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Primary ciliary dyskinesia 3(CILD3)

MedGen UID:
325210
Concept ID:
C1837618
Disease or Syndrome
Synonym: Primary Ciliary Dyskinesia 3: DNAH5-Related Primary Ciliary Dyskinesia
 
Gene (location): DNAH5 (5p15.2)
 
Monarch Initiative: MONDO:0012085
OMIM®: 608644

Definition

Primary ciliary dyskinesia (PCD; CILD) is an autosomal recessive disorder resulting from loss of normal ciliary function. Kartagener (pronounced KART-agayner) syndrome is characterized by the combination of primary ciliary dyskinesia and situs inversus, and occurs in approximately half of patients with ciliary dyskinesia. Since normal nodal ciliary movement in the embryo is required for normal visceral asymmetry, absence of normal ciliary movement results in a lack of definitive patterning; thus, random chance alone appears to determine whether the viscera take up the normal or reversed left-right position during embryogenesis. This explains why approximately 50% of patients, even within the same family, have situs inversus (summary by Afzelius, 1976; El Zein et al., 2003). For a general phenotypic description and a discussion of genetic heterogeneity of primary ciliary dyskinesia and the Kartagener syndrome, see CILD1 (244400). [from OMIM]

Additional description

From MedlinePlus Genetics
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.

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.

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.

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.  https://medlineplus.gov/genetics/condition/primary-ciliary-dyskinesia

Clinical features

From HPO
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.
Recurrent sinusitis
MedGen UID:
107919
Concept ID:
C0581354
Disease or Syndrome
A recurrent form of sinusitis.
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.
Neonatal respiratory distress
MedGen UID:
924182
Concept ID:
C4281993
Finding
Respiratory difficulty as newborn.
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

Pioch CO, Connell DW, Shoemark A
Arch Bronconeumol 2023 Mar;59(3):134-136. Epub 2022 Dec 18 doi: 10.1016/j.arbres.2022.12.001. PMID: 36639347
Ullmann N, Santamaria F, Allegorico A, Fainardi V, Borrelli M, Ferraro VA, Proietti E, Parisi GF, Romagnoli V, Lucca F, Gallucci M, Mappa L, Lelli M, Amato D, Petrarca L, Cimino G, Sacco O, Calogero C, Patria MF, Acquafredda A, Ferlisi A, Maschio M, Kantar A, Cutrera R
Pediatr Pulmonol 2023 Apr;58(4):1127-1135. Epub 2023 Jan 9 doi: 10.1002/ppul.26303. PMID: 36588099
Graziano S, Ullmann N, Rusciano R, Allegorico A, Boldrini F, Rosito L, Quittner AL, Cutrera R, Tabarini P
Respir Med 2023 Feb;207:107095. Epub 2022 Dec 23 doi: 10.1016/j.rmed.2022.107095. PMID: 36572068

Recent clinical studies

Etiology

Raidt J, Loges NT, Olbrich H, Wallmeier J, Pennekamp P, Omran H
Presse Med 2023 Sep;52(3):104171. Epub 2023 Jul 27 doi: 10.1016/j.lpm.2023.104171. PMID: 37516247
Newman L, Chopra J, Dossett C, Shepherd E, Bercusson A, Carroll M, Walker W, Lucas JS, Cheong Y
Hum Reprod Update 2023 May 2;29(3):347-367. doi: 10.1093/humupd/dmad003. PMID: 36721921Free 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
McConnachie DJ, Stow JL, Mallett AJ
Am J Kidney Dis 2021 Mar;77(3):410-419. Epub 2020 Oct 9 doi: 10.1053/j.ajkd.2020.08.012. PMID: 33039432
Guerri G, Maniscalchi T, Barati S, Dhuli K, Busetto GM, Del Giudice F, De Berardinis E, De Antoni L, Miertus J, Bertelli M
Acta Biomed 2019 Sep 30;90(10-S):75-82. doi: 10.23750/abm.v90i10-S.8764. PMID: 31577259Free PMC Article

Diagnosis

Raidt J, Loges NT, Olbrich H, Wallmeier J, Pennekamp P, Omran H
Presse Med 2023 Sep;52(3):104171. Epub 2023 Jul 27 doi: 10.1016/j.lpm.2023.104171. PMID: 37516247
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
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
Guerri G, Maniscalchi T, Barati S, Dhuli K, Busetto GM, Del Giudice F, De Berardinis E, De Antoni L, Miertus J, Bertelli M
Acta Biomed 2019 Sep 30;90(10-S):75-82. doi: 10.23750/abm.v90i10-S.8764. PMID: 31577259Free PMC Article

Therapy

Cardinale F, La Torre F, Tricarico LG, Verriello G, Mastrorilli C
Curr Pediatr Rev 2024;20(3):203-215. doi: 10.2174/1573396320666230912103056. PMID: 37702165
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
Bingol I, Gokdemir Y, Yilmaz-Yegit C, Ergenekon P, Atag E, Bas Ikizoglu N, Erdem Eralp E, Evkaya A, Gencer K, Saygi EK, Karakoc F, Ersu R, Karadag B
Pediatr Pulmonol 2020 Dec;55(12):3414-3420. Epub 2020 Oct 22 doi: 10.1002/ppul.25099. PMID: 32997437
Griese M, Scheuch G
Ann Am Thorac Soc 2016 Aug;13 Suppl 4:S346-51. doi: 10.1513/AnnalsATS.201507-469KV. PMID: 27564672
Knowles MR, Zariwala M, Leigh M
Clin Chest Med 2016 Sep;37(3):449-61. Epub 2016 Jun 30 doi: 10.1016/j.ccm.2016.04.008. PMID: 27514592Free PMC Article

Prognosis

Cardinale F, La Torre F, Tricarico LG, Verriello G, Mastrorilli C
Curr Pediatr Rev 2024;20(3):203-215. doi: 10.2174/1573396320666230912103056. PMID: 37702165
Pedersen ESL, Schreck LD, Goutaki M, Bellu S, Copeland F, Lucas JS, Zwahlen M, Kuehni CE
Int J Public Health 2023;68:1605561. Epub 2023 Aug 17 doi: 10.3389/ijph.2023.1605561. PMID: 37663372Free PMC Article
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
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
Simsek S, Inal-Ince D, Cakmak A, Emiralioglu N, Calik-Kutukcu E, Saglam M, Vardar-Yagli N, Ozcelik HU, Sonbahar-Ulu H, Bozdemir-Ozel C, Kiper N, Arikan H
Eur J Pediatr 2018 May;177(5):765-773. Epub 2018 Feb 27 doi: 10.1007/s00431-018-3121-2. PMID: 29487997

Clinical prediction guides

Newman L, Chopra J, Dossett C, Shepherd E, Bercusson A, Carroll M, Walker W, Lucas JS, Cheong Y
Hum Reprod Update 2023 May 2;29(3):347-367. doi: 10.1093/humupd/dmad003. PMID: 36721921Free PMC Article
Fırat M, Boşnak-Güçlü M, Şişmanlar-Eyüboğlu T, Aslan AT
Pediatr Pulmonol 2023 Jan;58(1):73-80. Epub 2022 Sep 28 doi: 10.1002/ppul.26158. PMID: 36114723
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
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

Cheng L, Dong Y, Liu S
J Cardiothorac Vasc Anesth 2023 Jun;37(6):1021-1025. Epub 2023 Feb 3 doi: 10.1053/j.jvca.2023.01.033. PMID: 36849313
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
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
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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