U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Primary ciliary dyskinesia 21(CILD21)

MedGen UID:
815417
Concept ID:
C3809087
Disease or Syndrome
Synonym: CILIARY DYSKINESIA, PRIMARY, 21, WITHOUT SITUS INVERSUS
 
Gene (location): DRC1 (2p23.3)
 
Monarch Initiative: MONDO:0014123
OMIM®: 615294

Definition

Primary ciliary dyskinesia-21 (CILD21) is an autosomal recessive ciliopathy characterized by infantile onset of chronic sinopulmonary infections resulting from abnormal ciliary function. Electron microscopy of respiratory epithelial cells shows normal outer and inner dynein arms, but absence of nexin links and defects in the nexin-dynein regulatory complex (N-DRC). Video microscopy of patient cilia shows an increased beat frequency with decreased bending amplitude (summary by Wirschell et al., 2013). For a phenotypic description and a discussion of genetic heterogeneity of primary ciliary dyskinesia, see CILD1 (244400). [from OMIM]

Clinical features

From HPO
Atelectasis
MedGen UID:
13946
Concept ID:
C0004144
Pathologic Function
Collapse of part of a lung associated with absence of inflation (air) of that part.
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.
Primary ciliary dyskinesia
MedGen UID:
3467
Concept ID:
C0008780
Disease or Syndrome
Primary ciliary dyskinesia is a disorder characterized by chronic respiratory tract infections, abnormally positioned internal organs, and the inability to have children (infertility). The signs and symptoms of this condition are caused by abnormal cilia and flagella. Cilia are microscopic, finger-like projections that stick out from the surface of cells. They are found in the linings of the airway, the reproductive system, and other organs and tissues. Flagella are tail-like structures, similar to cilia, that propel sperm cells forward.\n\nIn the respiratory tract, cilia move back and forth in a coordinated way to move mucus towards the throat. This movement of mucus helps to eliminate fluid, bacteria, and particles from the lungs. Most babies with primary ciliary dyskinesia experience breathing problems at birth, which suggests that cilia play an important role in clearing fetal fluid from the lungs. Beginning in early childhood, affected individuals develop frequent respiratory tract infections. Without properly functioning cilia in the airway, bacteria remain in the respiratory tract and cause infection. People with primary ciliary dyskinesia also have year-round nasal congestion and a chronic cough. Chronic respiratory tract infections can result in a condition called bronchiectasis, which damages the passages, called bronchi, leading from the windpipe to the lungs and can cause life-threatening breathing problems.\n\nSome individuals with primary ciliary dyskinesia have abnormally placed organs within their chest and abdomen. These abnormalities arise early in embryonic development when the differences between the left and right sides of the body are established. About 50 percent of people with primary ciliary dyskinesia have a mirror-image reversal of their internal organs (situs inversus totalis). For example, in these individuals the heart is on the right side of the body instead of on the left. Situs inversus totalis does not cause any apparent health problems. When someone with primary ciliary dyskinesia has situs inversus totalis, they are often said to have Kartagener syndrome.\n\nApproximately 12 percent of people with primary ciliary dyskinesia have a condition known as heterotaxy syndrome or situs ambiguus, which is characterized by abnormalities of the heart, liver, intestines, or spleen. These organs may be structurally abnormal or improperly positioned. In addition, affected individuals may lack a spleen (asplenia) or have multiple spleens (polysplenia). Heterotaxy syndrome results from problems establishing the left and right sides of the body during embryonic development. The severity of heterotaxy varies widely among affected individuals.\n\nPrimary ciliary dyskinesia can also lead to infertility. Vigorous movements of the flagella are necessary to propel the sperm cells forward to the female egg cell. Because their sperm do not move properly, males with primary ciliary dyskinesia are usually unable to father children. Infertility occurs in some affected females and is likely due to abnormal cilia in the fallopian tubes.\n\nAnother feature of primary ciliary dyskinesia is recurrent ear infections (otitis media), especially in young children. Otitis media can lead to permanent hearing loss if untreated. The ear infections are likely related to abnormal cilia within the inner ear.\n\nRarely, individuals with primary ciliary dyskinesia have an accumulation of fluid in the brain (hydrocephalus), likely due to abnormal cilia in the brain.
Recurrent pneumonia
MedGen UID:
195802
Concept ID:
C0694550
Disease or Syndrome
An increased susceptibility to pneumonia as manifested by a history of recurrent episodes of pneumonia.
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.
Neonatal respiratory distress
MedGen UID:
924182
Concept ID:
C4281993
Finding
Respiratory difficulty as newborn.
Chronic sinusitis
MedGen UID:
101751
Concept ID:
C0149516
Disease or Syndrome
A chronic form of sinusitis.
Recurrent otitis media
MedGen UID:
155436
Concept ID:
C0747085
Disease or Syndrome
Increased susceptibility to otitis media, as manifested by recurrent episodes of otitis media.

Term Hierarchy

Professional guidelines

PubMed

Barber AT, Shapiro AJ, Davis SD, Ferkol TW, Atkinson JJ, Sagel SD, Dell SD, Olivier KN, Milla CE, Rosenfeld M, Li L, Lin FC, Sullivan KM, Capps NA, Zariwala MA, Knowles MR, Leigh MW
Ann Am Thorac Soc 2023 Mar;20(3):397-405. doi: 10.1513/AnnalsATS.202206-487OC. PMID: 36342963Free PMC Article
Dąbkowska S, Kucińska-Chahwan A, Beneturska A, Ilnicka A, Nowakowska B, Panek G, Roszkowski T, Bijok J
Prenat Diagn 2020 Apr;40(5):612-617. Epub 2020 Feb 12 doi: 10.1002/pd.5654. PMID: 32003477
Lobo LJ, Zariwala MA, Noone PG
QJM 2014 Sep;107(9):691-9. Epub 2014 Mar 19 doi: 10.1093/qjmed/hcu063. PMID: 24652656

Recent clinical studies

Etiology

Oh J, Lee JS, Park MS, Kang YA, Cho HJ, Kim SY, Jung J, Yoon SO, Kim KW
Yonsei Med J 2024 Jan;65(1):48-54. doi: 10.3349/ymj.2023.0238. PMID: 38154480Free PMC Article
Barber AT, Shapiro AJ, Davis SD, Ferkol TW, Atkinson JJ, Sagel SD, Dell SD, Olivier KN, Milla CE, Rosenfeld M, Li L, Lin FC, Sullivan KM, Capps NA, Zariwala MA, Knowles MR, Leigh MW
Ann Am Thorac Soc 2023 Mar;20(3):397-405. doi: 10.1513/AnnalsATS.202206-487OC. PMID: 36342963Free PMC Article
Kos R, Israëls J, van Gogh CDL, Altenburg J, Diepenhorst S, Paff T, Boon EMJ, Micha D, Pals G, Neerincx AH, Maitland-van der Zee AH, Haarman EG; Amsterdam Mucociliary Clearance Disease (AMCD) Research Group
Am J Med Genet C Semin Med Genet 2022 Mar;190(1):89-101. Epub 2022 Mar 27 doi: 10.1002/ajmg.c.31968. PMID: 35343062Free PMC Article
Demir Eksi D, Yilmaz E, Basaran AE, Erduran G, Nur B, Mihci E, Karadag B, Bingol A, Alper OM
Indian J Pediatr 2022 Jul;89(7):682-691. Epub 2022 Mar 3 doi: 10.1007/s12098-022-04098-z. PMID: 35239159
Guan Y, Yang H, Yao X, Xu H, Liu H, Tang X, Hao C, Zhang X, Zhao S, Ge W, Ni X
Chest 2021 May;159(5):1768-1781. Epub 2021 Feb 10 doi: 10.1016/j.chest.2021.02.006. PMID: 33577779Free PMC Article

Diagnosis

Oh J, Lee JS, Park MS, Kang YA, Cho HJ, Kim SY, Jung J, Yoon SO, Kim KW
Yonsei Med J 2024 Jan;65(1):48-54. doi: 10.3349/ymj.2023.0238. PMID: 38154480Free PMC Article
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
Zawawi F, Shapiro AJ, Dell S, Wolter NE, Marchica CL, Knowles MR, Zariwala MA, Leigh MW, Smith M, Gajardo P, Daniel SJ
Otolaryngol Head Neck Surg 2022 Mar;166(3):540-547. Epub 2021 Jun 22 doi: 10.1177/01945998211019320. PMID: 34154450Free PMC Article
Guan Y, Yang H, Yao X, Xu H, Liu H, Tang X, Hao C, Zhang X, Zhao S, Ge W, Ni X
Chest 2021 May;159(5):1768-1781. Epub 2021 Feb 10 doi: 10.1016/j.chest.2021.02.006. PMID: 33577779Free PMC Article
Lobo LJ, Zariwala MA, Noone PG
QJM 2014 Sep;107(9):691-9. Epub 2014 Mar 19 doi: 10.1093/qjmed/hcu063. PMID: 24652656

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
Güney E, Emiralioğlu N, Cinel G, Yalçın E, Doğru D, Kiper N, Özçelik HU
Turk J Pediatr 2019;61(1):20-25. doi: 10.24953/turkjped.2019.01.004. PMID: 31559717
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
Frommer A, Hjeij R, Loges NT, Edelbusch C, Jahnke C, Raidt J, Werner C, Wallmeier J, Große-Onnebrink J, Olbrich H, Cindrić S, Jaspers M, Boon M, Memari Y, Durbin R, Kolb-Kokocinski A, Sauer S, Marthin JK, Nielsen KG, Amirav I, Elias N, Kerem E, Shoseyov D, Haeffner K, Omran H
Am J Respir Cell Mol Biol 2015 Oct;53(4):563-73. doi: 10.1165/rcmb.2014-0483OC. PMID: 25789548Free PMC Article
Lobo LJ, Zariwala MA, Noone PG
QJM 2014 Sep;107(9):691-9. Epub 2014 Mar 19 doi: 10.1093/qjmed/hcu063. PMID: 24652656

Prognosis

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
Halbeisen FS, Pedersen ESL, Goutaki M, Spycher BD, Amirav I, Boon M, Cohen-Cymberknoh M, Crowley S, Emiralioglu N, Haarman EG, Karadag B, Koerner-Rettberg C, Latzin P, Loebinger MR, Lucas JS, Mazurek H, Morgan L, Marthin J, Pohunek P, Santamaria F, Schwerk N, Thouvenin G, Yiallouros P, Nielsen KG, Kuehni CE
Eur Respir J 2022 Oct;60(4) Epub 2022 Oct 20 doi: 10.1183/13993003.01918-2021. PMID: 35301251Free PMC Article
Suzaki I, Hirano K, Arai S, Maruyama Y, Mizuyoshi T, Tokudome T, Fujii N, Kobayashi H
Am J Case Rep 2020 Aug 30;21:e923270. doi: 10.12659/AJCR.923270. PMID: 32862191Free PMC Article
Leigh MW, Ferkol TW, Davis SD, Lee HS, Rosenfeld M, Dell SD, Sagel SD, Milla C, Olivier KN, Sullivan KM, Zariwala MA, Pittman JE, Shapiro AJ, Carson JL, Krischer J, Hazucha MJ, Knowles MR
Ann Am Thorac Soc 2016 Aug;13(8):1305-13. doi: 10.1513/AnnalsATS.201511-748OC. PMID: 27070726Free PMC Article
Coutton C, Escoffier J, Martinez G, Arnoult C, Ray PF
Hum Reprod Update 2015 Jul-Aug;21(4):455-85. Epub 2015 Apr 17 doi: 10.1093/humupd/dmv020. PMID: 25888788

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
Halbeisen FS, Pedersen ESL, Goutaki M, Spycher BD, Amirav I, Boon M, Cohen-Cymberknoh M, Crowley S, Emiralioglu N, Haarman EG, Karadag B, Koerner-Rettberg C, Latzin P, Loebinger MR, Lucas JS, Mazurek H, Morgan L, Marthin J, Pohunek P, Santamaria F, Schwerk N, Thouvenin G, Yiallouros P, Nielsen KG, Kuehni CE
Eur Respir J 2022 Oct;60(4) Epub 2022 Oct 20 doi: 10.1183/13993003.01918-2021. PMID: 35301251Free PMC Article
Zawawi F, Shapiro AJ, Dell S, Wolter NE, Marchica CL, Knowles MR, Zariwala MA, Leigh MW, Smith M, Gajardo P, Daniel SJ
Otolaryngol Head Neck Surg 2022 Mar;166(3):540-547. Epub 2021 Jun 22 doi: 10.1177/01945998211019320. PMID: 34154450Free PMC Article
Guan Y, Yang H, Yao X, Xu H, Liu H, Tang X, Hao C, Zhang X, Zhao S, Ge W, Ni X
Chest 2021 May;159(5):1768-1781. Epub 2021 Feb 10 doi: 10.1016/j.chest.2021.02.006. PMID: 33577779Free PMC Article
Leigh MW, Ferkol TW, Davis SD, Lee HS, Rosenfeld M, Dell SD, Sagel SD, Milla C, Olivier KN, Sullivan KM, Zariwala MA, Pittman JE, Shapiro AJ, Carson JL, Krischer J, Hazucha MJ, Knowles MR
Ann Am Thorac Soc 2016 Aug;13(8):1305-13. doi: 10.1513/AnnalsATS.201511-748OC. PMID: 27070726Free PMC Article

Recent systematic reviews

Inaba A, Furuhata M, Morimoto K, Rahman M, Takahashi O, Hijikata M, Knowles MR, Keicho N
BMC Pulm Med 2019 Jul 25;19(1):135. doi: 10.1186/s12890-019-0897-4. PMID: 31345208Free PMC Article
Brower KS, Del Vecchio MT, Aronoff SC
BMC Pediatr 2014 Dec 10;14:4. doi: 10.1186/s12887-014-0299-y. PMID: 25492164Free PMC Article

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Recent activity

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...