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Ciliary dyskinesia, primary, 49, without situs inversus(CILD49)

MedGen UID:
1824064
Concept ID:
C5774291
Disease or Syndrome
Synonym: CILD49
 
Gene (location): CFAP74 (1p36.33)
 
Monarch Initiative: MONDO:0859353
OMIM®: 620197

Definition

Primary ciliary dyskinesia-49 (CILD49) without situs inversus is an autosomal recessive disorder characterized by the onset of recurrent respiratory infections, chronic cough, and bronchiectasis in early childhood due to defective ciliary clearance. Affected males also show infertility due to defective flagellar morphology and function. Nasal nitric oxide (NO) levels are normal and situs abnormalities are not observed (Sha et al., 2020; Biebach et al., 2022). For a discussion of genetic heterogeneity of primary ciliary dyskinesia, see CILD1 (244400). [from OMIM]

Clinical features

From HPO
Male infertility
MedGen UID:
5796
Concept ID:
C0021364
Disease or Syndrome
The inability of the male to effect fertilization of an ovum after a specified period of unprotected intercourse. Male sterility is permanent infertility.
Short sperm flagella
MedGen UID:
1623693
Concept ID:
C4539787
Finding
Sperm cells with abnormally short flagella.
Coiled sperm flagella
MedGen UID:
1611216
Concept ID:
C4539789
Finding
Sperm cells whose flagella are twisted (coiled).
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 cough
MedGen UID:
507601
Concept ID:
C0010201
Sign or Symptom
A persistent cough, defined as a cough lasting longer than eight weeks in adults or longer than four weeks in children.
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.
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.

Professional guidelines

PubMed

Lucas JS, Barbato A, Collins SA, Goutaki M, Behan L, Caudri D, Dell S, Eber E, Escudier E, Hirst RA, Hogg C, Jorissen M, Latzin P, Legendre M, Leigh MW, Midulla F, Nielsen KG, Omran H, Papon JF, Pohunek P, Redfern B, Rigau D, Rindlisbacher B, Santamaria F, Shoemark A, Snijders D, Tonia T, Titieni A, Walker WT, Werner C, Bush A, Kuehni CE
Eur Respir J 2017 Jan;49(1) Epub 2017 Jan 4 doi: 10.1183/13993003.01090-2016. PMID: 27836958Free PMC Article
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
Busquets RM, Caballero-Rabasco MA, Velasco M, Lloreta J, García-Algar Ó
Arch Bronconeumol 2013 Mar;49(3):99-104. Epub 2012 Dec 23 doi: 10.1016/j.arbres.2012.10.007. PMID: 23265970

Recent clinical studies

Etiology

Chiyonobu K, Xu Y, Feng G, Saso S, Ogawa S, Ikejiri M, Abo M, Kondo M, Gotoh S, Kubo H, Hosoki K, Nagao M, Fujisawa T, Nakatani K, Takeuchi K
Auris Nasus Larynx 2022 Apr;49(2):248-257. Epub 2021 Aug 26 doi: 10.1016/j.anl.2021.08.003. PMID: 34454779
Olm MAK, Marson FAL, Athanazio RA, Nakagawa NK, Macchione M, Loges NT, Omran H, Rached SZ, Bertuzzo CS, Stelmach R, Saldiva PHN, Ribeiro JD, Jones MH, Mauad T
Sci Rep 2019 Jun 18;9(1):8693. doi: 10.1038/s41598-019-45017-1. PMID: 31213628Free PMC Article
Pifferi M, Bush A, Caramella D, Metelli MR, Di Cicco M, Piras M, Gherarducci G, Capristo C, Maggi F, Peroni D, Boner AL
Respir Med 2017 Mar;124:49-56. Epub 2017 Feb 2 doi: 10.1016/j.rmed.2017.02.001. PMID: 28284321
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
Hosie PH, Fitzgerald DA, Jaffe A, Birman CS, Rutland J, Morgan LC
J Paediatr Child Health 2015 Jul;51(7):722-6. Epub 2014 Dec 15 doi: 10.1111/jpc.12791. PMID: 25510893

Diagnosis

Chiyonobu K, Xu Y, Feng G, Saso S, Ogawa S, Ikejiri M, Abo M, Kondo M, Gotoh S, Kubo H, Hosoki K, Nagao M, Fujisawa T, Nakatani K, Takeuchi K
Auris Nasus Larynx 2022 Apr;49(2):248-257. Epub 2021 Aug 26 doi: 10.1016/j.anl.2021.08.003. PMID: 34454779
Suzaki I, Hirano K, Arai S, Maruyama Y, Mizuyoshi T, Tokudome T, Fujii N, Kobayashi H
Am J Case Rep 2020 Aug 30;21:e923270. doi: 10.12659/AJCR.923270. PMID: 32862191Free PMC Article
Olm MAK, Marson FAL, Athanazio RA, Nakagawa NK, Macchione M, Loges NT, Omran H, Rached SZ, Bertuzzo CS, Stelmach R, Saldiva PHN, Ribeiro JD, Jones MH, Mauad T
Sci Rep 2019 Jun 18;9(1):8693. doi: 10.1038/s41598-019-45017-1. PMID: 31213628Free PMC Article
Lucas JS, Barbato A, Collins SA, Goutaki M, Behan L, Caudri D, Dell S, Eber E, Escudier E, Hirst RA, Hogg C, Jorissen M, Latzin P, Legendre M, Leigh MW, Midulla F, Nielsen KG, Omran H, Papon JF, Pohunek P, Redfern B, Rigau D, Rindlisbacher B, Santamaria F, Shoemark A, Snijders D, Tonia T, Titieni A, Walker WT, Werner C, Bush A, Kuehni CE
Eur Respir J 2017 Jan;49(1) Epub 2017 Jan 4 doi: 10.1183/13993003.01090-2016. PMID: 27836958Free PMC Article
Boon M, Jorissen M, Proesmans M, De Boeck K
Eur J Pediatr 2013 Feb;172(2):151-62. Epub 2012 Jul 10 doi: 10.1007/s00431-012-1785-6. PMID: 22777640

Therapy

Paff T, Daniels JM, Weersink EJ, Lutter R, Vonk Noordegraaf A, Haarman EG
Eur Respir J 2017 Feb;49(2) Epub 2017 Feb 23 doi: 10.1183/13993003.01770-2016. PMID: 28232410
Lucas JS, Barbato A, Collins SA, Goutaki M, Behan L, Caudri D, Dell S, Eber E, Escudier E, Hirst RA, Hogg C, Jorissen M, Latzin P, Legendre M, Leigh MW, Midulla F, Nielsen KG, Omran H, Papon JF, Pohunek P, Redfern B, Rigau D, Rindlisbacher B, Santamaria F, Shoemark A, Snijders D, Tonia T, Titieni A, Walker WT, Werner C, Bush A, Kuehni CE
Eur Respir J 2017 Jan;49(1) Epub 2017 Jan 4 doi: 10.1183/13993003.01090-2016. PMID: 27836958Free PMC Article
Gokdemir Y, Karadag-Saygi E, Erdem E, Bayindir O, Ersu R, Karadag B, Sekban N, Akyuz G, Karakoc F
Pediatr Pulmonol 2014 Jun;49(6):611-6. Epub 2013 Aug 30 doi: 10.1002/ppul.22861. PMID: 24039238
Boon M, Jorissen M, Proesmans M, De Boeck K
Eur J Pediatr 2013 Feb;172(2):151-62. Epub 2012 Jul 10 doi: 10.1007/s00431-012-1785-6. PMID: 22777640
Swisher M, Jonas R, Tian X, Lee ES, Lo CW, Leatherbury L
J Thorac Cardiovasc Surg 2011 Mar;141(3):637-44, 644.e1-3. Epub 2010 Sep 29 doi: 10.1016/j.jtcvs.2010.07.082. PMID: 20884020Free PMC Article

Prognosis

Suzaki I, Hirano K, Arai S, Maruyama Y, Mizuyoshi T, Tokudome T, Fujii N, Kobayashi H
Am J Case Rep 2020 Aug 30;21:e923270. doi: 10.12659/AJCR.923270. PMID: 32862191Free PMC Article
Nyilas S, Schlegtendal A, Singer F, Goutaki M, Kuehni CE, Casaulta C, Latzin P, Koerner-Rettberg C
Eur Respir J 2017 Jan;49(1) Epub 2017 Jan 25 doi: 10.1183/13993003.00466-2016. PMID: 28122863
Goutaki M, Maurer E, Halbeisen FS, Amirav I, Barbato A, Behan L, Boon M, Casaulta C, Clement A, Crowley S, Haarman E, Hogg C, Karadag B, Koerner-Rettberg C, Leigh MW, Loebinger MR, Mazurek H, Morgan L, Nielsen KG, Omran H, Schwerk N, Scigliano S, Werner C, Yiallouros P, Zivkovic Z, Lucas JS, Kuehni CE; PCD Italian Consortium; Swiss PCD Group; French Reference Centre for Rare Lung Diseases; Genetic Disorders of Mucociliary Clearance Consortium
Eur Respir J 2017 Jan;49(1) Epub 2017 Jan 4 doi: 10.1183/13993003.01181-2016. PMID: 28052956Free PMC Article
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
Green K, Buchvald FF, Marthin JK, Hanel B, Gustafsson PM, Nielsen KG
Thorax 2012 Jan;67(1):49-53. Epub 2011 Sep 26 doi: 10.1136/thoraxjnl-2011-200726. PMID: 21953064

Clinical prediction guides

Chiyonobu K, Xu Y, Feng G, Saso S, Ogawa S, Ikejiri M, Abo M, Kondo M, Gotoh S, Kubo H, Hosoki K, Nagao M, Fujisawa T, Nakatani K, Takeuchi K
Auris Nasus Larynx 2022 Apr;49(2):248-257. Epub 2021 Aug 26 doi: 10.1016/j.anl.2021.08.003. PMID: 34454779
Olm MAK, Marson FAL, Athanazio RA, Nakagawa NK, Macchione M, Loges NT, Omran H, Rached SZ, Bertuzzo CS, Stelmach R, Saldiva PHN, Ribeiro JD, Jones MH, Mauad T
Sci Rep 2019 Jun 18;9(1):8693. doi: 10.1038/s41598-019-45017-1. PMID: 31213628Free PMC Article
Pifferi M, Bush A, Caramella D, Metelli MR, Di Cicco M, Piras M, Gherarducci G, Capristo C, Maggi F, Peroni D, Boner AL
Respir Med 2017 Mar;124:49-56. Epub 2017 Feb 2 doi: 10.1016/j.rmed.2017.02.001. PMID: 28284321
Goutaki M, Maurer E, Halbeisen FS, Amirav I, Barbato A, Behan L, Boon M, Casaulta C, Clement A, Crowley S, Haarman E, Hogg C, Karadag B, Koerner-Rettberg C, Leigh MW, Loebinger MR, Mazurek H, Morgan L, Nielsen KG, Omran H, Schwerk N, Scigliano S, Werner C, Yiallouros P, Zivkovic Z, Lucas JS, Kuehni CE; PCD Italian Consortium; Swiss PCD Group; French Reference Centre for Rare Lung Diseases; Genetic Disorders of Mucociliary Clearance Consortium
Eur Respir J 2017 Jan;49(1) Epub 2017 Jan 4 doi: 10.1183/13993003.01181-2016. PMID: 28052956Free PMC Article
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

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