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Ciliary dyskinesia, primary, 46(CILD46)

MedGen UID:
1780196
Concept ID:
C5543646
Disease or Syndrome
Synonyms: CILD46; CILIARY DYSKINESIA, PRIMARY, 46
 
Gene (location): STK36 (2q35)
 
Monarch Initiative: MONDO:0030332
OMIM®: 619436

Definition

Primary ciliary dyskinesia-46 (CILD46) is characterized by recurrent sinus and respiratory infections, with reduced pulmonary function and uncoordinated beating of respiratory cilia. No situs abnormalities have been observed (Edelbusch et al., 2017). For a general phenotypic description and a discussion of genetic heterogeneity of primary ciliary dyskinesia, see CILD1 (244400). [from OMIM]

Clinical features

From HPO
Reduced sperm motility
MedGen UID:
907698
Concept ID:
C4082176
Finding
An abnormal reduction in the mobility of ejaculated sperm.
Hearing impairment
MedGen UID:
235586
Concept ID:
C1384666
Disease or Syndrome
A decreased magnitude of the sensory perception of sound.
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 pneumonia
MedGen UID:
195802
Concept ID:
C0694550
Disease or Syndrome
An increased susceptibility to pneumonia as manifested by a history of recurrent episodes of pneumonia.
Reduced forced vital capacity
MedGen UID:
337630
Concept ID:
C1846678
Finding
An abnormal reduction in the amount of air a person can expel following maximal inspiration.
Reduced forced expiratory volume in one second
MedGen UID:
1687063
Concept ID:
C5139283
Finding
An abnormal reduction in the amount of air a person can forcefully expel in one second.
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.

Professional guidelines

PubMed

Raidt J, Riepenhausen S, Pennekamp P, Olbrich H, Amirav I, Athanazio RA, Aviram M, Balinotti JE, Bar-On O, Bode SFN, Boon M, Borrelli M, Carr SB, Crowley S, Dehlink E, Diepenhorst S, Durdik P, Dworniczak B, Emiralioğlu N, Erdem E, Fonnesu R, Gracci S, Große-Onnebrink J, Gwozdziewicz K, Haarman EG, Hansen CR, Hogg C, Holgersen MG, Kerem E, Körner RW, Kötz K, Kouis P, Loebinger MR, Lorent N, Lucas JS, Maj D, Mall MA, Marthin JK, Martinu V, Mazurek H, Mitchison HM, Nöthe-Menchen T, Özçelik U, Pifferi M, Pogorzelski A, Ringshausen FC, Roehmel JF, Rovira-Amigo S, Rumman N, Schlegtendal A, Shoemark A, Sperstad Kennelly S, Staar BO, Sutharsan S, Thomas S, Ullmann N, Varghese J, von Hardenberg S, Walker WT, Wetzke M, Witt M, Yiallouros P, Zschocke A, Ziętkiewicz E, Nielsen KG, Omran H
Eur Respir J 2024 Aug;64(2) Epub 2024 Aug 8 doi: 10.1183/13993003.01769-2023. PMID: 38871375Free PMC Article
Çağlar HT, Pekcan S, Erden S, Ünal G, Yılmaz Aİ, Ercan F, Savaş S, Ayman FN, İstanbullu HA
Pediatr Pulmonol 2024 Oct;59(10):2457-2463. Epub 2024 May 2 doi: 10.1002/ppul.27038. PMID: 38695576
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

Recent clinical studies

Etiology

Çağlar HT, Pekcan S, Erden S, Ünal G, Yılmaz Aİ, Ercan F, Savaş S, Ayman FN, İstanbullu HA
Pediatr Pulmonol 2024 Oct;59(10):2457-2463. Epub 2024 May 2 doi: 10.1002/ppul.27038. PMID: 38695576
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
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
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
Bhatt JM, Muhonen EG, Meier M, Sagel SD, Chan KH
Otolaryngol Head Neck Surg 2019 Nov;161(5):877-880. Epub 2019 Sep 10 doi: 10.1177/0194599819874842. PMID: 31500503

Diagnosis

Pieters ALP, van der Veer T, Meerburg JJ, Andrinopoulou ER, van der Eerden MM, Ciet P, Aliberti S, Burgel PR, Crichton ML, Shoemark A, Goeminne PC, Shteinberg M, Loebinger MR, Haworth CS, Blasi F, Tiddens HAWM, Caudri D, Chalmers JD
Am J Respir Crit Care Med 2024 Jul 1;210(1):87-96. doi: 10.1164/rccm.202311-2109OC. PMID: 38635862
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
Bhatt JM, Muhonen EG, Meier M, Sagel SD, Chan KH
Otolaryngol Head Neck Surg 2019 Nov;161(5):877-880. Epub 2019 Sep 10 doi: 10.1177/0194599819874842. PMID: 31500503
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
Mullowney T, Manson D, Kim R, Stephens D, Shah V, Dell S
Pediatrics 2014 Dec;134(6):1160-6. doi: 10.1542/peds.2014-0808. PMID: 25422025Free PMC Article

Therapy

Haworth CS, Shteinberg M, Winthrop K, Barker A, Blasi F, Dimakou K, Morgan LC, O'Donnell AE, Ringshausen FC, Sibila O, Thomson RM, Carroll KJ, Pontenani F, Castellani P, Chalmers JD; PROMIS trial investigators
Lancet Respir Med 2024 Oct;12(10):787-798. Epub 2024 Sep 10 doi: 10.1016/S2213-2600(24)00225-X. PMID: 39270696
Abelson D, Di Michiel J, Frater C, Pearson M, Russo R, Wechselberger M, Cottee A, Morgan L
Thorax 2024 Jun 14;79(7):607-614. doi: 10.1136/thorax-2023-221052. PMID: 38378235
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
Schlösser TPC, Semple T, Carr SB, Padley S, Loebinger MR, Hogg C, Castelein RM
Eur Spine J 2017 Jun;26(6):1595-1599. Epub 2017 Feb 8 doi: 10.1007/s00586-017-4970-5. PMID: 28180983
Mullowney T, Manson D, Kim R, Stephens D, Shah V, Dell S
Pediatrics 2014 Dec;134(6):1160-6. doi: 10.1542/peds.2014-0808. PMID: 25422025Free PMC Article

Prognosis

Çağlar HT, Pekcan S, Erden S, Ünal G, Yılmaz Aİ, Ercan F, Savaş S, Ayman FN, İstanbullu HA
Pediatr Pulmonol 2024 Oct;59(10):2457-2463. Epub 2024 May 2 doi: 10.1002/ppul.27038. PMID: 38695576
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
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
Bhatt JM, Muhonen EG, Meier M, Sagel SD, Chan KH
Otolaryngol Head Neck Surg 2019 Nov;161(5):877-880. Epub 2019 Sep 10 doi: 10.1177/0194599819874842. PMID: 31500503
Mullowney T, Manson D, Kim R, Stephens D, Shah V, Dell S
Pediatrics 2014 Dec;134(6):1160-6. doi: 10.1542/peds.2014-0808. PMID: 25422025Free PMC Article

Clinical prediction guides

Raidt J, Riepenhausen S, Pennekamp P, Olbrich H, Amirav I, Athanazio RA, Aviram M, Balinotti JE, Bar-On O, Bode SFN, Boon M, Borrelli M, Carr SB, Crowley S, Dehlink E, Diepenhorst S, Durdik P, Dworniczak B, Emiralioğlu N, Erdem E, Fonnesu R, Gracci S, Große-Onnebrink J, Gwozdziewicz K, Haarman EG, Hansen CR, Hogg C, Holgersen MG, Kerem E, Körner RW, Kötz K, Kouis P, Loebinger MR, Lorent N, Lucas JS, Maj D, Mall MA, Marthin JK, Martinu V, Mazurek H, Mitchison HM, Nöthe-Menchen T, Özçelik U, Pifferi M, Pogorzelski A, Ringshausen FC, Roehmel JF, Rovira-Amigo S, Rumman N, Schlegtendal A, Shoemark A, Sperstad Kennelly S, Staar BO, Sutharsan S, Thomas S, Ullmann N, Varghese J, von Hardenberg S, Walker WT, Wetzke M, Witt M, Yiallouros P, Zschocke A, Ziętkiewicz E, Nielsen KG, Omran H
Eur Respir J 2024 Aug;64(2) Epub 2024 Aug 8 doi: 10.1183/13993003.01769-2023. PMID: 38871375Free PMC Article
Çağlar HT, Pekcan S, Erden S, Ünal G, Yılmaz Aİ, Ercan F, Savaş S, Ayman FN, İstanbullu HA
Pediatr Pulmonol 2024 Oct;59(10):2457-2463. Epub 2024 May 2 doi: 10.1002/ppul.27038. PMID: 38695576
Pieters ALP, van der Veer T, Meerburg JJ, Andrinopoulou ER, van der Eerden MM, Ciet P, Aliberti S, Burgel PR, Crichton ML, Shoemark A, Goeminne PC, Shteinberg M, Loebinger MR, Haworth CS, Blasi F, Tiddens HAWM, Caudri D, Chalmers JD
Am J Respir Crit Care Med 2024 Jul 1;210(1):87-96. doi: 10.1164/rccm.202311-2109OC. PMID: 38635862
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
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

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
Møller ME, Alanin MC, Grønhøj C, Aanæs K, Høiby N, von Buchwald C
Am J Rhinol Allergy 2017 Sep 1;31(5):293-298. doi: 10.2500/ajra.2017.31.4461. PMID: 28859703Free PMC Article

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