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Primary ciliary dyskinesia 32(CILD32)

MedGen UID:
896106
Concept ID:
C4225311
Disease or Syndrome
Synonym: CILIARY DYSKINESIA, PRIMARY, 32, WITHOUT SITUS INVERSUS
 
Gene (location): RSPH3 (6q25.3)
 
Monarch Initiative: MONDO:0014657
OMIM®: 616481

Definition

Primary ciliary dyskinesia-32 is an autosomal recessive disorder caused by defective structure and function of cilia. Ciliary dysfunction causes respiratory distress in term neonates, impaired mucociliary clearance, chronic respiratory infections, bronchiectasis, and infertility. The ciliary defect affects the central pair complex and radial spokes of the 9+2 motile cilia; affected individuals do not have situs abnormalities (summary by Jeanson et al., 2015). For a general phenotypic description and a discussion of genetic heterogeneity of primary ciliary dyskinesia, see CILD1 (244400). [from OMIM]

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\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.
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).
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.
Absent respiratory ciliary axoneme radial spokes
MedGen UID:
868582
Concept ID:
C4022981
Finding
Absence of the radial spokes of the axoneme of the respiratory cilium.
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.
Chronic rhinitis
MedGen UID:
3086
Concept ID:
C0008711
Disease or Syndrome
Chronic inflammation of the nasal mucosa.

Term Hierarchy

Professional guidelines

PubMed

Gatt D, Shaw M, Waters V, Kritzinger F, Solomon M, Dell S, Ratjen F
Pediatr Pulmonol 2023 Oct;58(10):2857-2864. Epub 2023 Jul 14 doi: 10.1002/ppul.26599. PMID: 37449771
Goutaki M, Lam YT, Alexandru M, Anagiotos A, Armengot M, Boon M, Burgess A, Caversaccio N, Crowley S, Dheyauldeen SAD, Emiralioglu N, Erdem E, van Gogh C, Gunaydin O, Haarman EG, Harris A, Hayn I, Ismail-Koch H, Karadag B, Kempeneers C, Kim S, Lorent N, Ozcelik U, Pioch C, Poirrier AML, Reula A, Roehmel J, Yiallouros P, Yumusakhuylu AC, Papon JF
JAMA Otolaryngol Head Neck Surg 2023 Jul 1;149(7):587-596. doi: 10.1001/jamaoto.2023.0841. PMID: 37166807Free PMC Article
Lobo J, Zariwala MA, Noone PG
Semin Respir Crit Care Med 2015 Apr;36(2):169-79. Epub 2015 Mar 31 doi: 10.1055/s-0035-1546748. PMID: 25826585Free PMC Article

Recent clinical studies

Etiology

Gatt D, Shaw M, Waters V, Kritzinger F, Solomon M, Dell S, Ratjen F
Pediatr Pulmonol 2023 Oct;58(10):2857-2864. Epub 2023 Jul 14 doi: 10.1002/ppul.26599. PMID: 37449771
Shafiq I, Wahla AS, Uzbeck MH, Zoumot Z, Abuzakouk M, Elkhalifa S, Bodi G, Almazrouei KM, Bodi K, Isse S
BMC Pulm Med 2023 Jul 10;23(1):250. doi: 10.1186/s12890-023-02543-z. PMID: 37430275Free PMC Article
Goutaki M, Lam YT, Alexandru M, Anagiotos A, Armengot M, Boon M, Burgess A, Caversaccio N, Crowley S, Dheyauldeen SAD, Emiralioglu N, Erdem E, van Gogh C, Gunaydin O, Haarman EG, Harris A, Hayn I, Ismail-Koch H, Karadag B, Kempeneers C, Kim S, Lorent N, Ozcelik U, Pioch C, Poirrier AML, Reula A, Roehmel J, Yiallouros P, Yumusakhuylu AC, Papon JF
JAMA Otolaryngol Head Neck Surg 2023 Jul 1;149(7):587-596. doi: 10.1001/jamaoto.2023.0841. PMID: 37166807Free PMC Article
Blanter M, Cockx M, Wittebols L, Abouelasrar Salama S, De Bondt M, Berghmans N, Pörtner N, Vanbrabant L, Lorent N, Gouwy M, Boon M, Struyf S
Respir Res 2022 Dec 17;23(1):359. doi: 10.1186/s12931-022-02280-7. PMID: 36528664Free PMC Article
Nyilas S, Bauman G, Pusterla O, Sommer G, Singer F, Stranzinger E, Heyer C, Ramsey K, Schlegtendal A, Benzrath S, Casaulta C, Goutaki M, Kuehni CE, Bieri O, Koerner-Rettberg C, Latzin P
Ann Am Thorac Soc 2018 Dec;15(12):1434-1442. doi: 10.1513/AnnalsATS.201712-967OC. PMID: 30290127

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
Goutaki M, Lam YT, Alexandru M, Anagiotos A, Armengot M, Boon M, Burgess A, Caversaccio N, Crowley S, Dheyauldeen SAD, Emiralioglu N, Erdem E, van Gogh C, Gunaydin O, Haarman EG, Harris A, Hayn I, Ismail-Koch H, Karadag B, Kempeneers C, Kim S, Lorent N, Ozcelik U, Pioch C, Poirrier AML, Reula A, Roehmel J, Yiallouros P, Yumusakhuylu AC, Papon JF
JAMA Otolaryngol Head Neck Surg 2023 Jul 1;149(7):587-596. doi: 10.1001/jamaoto.2023.0841. PMID: 37166807Free PMC Article
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
Lobo J, Zariwala MA, Noone PG
Semin Respir Crit Care Med 2015 Apr;36(2):169-79. Epub 2015 Mar 31 doi: 10.1055/s-0035-1546748. PMID: 25826585Free PMC Article
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

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
Gatt D, Shaw M, Waters V, Kritzinger F, Solomon M, Dell S, Ratjen F
Pediatr Pulmonol 2023 Oct;58(10):2857-2864. Epub 2023 Jul 14 doi: 10.1002/ppul.26599. PMID: 37449771
Lobo J, Zariwala MA, Noone PG
Semin Respir Crit Care Med 2015 Apr;36(2):169-79. Epub 2015 Mar 31 doi: 10.1055/s-0035-1546748. PMID: 25826585Free PMC Article
Campbell R
Curr Opin Allergy Clin Immunol 2012 Feb;12(1):32-8. doi: 10.1097/ACI.0b013e32834eccc6. PMID: 22157161
Prulière-Escabasse V, Coste A, Chauvin P, Fauroux B, Tamalet A, Garabedian EN, Escudier E, Roger G
Arch Otolaryngol Head Neck Surg 2010 Nov;136(11):1121-6. doi: 10.1001/archoto.2010.183. PMID: 21079168Free PMC Article

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
Gatt D, Shaw M, Waters V, Kritzinger F, Solomon M, Dell S, Ratjen F
Pediatr Pulmonol 2023 Oct;58(10):2857-2864. Epub 2023 Jul 14 doi: 10.1002/ppul.26599. PMID: 37449771
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
Takeuchi K, Kitano M, Sakaida H, Usui S, Masuda S, Ogawa S, Ikejiri M, Nagao M, Fujisawa T, Nakatani K
Otol Neurotol 2017 Dec;38(10):e451-e456. doi: 10.1097/MAO.0000000000001599. PMID: 29135867
Lobo J, Zariwala MA, Noone PG
Semin Respir Crit Care Med 2015 Apr;36(2):169-79. Epub 2015 Mar 31 doi: 10.1055/s-0035-1546748. PMID: 25826585Free 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
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
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
Hjeij R, Onoufriadis A, Watson CM, Slagle CE, Klena NT, Dougherty GW, Kurkowiak M, Loges NT, Diggle CP, Morante NF, Gabriel GC, Lemke KL, Li Y, Pennekamp P, Menchen T, Konert F, Marthin JK, Mans DA, Letteboer SJ, Werner C, Burgoyne T, Westermann C, Rutman A, Carr IM, O'Callaghan C, Moya E, Chung EM; UK10K Consortium, Sheridan E, Nielsen KG, Roepman R, Bartscherer K, Burdine RD, Lo CW, Omran H, Mitchison HM
Am J Hum Genet 2014 Sep 4;95(3):257-74. doi: 10.1016/j.ajhg.2014.08.005. PMID: 25192045Free PMC Article
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

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
Kouis P, Yiallouros PK, Middleton N, Evans JS, Kyriacou K, Papatheodorou SI
Pediatr Res 2017 Mar;81(3):398-405. Epub 2016 Dec 9 doi: 10.1038/pr.2016.263. PMID: 27935903

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