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Primary ciliary dyskinesia 22(CILD22)

MedGen UID:
815873
Concept ID:
C3809543
Disease or Syndrome
Synonym: CILIARY DYSKINESIA, PRIMARY, 22, WITH OR WITHOUT SITUS INVERSUS
 
Gene (location): ZMYND10 (3p21.31)
 
Monarch Initiative: MONDO:0014192
OMIM®: 615444

Definition

Primary ciliary dyskinesia-22 (CILD22) is an autosomal recessive disorder caused by defective structure and function of cilia or flagella. Ciliary dysfunction causes respiratory distress in term neonates, impaired mucociliary clearance, chronic cough, sinusitis, bronchiectasis, and male infertility. Defective motility of embryonic nodal cilia leads to situs abnormalities in about 50% of patients. CILD22 is characterized by defects of the inner and outer dynein arms (summary by Zariwala et al., 2013). For a 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.
Reduced sperm motility
MedGen UID:
907698
Concept ID:
C4082176
Finding
An abnormal reduction in the mobility of ejaculated sperm.
Dextrocardia
MedGen UID:
4255
Concept ID:
C0011813
Congenital Abnormality
The heart is located in the right hand sided hemithorax. That is, there is a left-right reversal (or "mirror reflection") of the anatomical location of the heart in which the heart is locate on the right side instead of the left.
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.
Chronic bronchitis
MedGen UID:
3084
Concept ID:
C0008677
Disease or Syndrome
Chronic inflammation of the bronchi.
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.
Immotile cilia
MedGen UID:
383738
Concept ID:
C1855672
Finding
Respiratory insufficiency due to defective ciliary clearance
MedGen UID:
765013
Concept ID:
C3552099
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 inner and outer dynein arms
MedGen UID:
868587
Concept ID:
C4022986
Finding
Complete absence of the dynein arms of respiratory motile cilia, that is, absence of the inner and the outer dynein arms, which normally are situated inside and outside of the peripheral microtubules of motile cilia. This feature is usually appreciated by electron microscopy.
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.
Nasal polyposis
MedGen UID:
6524
Concept ID:
C0027430
Anatomical Abnormality
Polypoidal masses arising mainly from the mucous membranes of the nose and paranasal sinuses. They are freely movable and nontender overgrowths of the mucosa that frequently accompany allergic rhinitis.
Rhinitis
MedGen UID:
19782
Concept ID:
C0035455
Disease or Syndrome
Inflammation of the nasal mucosa with nasal congestion.

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
Brennan SK, Ferkol TW, Davis SD
Int J Mol Sci 2021 Jul 31;22(15) doi: 10.3390/ijms22158272. PMID: 34361034Free PMC Article
Dąbkowska S, Kucińska-Chahwan A, Beneturska A, Ilnicka A, Nowakowska B, Panek G, Roszkowski T, Bijok J
Prenat Diagn 2020 Apr;40(5):612-617. Epub 2020 Feb 12 doi: 10.1002/pd.5654. PMID: 32003477

Recent clinical studies

Etiology

Piatti G, Ambrosetti U, Aldè M, Girotto G, Concas MP, Torretta S
Laryngoscope 2023 Feb;133(2):248-254. Epub 2022 Mar 21 doi: 10.1002/lary.30112. PMID: 35312075Free PMC Article
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
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
Keniş Coşkun Ö, Gençer Atalay K, Erdem E, Karadag-Saygi E, Gökdemir Y, Karadağ B
Pediatr Pulmonol 2019 Dec;54(12):1936-1940. Epub 2019 Aug 29 doi: 10.1002/ppul.24503. PMID: 31468736
Fuger M, Aupiais C, Thouvenin G, Taytard J, Tamalet A, Escudier E, Boizeau P, Corvol H, Beydon N
Respir Physiol Neurobiol 2018 May;251:1-7. Epub 2018 Jan 31 doi: 10.1016/j.resp.2018.01.010. PMID: 29366817

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
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
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
van der Vaart J, Böttinger L, Geurts MH, van de Wetering WJ, Knoops K, Sachs N, Begthel H, Korving J, Lopez-Iglesias C, Peters PJ, Eitan K, Gileles-Hillel A, Clevers H
EMBO Rep 2021 Dec 6;22(12):e52058. Epub 2021 Oct 25 doi: 10.15252/embr.202052058. PMID: 34693619Free PMC Article
Werner C, Lablans M, Ataian M, Raidt J, Wallmeier J, Große-Onnebrink J, Kuehni CE, Haarman EG, Leigh MW, Quittner AL, Lucas JS, Hogg C, Witt M, Priftis KN, Yiallouros P, Nielsen KG, Santamaria F, Ückert F, Omran H
Eur Respir J 2016 Mar;47(3):849-59. Epub 2015 Dec 8 doi: 10.1183/13993003.00776-2015. PMID: 26659107

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
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
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
Paff T, Omran H, Nielsen KG, Haarman EG
Int J Mol Sci 2021 Sep 11;22(18) doi: 10.3390/ijms22189834. PMID: 34575997Free PMC Article
Hornef N, Olbrich H, Horvath J, Zariwala MA, Fliegauf M, Loges NT, Wildhaber J, Noone PG, Kennedy M, Antonarakis SE, Blouin JL, Bartoloni L, Nüsslein T, Ahrens P, Griese M, Kuhl H, Sudbrak R, Knowles MR, Reinhardt R, Omran H
Am J Respir Crit Care Med 2006 Jul 15;174(2):120-6. Epub 2006 Apr 20 doi: 10.1164/rccm.200601-084OC. PMID: 16627867Free 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
Paternò S, Pisani L, Zanconato S, Ferraro VA, Carraro S
Int J Mol Sci 2023 Nov 10;24(22) doi: 10.3390/ijms242216159. PMID: 38003348Free 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
Werner C, Lablans M, Ataian M, Raidt J, Wallmeier J, Große-Onnebrink J, Kuehni CE, Haarman EG, Leigh MW, Quittner AL, Lucas JS, Hogg C, Witt M, Priftis KN, Yiallouros P, Nielsen KG, Santamaria F, Ückert F, Omran H
Eur Respir J 2016 Mar;47(3):849-59. Epub 2015 Dec 8 doi: 10.1183/13993003.00776-2015. PMID: 26659107
Mirra V, Caffarelli C, Maglione M, Valentino R, Perruolo G, Mazzarella C, Di Micco LL, Montella S, Santamaria F
Ital J Pediatr 2015 Feb 22;41:14. doi: 10.1186/s13052-015-0119-5. PMID: 25887861Free 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
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
van der Vaart J, Böttinger L, Geurts MH, van de Wetering WJ, Knoops K, Sachs N, Begthel H, Korving J, Lopez-Iglesias C, Peters PJ, Eitan K, Gileles-Hillel A, Clevers H
EMBO Rep 2021 Dec 6;22(12):e52058. Epub 2021 Oct 25 doi: 10.15252/embr.202052058. PMID: 34693619Free PMC Article
Werner C, Lablans M, Ataian M, Raidt J, Wallmeier J, Große-Onnebrink J, Kuehni CE, Haarman EG, Leigh MW, Quittner AL, Lucas JS, Hogg C, Witt M, Priftis KN, Yiallouros P, Nielsen KG, Santamaria F, Ückert F, Omran H
Eur Respir J 2016 Mar;47(3):849-59. Epub 2015 Dec 8 doi: 10.1183/13993003.00776-2015. PMID: 26659107
Hornef N, Olbrich H, Horvath J, Zariwala MA, Fliegauf M, Loges NT, Wildhaber J, Noone PG, Kennedy M, Antonarakis SE, Blouin JL, Bartoloni L, Nüsslein T, Ahrens P, Griese M, Kuhl H, Sudbrak R, Knowles MR, Reinhardt R, Omran H
Am J Respir Crit Care Med 2006 Jul 15;174(2):120-6. Epub 2006 Apr 20 doi: 10.1164/rccm.200601-084OC. PMID: 16627867Free PMC Article

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
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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