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Primary ciliary dyskinesia 11(CILD11)

MedGen UID:
390741
Concept ID:
C2675229
Disease or Syndrome
Synonyms: CILIARY DYSKINESIA, PRIMARY, 11, WITHOUT SITUS INVERSUS; Primary Ciliary Dyskinesia11: RSPH4A-Related Primary Ciliary Dyskinesia
 
Gene (location): RSPH4A (6q22.1)
 
Monarch Initiative: MONDO:0012978
OMIM®: 612649

Definition

Rarely, individuals with primary ciliary dyskinesia have an accumulation of fluid in the brain (hydrocephalus), likely due to abnormal cilia in the brain.

Another 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.

Primary 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.

Approximately 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.

Some 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.

In 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.

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. [from MedlinePlus Genetics]

Clinical features

From HPO
Exercise intolerance
MedGen UID:
603270
Concept ID:
C0424551
Finding
A functional motor deficit where individuals whose responses to the challenges of exercise fail to achieve levels considered normal for their age and gender.
Reduced sperm motility
MedGen UID:
98339
Concept ID:
C0403823
Disease or Syndrome
An abnormal reduction in the mobility of ejaculated sperm.
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
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 bronchitis
MedGen UID:
3084
Concept ID:
C0008677
Disease or Syndrome
Chronic inflammation of the bronchi.
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\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\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\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 sinusitis
MedGen UID:
107919
Concept ID:
C0581354
Disease or Syndrome
A recurrent form of sinusitis.
Immotile cilia
MedGen UID:
383738
Concept ID:
C1855672
Finding
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.
Recurrent respiratory infections
MedGen UID:
812812
Concept ID:
C3806482
Finding
An increased susceptibility to respiratory infections as manifested by a history of recurrent respiratory infections.
Abnormal central microtubular pair morphology of respiratory motile cilia
MedGen UID:
868586
Concept ID:
C4022985
Anatomical Abnormality
A structural anomaly of the two central microtubules of motile cilia with a 9+2 microtubuluar configuration.
Neonatal respiratory distress
MedGen UID:
924182
Concept ID:
C4281993
Finding
Respiratory difficulty as newborn.
Chronic rhinitis
MedGen UID:
3086
Concept ID:
C0008711
Disease or Syndrome
Chronic inflammation of the nasal mucosa.

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
Lucas JS, Alanin MC, Collins S, Harris A, Johansen HK, Nielsen KG, Papon JF, Robinson P, Walker WT
Expert Rev Respir Med 2017 Oct;11(10):779-790. Epub 2017 Aug 2 doi: 10.1080/17476348.2017.1360770. PMID: 28745925

Recent clinical studies

Etiology

Mei M, Dai D, Guo Z, Zhang C, Liu J, Qi Y, Wang X, Wang L, Qian L
Pediatr Pulmonol 2023 Jun;58(6):1674-1682. Epub 2023 Mar 21 doi: 10.1002/ppul.26374. PMID: 36919525
Kinghorn B, Rosenfeld M, Sullivan E, Onchiri F, Ferkol TW, Sagel SD, Dell SD, Milla C, Shapiro AJ, Sullivan KM, Zariwala MA, Pittman JE, Mollica F, Tiddens HAWM, Kemner-van de Corput M, Knowles MR, Davis SD, Leigh MW
Ann Am Thorac Soc 2023 Apr;20(4):539-547. doi: 10.1513/AnnalsATS.202206-524OC. PMID: 36442147Free 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
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
Lucas JS, Alanin MC, Collins S, Harris A, Johansen HK, Nielsen KG, Papon JF, Robinson P, Walker WT
Expert Rev Respir Med 2017 Oct;11(10):779-790. Epub 2017 Aug 2 doi: 10.1080/17476348.2017.1360770. PMID: 28745925

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
Mei M, Dai D, Guo Z, Zhang C, Liu J, Qi Y, Wang X, Wang L, Qian L
Pediatr Pulmonol 2023 Jun;58(6):1674-1682. Epub 2023 Mar 21 doi: 10.1002/ppul.26374. PMID: 36919525
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
Lucas JS, Alanin MC, Collins S, Harris A, Johansen HK, Nielsen KG, Papon JF, Robinson P, Walker WT
Expert Rev Respir Med 2017 Oct;11(10):779-790. Epub 2017 Aug 2 doi: 10.1080/17476348.2017.1360770. PMID: 28745925
Piatti G, De Santi MM, Torretta S, Pignataro L, Soi D, Ambrosetti U
Ann Otol Rhinol Laryngol 2017 Apr;126(4):322-327. Epub 2017 Feb 12 doi: 10.1177/0003489417691299. PMID: 28290230

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
Kobbernagel HE, Buchvald FF, Haarman EG, Casaulta C, Collins SA, Hogg C, Kuehni CE, Lucas JS, Moser CE, Quittner AL, Raidt J, Rosthøj S, Sørensen AL, Thomsen K, Werner C, Omran H, Nielsen KG
Lancet Respir Med 2020 May;8(5):493-505. doi: 10.1016/S2213-2600(20)30058-8. PMID: 32380069
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
Davis SD, Rosenfeld M, Lee HS, Ferkol TW, Sagel SD, Dell SD, Milla C, Pittman JE, Shapiro AJ, Sullivan KM, Nykamp KR, Krischer JP, Zariwala MA, Knowles MR, Leigh MW
Am J Respir Crit Care Med 2019 Jan 15;199(2):190-198. doi: 10.1164/rccm.201803-0548OC. PMID: 30067075Free PMC Article
Lucas JS, Alanin MC, Collins S, Harris A, Johansen HK, Nielsen KG, Papon JF, Robinson P, Walker WT
Expert Rev Respir Med 2017 Oct;11(10):779-790. Epub 2017 Aug 2 doi: 10.1080/17476348.2017.1360770. PMID: 28745925

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
Kinghorn B, Rosenfeld M, Sullivan E, Onchiri F, Ferkol TW, Sagel SD, Dell SD, Milla C, Shapiro AJ, Sullivan KM, Zariwala MA, Pittman JE, Mollica F, Tiddens HAWM, Kemner-van de Corput M, Knowles MR, Davis SD, Leigh MW
Ann Am Thorac Soc 2023 Apr;20(4):539-547. doi: 10.1513/AnnalsATS.202206-524OC. PMID: 36442147Free 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
Davis SD, Rosenfeld M, Lee HS, Ferkol TW, Sagel SD, Dell SD, Milla C, Pittman JE, Shapiro AJ, Sullivan KM, Nykamp KR, Krischer JP, Zariwala MA, Knowles MR, Leigh MW
Am J Respir Crit Care Med 2019 Jan 15;199(2):190-198. doi: 10.1164/rccm.201803-0548OC. PMID: 30067075Free PMC Article
Lucas JS, Alanin MC, Collins S, Harris A, Johansen HK, Nielsen KG, Papon JF, Robinson P, Walker WT
Expert Rev Respir Med 2017 Oct;11(10):779-790. Epub 2017 Aug 2 doi: 10.1080/17476348.2017.1360770. PMID: 28745925

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
Horani A, Gupta DK, Xu J, Xu H, Carmen Puga-Molina LD, Santi CM, Ramagiri S, Brennan SK, Pan J, Koenitzer JR, Huang T, Hyland RM, Gunsten SP, Tzeng SC, Strahle JM, Mill P, Mahjoub MR, Dutcher SK, Brody SL
JCI Insight 2023 Jun 8;8(11) doi: 10.1172/jci.insight.168836. PMID: 37104040Free 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
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
Leigh MW, Pittman JE, Carson JL, Ferkol TW, Dell SD, Davis SD, Knowles MR, Zariwala MA
Genet Med 2009 Jul;11(7):473-87. doi: 10.1097/GIM.0b013e3181a53562. PMID: 19606528Free PMC Article

Recent systematic reviews

Collins SA, Gove K, Walker W, Lucas JS
Eur Respir J 2014 Dec;44(6):1589-99. Epub 2014 Oct 16 doi: 10.1183/09031936.00088614. PMID: 25323224

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