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Ciliary dyskinesia, primary, 42(CILD42)

MedGen UID:
1684665
Concept ID:
C5231464
Disease or Syndrome
Synonym: CILIARY DYSKINESIA, PRIMARY, 42, WITHOUT SITUS INVERSUS
 
Gene (location): MCIDAS (5q11.2)
 
Monarch Initiative: MONDO:0032872
OMIM®: 618695

Definition

Primary ciliary dyskinesia-42 (CILD42) is an autosomal recessive disorder characterized by a defect in motile cilia and ciliary clearance resulting in the onset of respiratory insufficiency soon after birth, and associated with recurrent upper and lower respiratory infections with chronic progressive lung disease. Other more variable features may include infertility and mild hydrocephalus. Patients with this form of the disorder do not have situs abnormalities. The disorder is considered to be a type of ciliopathy known as 'reduced generation of multiple motile cilia' (RGMC) (summary by Boon et al., 2014). For a discussion of genetic heterogeneity of primary ciliary dyskinesia, CILD1 (244400). [from OMIM]

Clinical features

From HPO
Bronchiectasis
MedGen UID:
14234
Concept ID:
C0006267
Disease or Syndrome
Persistent abnormal dilatation of the bronchi owing to localized and irreversible destruction and widening of the large airways.
Chronic obstructive pulmonary disease
MedGen UID:
9818
Concept ID:
C0024117
Disease or Syndrome
Chronic obstructive pulmonary disease (COPD) is a common, complex disorder associated with substantial morbidity and mortality. COPD is defined by irreversible airflow obstruction due to chronic bronchitis, emphysema, and/or small airways disease. Airflow obstruction is typically determined by reductions in quantitative spirometric indices, including forced expiratory volume at 1 second (FEV1) and the ratio of FEV1 to forced vital capacity (FVC) (Silverman et al., 2002; Celedon et al., 2004).
Respiratory insufficiency
MedGen UID:
11197
Concept ID:
C0035229
Pathologic Function
Impairment of gas exchange within the lungs secondary to a disease process, neoplasm, or trauma, possibly resulting in hypoxia, hypercarbia, or both, but not requiring intubation or mechanical ventilation. Patients are normally managed with pharmaceutical therapy, supplemental oxygen, or both.
Recurrent sinusitis
MedGen UID:
107919
Concept ID:
C0581354
Disease or Syndrome
A recurrent form of sinusitis.
Reduced forced vital capacity
MedGen UID:
337630
Concept ID:
C1846678
Finding
An abnormal reduction in the amount of air a person can expel following maximal inspiration.
Decreased nasal nitric oxide
MedGen UID:
767344
Concept ID:
C3554430
Finding
Reduced level of nasal nitric oxide (nNO). Current American Thoracic Society/European Respiratory Society (ATS/ERS) guidelines for nNO measurements recommend air aspiration via a nasal probe while the subject exhales through the mouth against resistance in order to maintain velum closure.
Pneumonia
MedGen UID:
10813
Concept ID:
C0032285
Disease or Syndrome
Inflammation of any part of the lung parenchyma.
Chronic rhinitis
MedGen UID:
3086
Concept ID:
C0008711
Disease or Syndrome
Chronic inflammation of the nasal mucosa.
Nasal polyposis
MedGen UID:
6524
Concept ID:
C0027430
Anatomical Abnormality
Polypoidal masses arising mainly from the mucous membranes of the nose and paranasal sinuses. They are freely movable and nontender overgrowths of the mucosa that frequently accompany allergic rhinitis.

Professional guidelines

PubMed

Shoemark A, Harman K
Semin Respir Crit Care Med 2021 Aug;42(4):537-548. Epub 2021 Jul 14 doi: 10.1055/s-0041-1730919. PMID: 34261178
Fassad MR, Patel MP, Shoemark A, Cullup T, Hayward J, Dixon M, Rogers AV, Ollosson S, Jackson C, Goggin P, Hirst RA, Rutman A, Thompson J, Jenkins L, Aurora P, Moya E, Chetcuti P, O'Callaghan C, Morris-Rosendahl DJ, Watson CM, Wilson R, Carr S, Walker W, Pitno A, Lopes S, Morsy H, Shoman W, Pereira L, Constant C, Loebinger MR, Chung EMK, Kenia P, Rumman N, Fasseeh N, Lucas JS, Hogg C, Mitchison HM
J Med Genet 2020 May;57(5):322-330. Epub 2019 Dec 25 doi: 10.1136/jmedgenet-2019-106501. PMID: 31879361
Alanin MC
Dan Med J 2017 May;64(5) PMID: 28552099

Recent clinical studies

Etiology

Spencer S, Donovan T, Chalmers JD, Mathioudakis AG, McDonnell MJ, Tsang A, Leadbetter P
Cochrane Database Syst Rev 2022 Jan 5;1(1):CD013254. doi: 10.1002/14651858.CD013254.pub2. PMID: 34985761Free PMC Article
Guo Z, Chen W, Wang L, Qian L
J Pediatr 2020 Oct;225:157-165.e5. Epub 2020 Jun 2 doi: 10.1016/j.jpeds.2020.05.052. PMID: 32502479
Kreicher KL, Schopper HK, Naik AN, Hatch JL, Meyer TA
Int J Pediatr Otorhinolaryngol 2018 Jan;104:161-165. Epub 2017 Nov 11 doi: 10.1016/j.ijporl.2017.11.005. PMID: 29287859
Abitbul R, Amirav I, Blau H, Alkrinawi S, Aviram M, Shoseyov D, Bentur L, Avital A, Springer C, Lavie M, Prais D, Dabbah H, Elias N, Elizur A, Goldberg S, Hevroni A, Kerem E, Luder A, Roth Y, Cohen-Cymberknoh M, Ben Ami M, Mandelberg A, Livnat G, Picard E, Rivlin J, Rotschild M, Soferman R, Loges NT, Olbrich H, Werner C, Wolter A, Herting M, Wallmeier J, Raidt J, Omran H, Mussaffi H
Respir Med 2016 Oct;119:41-47. Epub 2016 Aug 23 doi: 10.1016/j.rmed.2016.08.015. PMID: 27692146
Santamaria F, Esposito M, Montella S, Cantone E, Mollica C, De Stefano S, Mirra V, Carotenuto M
Respirology 2014 May;19(4):570-5. Epub 2014 Mar 24 doi: 10.1111/resp.12273. PMID: 24661455

Diagnosis

Ringshausen FC, Shapiro AJ, Nielsen KG, Mazurek H, Pifferi M, Donn KH, van der Eerden MM, Loebinger MR, Zariwala MA, Leigh MW, Knowles MR, Ferkol TW; CLEAN-PCD investigators and study team
Lancet Respir Med 2024 Jan;12(1):21-33. Epub 2023 Aug 31 doi: 10.1016/S2213-2600(23)00226-6. PMID: 37660715
Shoemark A, Harman K
Semin Respir Crit Care Med 2021 Aug;42(4):537-548. Epub 2021 Jul 14 doi: 10.1055/s-0041-1730919. PMID: 34261178
Kreicher KL, Schopper HK, Naik AN, Hatch JL, Meyer TA
Int J Pediatr Otorhinolaryngol 2018 Jan;104:161-165. Epub 2017 Nov 11 doi: 10.1016/j.ijporl.2017.11.005. PMID: 29287859
LaDuca H, Farwell KD, Vuong H, Lu HM, Mu W, Shahmirzadi L, Tang S, Chen J, Bhide S, Chao EC
PLoS One 2017;12(2):e0170843. Epub 2017 Feb 2 doi: 10.1371/journal.pone.0170843. PMID: 28152038Free PMC Article
Zariwala MA, Knowles MR, Omran H
Annu Rev Physiol 2007;69:423-50. doi: 10.1146/annurev.physiol.69.040705.141301. PMID: 17059358

Therapy

Ringshausen FC, Shapiro AJ, Nielsen KG, Mazurek H, Pifferi M, Donn KH, van der Eerden MM, Loebinger MR, Zariwala MA, Leigh MW, Knowles MR, Ferkol TW; CLEAN-PCD investigators and study team
Lancet Respir Med 2024 Jan;12(1):21-33. Epub 2023 Aug 31 doi: 10.1016/S2213-2600(23)00226-6. PMID: 37660715
Spencer S, Donovan T, Chalmers JD, Mathioudakis AG, McDonnell MJ, Tsang A, Leadbetter P
Cochrane Database Syst Rev 2022 Jan 5;1(1):CD013254. doi: 10.1002/14651858.CD013254.pub2. PMID: 34985761Free PMC Article
Shoemark A, Harman K
Semin Respir Crit Care Med 2021 Aug;42(4):537-548. Epub 2021 Jul 14 doi: 10.1055/s-0041-1730919. PMID: 34261178
LaDuca H, Farwell KD, Vuong H, Lu HM, Mu W, Shahmirzadi L, Tang S, Chen J, Bhide S, Chao EC
PLoS One 2017;12(2):e0170843. Epub 2017 Feb 2 doi: 10.1371/journal.pone.0170843. PMID: 28152038Free PMC Article
Abitbul R, Amirav I, Blau H, Alkrinawi S, Aviram M, Shoseyov D, Bentur L, Avital A, Springer C, Lavie M, Prais D, Dabbah H, Elias N, Elizur A, Goldberg S, Hevroni A, Kerem E, Luder A, Roth Y, Cohen-Cymberknoh M, Ben Ami M, Mandelberg A, Livnat G, Picard E, Rivlin J, Rotschild M, Soferman R, Loges NT, Olbrich H, Werner C, Wolter A, Herting M, Wallmeier J, Raidt J, Omran H, Mussaffi H
Respir Med 2016 Oct;119:41-47. Epub 2016 Aug 23 doi: 10.1016/j.rmed.2016.08.015. PMID: 27692146

Prognosis

Gut G, Bar-Yoseph R, Hanna M, Brandl N, Alisha I, Rizik S, Pollak M, Hakim F, Amirav I, Bentur L, Gur M
Pediatr Pulmonol 2024 Mar;59(3):688-694. Epub 2023 Dec 20 doi: 10.1002/ppul.26814. PMID: 38116904
Ringshausen FC, Shapiro AJ, Nielsen KG, Mazurek H, Pifferi M, Donn KH, van der Eerden MM, Loebinger MR, Zariwala MA, Leigh MW, Knowles MR, Ferkol TW; CLEAN-PCD investigators and study team
Lancet Respir Med 2024 Jan;12(1):21-33. Epub 2023 Aug 31 doi: 10.1016/S2213-2600(23)00226-6. PMID: 37660715
Spencer S, Donovan T, Chalmers JD, Mathioudakis AG, McDonnell MJ, Tsang A, Leadbetter P
Cochrane Database Syst Rev 2022 Jan 5;1(1):CD013254. doi: 10.1002/14651858.CD013254.pub2. PMID: 34985761Free PMC Article
Guo Z, Chen W, Wang L, Qian L
J Pediatr 2020 Oct;225:157-165.e5. Epub 2020 Jun 2 doi: 10.1016/j.jpeds.2020.05.052. PMID: 32502479
LaDuca H, Farwell KD, Vuong H, Lu HM, Mu W, Shahmirzadi L, Tang S, Chen J, Bhide S, Chao EC
PLoS One 2017;12(2):e0170843. Epub 2017 Feb 2 doi: 10.1371/journal.pone.0170843. PMID: 28152038Free PMC Article

Clinical prediction guides

Ringshausen FC, Shapiro AJ, Nielsen KG, Mazurek H, Pifferi M, Donn KH, van der Eerden MM, Loebinger MR, Zariwala MA, Leigh MW, Knowles MR, Ferkol TW; CLEAN-PCD investigators and study team
Lancet Respir Med 2024 Jan;12(1):21-33. Epub 2023 Aug 31 doi: 10.1016/S2213-2600(23)00226-6. PMID: 37660715
Spencer S, Donovan T, Chalmers JD, Mathioudakis AG, McDonnell MJ, Tsang A, Leadbetter P
Cochrane Database Syst Rev 2022 Jan 5;1(1):CD013254. doi: 10.1002/14651858.CD013254.pub2. PMID: 34985761Free PMC Article
Fabri L, Shanthikumar S, Tadd K, Morgan L, Schultz A, Robinson P
J Paediatr Child Health 2022 Apr;58(4):683-686. Epub 2021 Nov 16 doi: 10.1111/jpc.15818. PMID: 34786797
Guo Z, Chen W, Wang L, Qian L
J Pediatr 2020 Oct;225:157-165.e5. Epub 2020 Jun 2 doi: 10.1016/j.jpeds.2020.05.052. PMID: 32502479
LaDuca H, Farwell KD, Vuong H, Lu HM, Mu W, Shahmirzadi L, Tang S, Chen J, Bhide S, Chao EC
PLoS One 2017;12(2):e0170843. Epub 2017 Feb 2 doi: 10.1371/journal.pone.0170843. PMID: 28152038Free PMC Article

Recent systematic reviews

Spencer S, Donovan T, Chalmers JD, Mathioudakis AG, McDonnell MJ, Tsang A, Leadbetter P
Cochrane Database Syst Rev 2022 Jan 5;1(1):CD013254. doi: 10.1002/14651858.CD013254.pub2. PMID: 34985761Free PMC Article

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