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Primary ciliary dyskinesia 13(CILD13)

MedGen UID:
413399
Concept ID:
C2750790
Disease or Syndrome
Synonyms: CILIARY DYSKINESIA, PRIMARY, 13, WITH OR WITHOUT SITUS INVERSUS; Primary Ciliary Dyskinesia13: DNAAF1-Related Primary Ciliary Dyskinesia
 
Gene (location): DNAAF1 (16q24.1)
 
Monarch Initiative: MONDO:0013174
OMIM®: 613193

Definition

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.

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.

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.

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.

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.

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

Clinical features

From HPO
Infertility disorder
MedGen UID:
43876
Concept ID:
C0021359
Finding
Inability to conceive for at least one year after trying and having unprotected sex. Causes of female infertility include endometriosis, fallopian tubes obstruction, and polycystic ovary syndrome. Causes of male infertility include abnormal sperm production or function, blockage of the epididymis, blockage of the ejaculatory ducts, hypospadias, exposure to pesticides, and health related issues.
Situs inversus
MedGen UID:
1642262
Concept ID:
C4551493
Congenital Abnormality
A left-right reversal (or mirror reflection) of the anatomical location of the major thoracic and abdominal organs.
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 sinusitis
MedGen UID:
107919
Concept ID:
C0581354
Disease or Syndrome
A recurrent form of sinusitis.
Recurrent bronchitis
MedGen UID:
148159
Concept ID:
C0741796
Disease or Syndrome
An increased susceptibility to bronchitis as manifested by a history of recurrent bronchitis.
Immotile cilia
MedGen UID:
383738
Concept ID:
C1855672
Finding
Absent inner dynein arms
MedGen UID:
868589
Concept ID:
C4022988
Finding
Absence of the inner dynein arms of respiratory motile cilia, which normally are situated within the peripheral microtubules of motile cilia. This feature is usually appreciated by electron microscopy.
Absent outer dynein arms
MedGen UID:
868590
Concept ID:
C4022989
Finding
Absence of the outer dynein arms of respiratory motile cilia, which normally are situated outside of the peripheral microtubules of motile cilia. This feature is usually appreciated by electron microscopy.
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

Peng B, Gao YH, Xie JQ, He XW, Wang CC, Xu JF, Zhang GJ
Orphanet J Rare Dis 2022 Jul 19;17(1):283. doi: 10.1186/s13023-022-02427-1. PMID: 35854386Free 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
Jaffe BF
Clin Pediatr (Phila) 1974 Nov;13(11):944-8. doi: 10.1177/000992287401301106. PMID: 4138636

Recent clinical studies

Etiology

Roach JC, Glusman G, Smit AF, Huff CD, Hubley R, Shannon PT, Rowen L, Pant KP, Goodman N, Bamshad M, Shendure J, Drmanac R, Jorde LB, Hood L, Galas DJ
Science 2010 Apr 30;328(5978):636-9. Epub 2010 Mar 10 doi: 10.1126/science.1186802. PMID: 20220176Free PMC Article
Indinnimeo L, Tancredi G, Barreto M, De Castro G, Zicari AM, Monaco F, Duse M
Int J Immunopathol Pharmacol 2007 Oct-Dec;20(4):841-5. doi: 10.1177/039463200702000422. PMID: 18179758
Arnal JF, Flores P, Rami J, Murris-Espin M, Bremont F, Pasto I Aguilla M, Serrano E, Didier A
Eur Respir J 1999 Feb;13(2):307-12. doi: 10.1034/j.1399-3003.1999.13b15.x. PMID: 10065673
Konrad F, Schiener R, Marx T, Georgieff M
Intensive Care Med 1995 Jun;21(6):482-9. doi: 10.1007/BF01706201. PMID: 7560491
Wakefield S, Waite D
Am Rev Respir Dis 1980 Jun;121(6):1003-10. doi: 10.1164/arrd.1980.121.6.1003. PMID: 6968169

Diagnosis

Despotes KA, Zariwala MA, Davis SD, Ferkol TW
Cells 2024 Jun 4;13(11) doi: 10.3390/cells13110974. PMID: 38891105Free 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
Society for Maternal-Fetal Medicine, Rac MWF, McKinney J, Gandhi M
Am J Obstet Gynecol 2019 Dec;221(6):B13-B15. doi: 10.1016/j.ajog.2019.09.023. PMID: 31787158
Juvet SC, Hwang D, Downey GP
Can Respir J 2006 Oct;13(7):375-80. doi: 10.1155/2006/696573. PMID: 17036091Free PMC Article
Hamberger L, Lundin K, Sjögren A, Söderlund B
Hum Reprod 1998 Apr;13 Suppl 1:128-33. doi: 10.1093/humrep/13.suppl_1.128. PMID: 9663777

Therapy

Jiang S, Chen H, Shen P, Zhou Y, Li Q, Zhang J, Chen Y
Antioxid Redox Signal 2024 Jan;40(1-3):168-185. Epub 2023 Dec 8 doi: 10.1089/ars.2023.0410. PMID: 37917094
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
Lundberg JO, Nordvall SL, Weitzberg E, Kollberg H, Alving K
Arch Dis Child 1996 Oct;75(4):323-6. doi: 10.1136/adc.75.4.323. PMID: 8984919Free PMC Article
Desai M, Weller PH, Spencer DA
Pediatr Pulmonol 1995 Nov;20(5):307-8. doi: 10.1002/ppul.1950200509. PMID: 8903903
Konrad F, Schiener R, Marx T, Georgieff M
Intensive Care Med 1995 Jun;21(6):482-9. doi: 10.1007/BF01706201. PMID: 7560491

Prognosis

Jiang S, Chen H, Shen P, Zhou Y, Li Q, Zhang J, Chen Y
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Sagel SD, Kupfer O, Wagner BD, Davis SD, Dell SD, Ferkol TW, Hoppe JE, Rosenfeld M, Sullivan KM, Tiddens HAWM, Knowles MR, Leigh MW
Ann Am Thorac Soc 2023 Jan;20(1):67-74. doi: 10.1513/AnnalsATS.202204-314OC. PMID: 35984413Free PMC Article
Society for Maternal-Fetal Medicine, Rac MWF, McKinney J, Gandhi M
Am J Obstet Gynecol 2019 Dec;221(6):B13-B15. doi: 10.1016/j.ajog.2019.09.023. PMID: 31787158
Indinnimeo L, Tancredi G, Barreto M, De Castro G, Zicari AM, Monaco F, Duse M
Int J Immunopathol Pharmacol 2007 Oct-Dec;20(4):841-5. doi: 10.1177/039463200702000422. PMID: 18179758
Juvet SC, Hwang D, Downey GP
Can Respir J 2006 Oct;13(7):375-80. doi: 10.1155/2006/696573. PMID: 17036091Free PMC Article

Clinical prediction guides

Jiang S, Chen H, Shen P, Zhou Y, Li Q, Zhang J, Chen Y
Antioxid Redox Signal 2024 Jan;40(1-3):168-185. Epub 2023 Dec 8 doi: 10.1089/ars.2023.0410. PMID: 37917094
Sagel SD, Kupfer O, Wagner BD, Davis SD, Dell SD, Ferkol TW, Hoppe JE, Rosenfeld M, Sullivan KM, Tiddens HAWM, Knowles MR, Leigh MW
Ann Am Thorac Soc 2023 Jan;20(1):67-74. doi: 10.1513/AnnalsATS.202204-314OC. PMID: 35984413Free PMC Article
Barisic I, Boban L, Loane M, Garne E, Wellesley D, Calzolari E, Dolk H, Addor MC, Bergman JE, Braz P, Draper ES, Haeusler M, Khoshnood B, Klungsoyr K, Pierini A, Queisser-Luft A, Rankin J, Rissmann A, Verellen-Dumoulin C
Eur J Hum Genet 2015 Jun;23(6):746-52. Epub 2014 Sep 3 doi: 10.1038/ejhg.2014.174. PMID: 25182137Free PMC Article
Arnal JF, Flores P, Rami J, Murris-Espin M, Bremont F, Pasto I Aguilla M, Serrano E, Didier A
Eur Respir J 1999 Feb;13(2):307-12. doi: 10.1034/j.1399-3003.1999.13b15.x. PMID: 10065673
Desai M, Weller PH, Spencer DA
Pediatr Pulmonol 1995 Nov;20(5):307-8. doi: 10.1002/ppul.1950200509. PMID: 8903903

Recent systematic reviews

Peng B, Gao YH, Xie JQ, He XW, Wang CC, Xu JF, Zhang GJ
Orphanet J Rare Dis 2022 Jul 19;17(1):283. doi: 10.1186/s13023-022-02427-1. PMID: 35854386Free PMC Article
Zhang Y, Song A, Liu J, Dai J, Lin J
J Investig Med 2021 Mar;69(3):742-748. Epub 2020 Dec 3 doi: 10.1136/jim-2020-001479. PMID: 33272932
Adil EA, Kawai K, Dombrowski N, Irace AL, Cunningham MJ
Laryngoscope 2017 Jan;127(1):6-13. Epub 2016 Jun 16 doi: 10.1002/lary.26070. PMID: 27312809

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