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: pharmacotherapy
    term:
      id: MAXO:0000058
      label: pharmacotherapy
- 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: MAXO:0000058
      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 system disorder
  - classification_value: hereditary 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: []