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Ciliary dyskinesia, primary, 43(CILD43)

MedGen UID:
1684675
Concept ID:
C5231466
Disease or Syndrome
Synonym: CILIARY DYSKINESIA, PRIMARY, 43, WITH OR WITHOUT SITUS INVERSUS
 
Gene (location): FOXJ1 (17q25.1)
 
Monarch Initiative: MONDO:0032874
OMIM®: 618699

Definition

Primary ciliary dyskinesia-43 (CILD43) is a disorder characterized by a defect in motile cilia and ciliary clearance resulting in the onset of respiratory insufficiency soon after birth, and associated with recurrent upper and lower respiratory infections with chronic progressive lung disease. Patients with this disorder also develop significant obstructive hydrocephalus requiring shunting in infancy, although adult onset of neurologic symptoms may occur. Other more variable features include infertility and about a 50% chance of situs inversus or other left-right asymmetry defects. The disorder is considered to be a type of ciliopathy known as 'reduced generation of multiple motile cilia' (RGMC) (summary by Wallmeier et al., 2019). For a discussion of genetic heterogeneity of primary ciliary dyskinesia, CILD1 (244400). [from OMIM]

Clinical features

From HPO
Abdominal situs inversus
MedGen UID:
52359
Concept ID:
C0037221
Congenital Abnormality
A left-right reversal (or mirror reflection) of the anatomical location of the viscera of the abdomen.
Noncommunicating hydrocephalus
MedGen UID:
108198
Concept ID:
C0549423
Disease or Syndrome
A form of hydrocephalus in which the flow of cerebrospinal fluid (CSF) within the cerebral ventricular system or in the outlets of the CSF to the arachnoid space is obstructed.
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.
Productive cough
MedGen UID:
66781
Concept ID:
C0239134
Finding
A cough that produces phlegm or mucus.
Recurrent upper respiratory tract infections
MedGen UID:
154380
Concept ID:
C0581381
Disease or Syndrome
An increased susceptibility to upper respiratory tract infections as manifested by a history of recurrent upper respiratory tract infections (running ears - otitis, sinusitis, pharyngitis, tonsillitis).
Recurrent lower respiratory tract infections
MedGen UID:
756211
Concept ID:
C3163798
Disease or Syndrome
An increased susceptibility to lower respiratory tract infections as manifested by a history of recurrent lower respiratory tract infections.
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.
Chronic rhinitis
MedGen UID:
3086
Concept ID:
C0008711
Disease or Syndrome
Chronic inflammation of the nasal mucosa.

Professional guidelines

PubMed

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
Dell SD, Leigh MW, Lucas JS, Ferkol TW, Knowles MR, Alpern A, Behan L, Morris AM, Hogg C, DunnGalvin A, Quittner AL
Ann Am Thorac Soc 2016 Oct;13(10):1726-1735. doi: 10.1513/AnnalsATS.201603-198OC. PMID: 27464304Free PMC Article
Noone PG, Leigh MW, Sannuti A, Minnix SL, Carson JL, Hazucha M, Zariwala MA, Knowles MR
Am J Respir Crit Care Med 2004 Feb 15;169(4):459-67. Epub 2003 Dec 4 doi: 10.1164/rccm.200303-365OC. PMID: 14656747

Recent clinical studies

Etiology

Marro M, Leiva-Juárez MM, D'Ovidio F, Chan J, Van Raemdonck D, Ceulemans LJ, Moreno P, Kindelan AA, Krueger T, Koutsokera A, Ehrsam JP, Inci I, Yazicioglu A, Yekeler E, Boffini M, Brioude G, Thomas PA, Pizanis N, Aigner C, Schiavon M, Rea F, Anile M, Venuta F, Keshavjee S
Transpl Int 2023;36:10819. Epub 2023 Feb 14 doi: 10.3389/ti.2023.10819. PMID: 36865666Free PMC Article
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
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
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
Dell SD, Leigh MW, Lucas JS, Ferkol TW, Knowles MR, Alpern A, Behan L, Morris AM, Hogg C, DunnGalvin A, Quittner AL
Ann Am Thorac Soc 2016 Oct;13(10):1726-1735. doi: 10.1513/AnnalsATS.201603-198OC. PMID: 27464304Free PMC Article

Diagnosis

Goutaki M, Shoemark A
Clin Chest Med 2022 Mar;43(1):127-140. doi: 10.1016/j.ccm.2021.11.008. PMID: 35236553
Baz-Redón N, Rovira-Amigo S, Paramonov I, Castillo-Corullón S, Cols Roig M, Antolín M, García Arumí E, Torrent-Vernetta A, de Mir Messa I, Gartner S, Iglesias Serrano I, Caballero-Rabasco MA, Asensio de la Cruz Ó, Vizmanos-Lamotte G, Martín de Vicente C, Martínez-Colls MDM, Reula A, Escribano A, Dasí F, Armengot-Carceller M, Polverino E, Amengual Pieras E, Amaro-Rodríguez R, Garrido-Pontnou M, Tizzano E, Camats-Tarruella N, Fernández-Cancio M, Moreno-Galdó A
Arch Bronconeumol (Engl Ed) 2021 Mar;57(3):186-194. Epub 2020 Apr 3 doi: 10.1016/j.arbres.2020.02.010. PMID: 32253119
Takeuchi K, Kitano M, Ishinaga H, Kobayashi M, Ogawa S, Nakatani K, Masuda S, Nagao M, Fujisawa T
Auris Nasus Larynx 2016 Jun;43(3):229-36. Epub 2015 Oct 31 doi: 10.1016/j.anl.2015.09.012. PMID: 26527516
Fauroux B, Bush A
Paediatr Respir Rev 2009 Jun;10(2):43. Epub 2009 Apr 16 doi: 10.1016/j.prrv.2008.11.002. PMID: 19410199
Santamaria F, De Stefano S, Montella S, Barbarano F, Iacotucci P, Ciccarelli R, Sofia M, Maniscalco M
Med Sci Monit 2008 Feb;14(2):CR80-85. PMID: 18227765

Therapy

Qian L, Lam B, Zheng T, Russo D, Ma J, Yao X
P R Health Sci J 2024 Sep;43(3):119-124. PMID: 39269762
Shkeiri R, Saliba W, Stein N, Najjar R, Weber G, Dror SK, Mishan PS, Adir Y, Shteinberg M
Respir Med 2021 Aug-Sep;185:106487. Epub 2021 Jun 8 doi: 10.1016/j.rmed.2021.106487. PMID: 34139580
Crowley S, Holgersen MG, Nielsen KG
Chron Respir Dis 2019 Jan-Dec;16:1479972318787919. Epub 2018 Jul 18 doi: 10.1177/1479972318787919. PMID: 30021461Free PMC Article
Zahid M, Bais A, Tian X, Devine W, Lee DM, Yau C, Sonnenberg D, Beerman L, Khalifa O, Lo CW
PLoS One 2018;13(2):e0191605. Epub 2018 Feb 14 doi: 10.1371/journal.pone.0191605. PMID: 29444099Free PMC Article
Noone PG, Bennett WD, Regnis JA, Zeman KL, Carson JL, King M, Boucher RC, Knowles MR
Am J Respir Crit Care Med 1999 Jul;160(1):144-9. doi: 10.1164/ajrccm.160.1.9806146. PMID: 10390392

Prognosis

Günaydın RÖ, Eroğlu E, Tellioğlu B, Emiralioğlu N, Özçelik HU, Yalçın E, Doğru D, Kiper EN
Int J Pediatr Otorhinolaryngol 2023 May;168:111520. Epub 2023 Mar 22 doi: 10.1016/j.ijporl.2023.111520. PMID: 36990030
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
Goutaki M, Shoemark A
Clin Chest Med 2022 Mar;43(1):127-140. doi: 10.1016/j.ccm.2021.11.008. PMID: 35236553
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
Dell SD, Leigh MW, Lucas JS, Ferkol TW, Knowles MR, Alpern A, Behan L, Morris AM, Hogg C, DunnGalvin A, Quittner AL
Ann Am Thorac Soc 2016 Oct;13(10):1726-1735. doi: 10.1513/AnnalsATS.201603-198OC. PMID: 27464304Free PMC Article

Clinical prediction guides

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
Goutaki M, Shoemark A
Clin Chest Med 2022 Mar;43(1):127-140. doi: 10.1016/j.ccm.2021.11.008. PMID: 35236553
Asfuroglu P, Ramasli Gursoy T, Sismanlar Eyuboglu T, Aslan AT
Pediatr Pulmonol 2021 Aug;56(8):2717-2723. Epub 2021 Jun 21 doi: 10.1002/ppul.25533. PMID: 34133086
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
Dell SD, Leigh MW, Lucas JS, Ferkol TW, Knowles MR, Alpern A, Behan L, Morris AM, Hogg C, DunnGalvin A, Quittner AL
Ann Am Thorac Soc 2016 Oct;13(10):1726-1735. doi: 10.1513/AnnalsATS.201603-198OC. PMID: 27464304Free PMC Article

Recent systematic reviews

Qian L, Lam B, Zheng T, Russo D, Ma J, Yao X
P R Health Sci J 2024 Sep;43(3):119-124. PMID: 39269762

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