266
Views
8
CrossRef citations to date
0
Altmetric
Review

Clinical phenotype and current diagnostic criteria for primary ciliary dyskinesia

, , &
Pages 1163-1175 | Received 02 Apr 2016, Accepted 26 Sep 2016, Published online: 19 Oct 2016

References

  • Afzelius BA. A human syndrome caused by immotile cilia. Science. 1976;193:317–319.
  • Kartagener M. Zur pathogenese der bronchiektasien. I. Mitteilung: bronchiekatsien bei situs viscerum inversus. Beitr Klin Tuberk. 1933;83:489–501.
  • Fliegauf M, Olbrich H, Horvath J, et al. Mislocalization of DNAH5 and DNAH9 in respiratory cells from patients with primary ciliary dyskinesia. Am J Respir Crit Care Med. 2005;171:1343–1349.
  • Chilvers MA, O’Callaghan C. Analysis of ciliary beat pattern and beat frequency using digital high speed imaging: comparison with the photomultiplier and photodiode methods. Thorax. 2000;55:314–317.
  • Jackson CL, Goggin PM, Lucas JS. Ciliary beat pattern analysis below 37 degrees C may increase risk of primary ciliary dyskinesia misdiagnosis. Chest. 2012;142:543–544.
  • Shah AS, Ben-Shahar Y, Moninger TO, et al. Motile cilia of human airway epithelia are chemosensory. Science. 2009;325:1131–1134.
  • Lee RJ, Xiong G, Kofonow JM, et al. T2R38 taste receptor polymorphisms underlie susceptibility to upper respiratory infection. J Clin Invest. 2012;122:4145–4159.
  • Munro NC, Currie DC, Lindsay KS, et al. Fertility in men with primary ciliary dyskinesia presenting with respiratory infection. Thorax. 1994;49:684–687.
  • Onoufriadis A, Paff T, Antony D, et al. Splice-site mutations in the axonemal outer dynein arm docking complex gene CCDC114 cause primary ciliary dyskinesia. Am J Hum Genet. 2013;92:88–98.
  • Olbrich H, Schmidts M, Werner C, et al. Recessive HYDIN mutations cause primary ciliary dyskinesia without randomization of left-right body asymmetry. Am J Hum Genet. 2012;91:672–684.
  • Pedersen LB, Veland IR, Schroder JM, et al. Assembly of primary cilia. Dev Dyn. 2008;237:1993–2006.
  • Colantonio JR, Vermot J, Wu D, et al. The dynein regulatory complex is required for ciliary motility and otolith biogenesis in the inner ear. Nature. 2009;457:205–209.
  • Falk N, Losl M, Schroder N, et al. Specialized Cilia in mammalian sensory systems. Cells. 2015;4:500–519.
  • Retailleau K, Duprat F. Polycystins and partners: proposed role in mechanosensitivity. J Physiol. 2014;592:2453–2471.
  • Valente EM, Rosti RO, Gibbs E, et al. Primary cilia in neurodevelopmental disorders. Nat Rev Neurol. 2014;10:27–36.
  • van Reeuwijk J, Arts HH, Roepman R. Scrutinizing ciliopathies by unraveling ciliary interaction networks. Hum Mol Genet. 2011;20:R149–57.
  • Rosenbaum JL, Witman GB. Intraflagellar transport. Nat Rev Mol Cell Biol. 2002;3:813–825.
  • Sung CH, Leroux MR. The roles of evolutionarily conserved functional modules in cilia-related trafficking. Nat Cell Biol. 2013;15:1387–1397.
  • Armengot M, Salom D, Diaz-Llopis M, et al. Nasal ciliary beat frequency and beat pattern in retinal ciliopathies. Invest Ophthalmol Vis Sci. 2012;53:2076–2079.
  • Li Y, Garrod AS, Madan-Khetarpal S, et al. Respiratory motile cilia dysfunction in a patient with cranioectodermal dysplasia. Am J Med Genet A. 2015;167A:2188–2196.
  • Knowles M, Zariwala M. Primary ciliary dyskinesia. Orphanet encyclopedia, May 2014. Available from: http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=GB&Expert=244.
  • Afzelius BA, Stenram U. Prevalence and genetics of immotile-cilia syndrome and left-handedness. Int J Dev Biol. 2006;50:571–573.
  • Torgersen J. Transposition of viscera, bronchiectasis and nasal polyps; a genetical analysis and a contribution to the problem of constitution. Acta Radiol. 1947;28:17–24.
  • Kuehni CE, Frischer T, Strippoli MP, et al. Factors influencing age at diagnosis of primary ciliary dyskinesia in European children. Eur Respir J. 2010;36:1248–1258.
  • Werner C, Lablans M, Ataian M, et al. An international registry for primary ciliary dyskinesia. Eur Respir J. 2016;47:849–859.
  • Leigh MW, Ferkol TW, Davis SD, et al. Clinical features and associated likelihood of primary ciliary dyskinesia in children and adolescents. Ann Am Thorac Soc. 2016;13:1305–1313; [ Epub ahead of print].
  • Ellerman A, Bisgaard H. Longitudinal study of lung function in a cohort of primary ciliary dyskinesia. Eur Respir J. 1997;10:2376–2379.
  • Shah A, Shoemark A, MacNeill SJ, et al. A longitudinal study characterising a large adult primary ciliary dyskinesia population. Eur Respir J. 2016;48:441–450; [Epub ahead of print].
  • Alanin MC, Nielsen KG, Von Buchwald C, et al. A longitudinal study of lung bacterial pathogens in patients with primary ciliary dyskinesia. Clin Microbiol Infect. 2015;21(1093):e1–7.
  • Maglione M, Bush A, Nielsen KG, et al. Multicenter analysis of body mass index, lung function, and sputum microbiology in primary ciliary dyskinesia. Pediatr Pulmonol. 2014;49:1243–1250.
  • Kennedy MP, Omran H, Leigh MW, et al. Congenital heart disease and other heterotaxic defects in a large cohort of patients with primary ciliary dyskinesia. Circulation. 2007;115:2814–2821.
  • Kroon AA, Heij JM, Kuijper WA, et al. Function and morphology of respiratory cilia in situs inversus. Clin Otolaryngol Allied Sci. 1991;16:294–297.
  • Aylsworth AS. Clinical aspects of defects in the determination of laterality. Am J Med Genet. 2001;101:345–355.
  • Lin AE, Krikov S, Riehle-Colarusso T, et al. Laterality defects in the national birth defects prevention study (1998-2007): birth prevalence and descriptive epidemiology. Am J Med Genet A. 2014;164A:2581–2591.
  • Engesaeth VG, Warner JO, Bush A. New associations of primary ciliary dyskinesia syndrome. Pediatr Pulmonol. 1993;16:9–12.
  • Shapiro AJ, Davis SD, Ferkol T, et al. Laterality defects other than situs inversus totalis in primary ciliary dyskinesia: insights into situs ambiguus and heterotaxy. Chest. 2014;146:1176–1186.
  • Wilson GR, Wang HX, Egan GF, et al. Deletion of the Parkin co-regulated gene causes defects in ependymal ciliary motility and hydrocephalus in the quakingviable mutant mouse. Hum Mol Genet. 2010;19:1593–1602.
  • Wodarczyk C, Rowe I, Chiaravalli M, et al. A novel mouse model reveals that polycystin-1 deficiency in ependyma and choroid plexus results in dysfunctional cilia and hydrocephalus. PLoS One. 2009;4:e7137.
  • Ibanez-Tallon I, Gorokhova S, Heintz N. Loss of function of axonemal dynein Mdnah5 causes primary ciliary dyskinesia and hydrocephalus. Hum Mol Genet. 2002;11:715–721.
  • Lee L. Riding the wave of ependymal cilia: genetic susceptibility to hydrocephalus in primary ciliary dyskinesia. J Neurosci Res. 2013;91:1117–1132.
  • Vieira JP, Lopes P, Silva R. Primary ciliary dyskinesia and hydrocephalus with aqueductal stenosis. J Child Neurol. 2012;27:938–941.
  • Wessels MW, den Hollander NS, Willems PJ. Mild fetal cerebral ventriculomegaly as a prenatal sonographic marker for Kartagener syndrome. Prenat Diagn. 2003;23:239–242.
  • Harden B, Tian X, Giese R, et al. Increased postoperative respiratory complications in heterotaxy congenital heart disease patients with respiratory ciliary dysfunction. J Thorac Cardiovasc Surg. 2013;147(1291–98):e2.
  • Nakhleh N, Francis R, Giese RA, et al. High prevalence of respiratory ciliary dysfunction in congenital heart disease patients with heterotaxy. Circulation. 2012;125:2232–2242.
  • Mullowney T, Manson D, Kim R, et al. Primary ciliary dyskinesia and neonatal respiratory distress. Pediatrics. 2014;134:1160–1166.
  • Coren ME, Meeks M, Morrison I, et al. Primary ciliary dyskinesia: age at diagnosis and symptom history. Acta Paediatr. 2002;91:667–669.
  • Hadfield PJ, Rowe-Jones JM, Bush A, et al. Treatment of otitis media with effusion in children with primary ciliary dyskinesia. Clin Otolaryngol Allied Sci. 1997;22:302–306.
  • Pruliere-Escabasse V, Coste A, Chauvin P, et al. Otologic features in children with primary ciliary dyskinesia. Arch Otolaryngol Head Neck Surg. 2010;136:1121–1126.
  • Pifferi M, Bush A, Caramella D, et al. Agenesis of paranasal sinuses and nasal nitric oxide in primary ciliary dyskinesia. Eur Respir J. 2011;37:566–571.
  • Boon M, Vermeulen FL, Gysemans W, et al. Lung structure-function correlation in patients with primary ciliary dyskinesia. Thorax. 2015;70:339–345.
  • Sommer JU, Schafer K, Omran H, et al. ENT manifestations in patients with primary ciliary dyskinesia: prevalence and significance of otorhinolaryngologic co-morbidities. Eur Arch Otorhinolaryngol. 2015;268:383–388.
  • Werner C, Onnebrink JG, Omran H. Diagnosis and management of primary ciliary dyskinesia. Cilia. 2015;4:2.
  • Davis SD, Ferkol TW, Rosenfeld M, et al. Clinical features of childhood primary ciliary dyskinesia by genotype and ultrastructural phenotype. Am J Respir Crit Care Med. 2015;191:316–324.
  • Afzelius BA, Eliasson R. Male and female infertility problems in the immotile-cilia syndrome. Eur J Respir Dis Suppl. 1983;127:144–147.
  • Halbert SA, Patton DL, Zarutskie PW, et al. Function and structure of cilia in the fallopian tube of an infertile woman with Kartagener’s syndrome. Hum Reprod. 1997;12:55–58.
  • Noone PG, Leigh MW, Sannuti A, et al. Primary ciliary dyskinesia: diagnostic and phenotypic features. Am J Respir Crit Care Med. 2004;169:459–467.
  • Leigh MW, Pittman JE, Carson JL, et al. Clinical and genetic aspects of primary ciliary dyskinesia/Kartagener syndrome. Genet Med. 2009;11:473–487.
  • Moua T, Zand L, Hartman RP, et al. Radiologic and clinical bronchiectasis associated with autosomal dominant polycystic kidney disease. PLoS One. 2009;9:e93674.
  • Bonneau D, Raymond F, Kremer C, et al. Usher syndrome type I associated with bronchiectasis and immotile nasal cilia in two brothers. J Med Genet. 1993;30:253–254.
  • Gunay-Aygun M, Turkbey BI, Bryant J, et al. Hepatorenal findings in obligate heterozygotes for autosomal recessive polycystic kidney disease. Mol Genet Metab. 2011;104:677–681.
  • Pawar S, Zanwar V, Mohite A, et al. A family of congenital hepatic fibrosis and atypical retinitis pigmentosa. Clin Pract. 2015;5:792.
  • Kenny T, Beales P. Ciliopathies - a reference for clinicians. Oxford: Oxford University Press; 2014.
  • Behan L, Dimitrov BD, Kuehni CE, et al. PICADAR: a diagnostic predictive tool for primary ciliary dyskinesia. Eur Respir J. 2016;47:1103–1112.
  • Pifferi M, Bush A, Maggi F, et al. Nasal nitric oxide and nitric oxide synthase expression in primary ciliary dyskinesia. Eur Respir J. 2011;37:572–577.
  • Jackson CL, Behan L, Collins SA, et al. Accuracy of diagnostic testing in primary ciliary dyskinesia. Eur Respir J. 2016;47:837–848.
  • Leigh MW, Hazucha MJ, Chawla KK, et al. Standardizing nasal nitric oxide measurement as a test for primary ciliary dyskinesia. Ann Am Thorac Soc. 2013;10:574–581.
  • Kouis P, Papatheodorou SI, Yiallouros PK. Diagnostic accuracy of nasal nitric oxide for establishing diagnosis of primary ciliary dyskinesia: a meta-analysis. BMC Pulm Med. 2015;15:153.
  • Adams PS, Tian X, Zahid M, et al. Establishing normative nasal nitric oxide values in infants. Respir Med. 2015;109:1126–1130.
  • Balfour-Lynn IM, Laverty A, Dinwiddie R. Reduced upper airway nitric oxide in cystic fibrosis. Arch Dis Child. 1996;75:319–322.
  • Thomas SR, Kharitonov SA, Scott SF, et al. Nasal and exhaled nitric oxide is reduced in adult patients with cystic fibrosis and does not correlate with cystic fibrosis genotype. Chest. 2000;117:1085–1089.
  • Nakano H, Ide H, Imada M, et al. Reduced nasal nitric oxide in diffuse panbronchiolitis. Am J Respir Crit Care Med. 2000;162:2218–2220.
  • Collins SA, Behan L, Harris A, et al. The dangers of widespread nitric oxide screening for primary ciliary dyskinesia. Thorax. 2016;71:560–561.
  • Raidt J, Wallmeier J, Hjeij R, et al. Ciliary beat pattern and frequency in genetic variants of primary ciliary dyskinesia. Eur Respir J. 2014;44:1579–1588.
  • Dougherty GW, Loges NT, Klinkenbusch JA, et al. DNAH11 localization in the proximal region of respiratory cilia defines distinct outer dynein arm complexes. Am J Respir Cell Mol Biol. 2016;55:213–224.
  • Panizzi JR, Becker-Heck A, Castleman VH, et al. CCDC103 mutations cause primary ciliary dyskinesia by disrupting assembly of ciliary dynein arms. Nat Genet. 2012;44:714–719.
  • Hirst RA, Rutman A, Williams G, et al. Ciliated air-liquid cultures as an aid to diagnostic testing of primary ciliary dyskinesia. Chest. 2010;138:1441–1447.
  • Boon M, Smits A, Cuppens H, et al. Primary ciliary dyskinesia: critical evaluation of clinical symptoms and diagnosis in patients with normal and abnormal ultrastructure. Orphanet J Rare Dis. 2014;9:11.
  • Shoemark A, Dixon M, Corrin B, et al. Twenty-year review of quantitative transmission electron microscopy for the diagnosis of primary ciliary dyskinesia. J Clin Pathol. 2012;65:267–271.
  • O’Callaghan C, Rutman A, Williams GM, et al. Inner dynein arm defects causing primary ciliary dyskinesia: repeat testing required. Eur Respir J. 2011;38:603–607.
  • Thomas B, Rutman A, Hirst RA, et al. Ciliary dysfunction and ultrastructural abnormalities are features of severe asthma. J Allergy Clin Immunol. 2010;126(722–29):e2.
  • Jorissen M, Willems T, Van der Schueren B, et al. Ultrastructural expression of primary ciliary dyskinesia after ciliogenesis in culture. Acta Otorhinolaryngol Belg. 2000;54:343–356.
  • Noone PG, Zariwala M, Sannuti A, et al. Mutations in DNAI1 (IC78) cause primary ciliary dyskinesia. Chest. 2002;121:97S.
  • Loges NT, Olbrich H, Fenske L, et al. DNAI2 mutations cause primary ciliary dyskinesia with defects in the outer dynein arm. Am J Hum Genet. 2008;83:547–558.
  • Mazor M, Alkrinawi S, Chalifa-Caspi V, et al. Primary ciliary dyskinesia caused by homozygous mutation in DNAL1, encoding dynein light chain 1. Am J Hum Genet. 2011;88:599–607.
  • Jeanson L, Copin B, Papon JF, et al. RSPH3 mutations cause primary ciliary dyskinesia with central-complex defects and a near absence of radial spokes. Am J Hum Genet. 2015;97:153–162.
  • Castleman VH, Romio L, Chodhari R, et al. Mutations in radial spoke head protein genes RSPH9 and RSPH4A cause primary ciliary dyskinesia with central-microtubular-pair abnormalities. Am J Hum Genet. 2009;84:197–209.
  • Merveille AC, Davis EE, Becker-Heck A, et al. CCDC39 is required for assembly of inner dynein arms and the dynein regulatory complex and for normal ciliary motility in humans and dogs. Nat Genet. 2011;43:72–78.
  • Becker-Heck A, Zohn IE, Okabe N, et al. The coiled-coil domain containing protein CCDC40 is essential for motile cilia function and left-right axis formation. Nat Genet. 2011;43:79–84.
  • Horani A, Brody SL, Ferkol TW, et al. CCDC65 mutation causes primary ciliary dyskinesia with normal ultrastructure and hyperkinetic cilia. PLoS One. 2013;8:e72299.
  • Olbrich H, Cremers C, Loges NT, et al. Loss-of-function GAS8 mutations cause primary ciliary dyskinesia and disrupt the nexin-dynein regulatory complex. Am J Hum Genet. 2015;97:546–554.
  • Hjeij R, Onoufriadis A, Watson CM, et al. CCDC151 mutations cause primary ciliary dyskinesia by disruption of the outer dynein arm docking complex formation. Am J Hum Genet. 2014;95:257–274.
  • Hjeij R, Lindstrand A, Francis R, et al. ARMC4 mutations cause primary ciliary dyskinesia with randomization of left/right body asymmetry. Am J Hum Genet. 2013;93:357–367.
  • Moore DJ, Onoufriadis A, Shoemark A, et al. Mutations in ZMYND10, a gene essential for proper axonemal assembly of inner and outer dynein arms in humans and flies, cause primary ciliary dyskinesia. Am J Hum Genet. 2013;93:346–356.
  • Zariwala MA, Gee HY, Kurkowiak M, et al. ZMYND10 is mutated in primary ciliary dyskinesia and interacts with LRRC6. Am J Hum Genet. 2013;93:336–345.
  • Kott E, Duquesnoy P, Copin B, et al. Loss-of-function mutations in LRRC6, a gene essential for proper axonemal assembly of inner and outer dynein arms, cause primary ciliary dyskinesia. Am J Hum Genet. 2012;91:958–964.
  • Diggle CP, Moore DJ, Mali G, et al. HEATR2 plays a conserved role in assembly of the ciliary motile apparatus. PLoS Genet. 2014;10:e1004577.
  • Austin-Tse C, Halbritter J, Zariwala MA, et al. Zebrafish ciliopathy screen plus human mutational analysis identifies C21orf59 and CCDC65 defects as causing primary ciliary dyskinesia. Am J Hum Genet. 2013;93:672–686.
  • Loges NT, Olbrich H, Becker-Heck A, et al. Deletions and point mutations of LRRC50 cause primary ciliary dyskinesia due to dynein arm defects. Am J Hum Genet. 2009;85:883–889.
  • Mitchison HM, Schmidts M, Loges NT, et al. Mutations in axonemal dynein assembly factor DNAAF3 cause primary ciliary dyskinesia. Nat Genet. 2012;44(381–9):S1–S2.
  • Casey JP, McGettigan PA, Healy F, et al. Unexpected genetic heterogeneity for primary ciliary dyskinesia in the Irish traveller population. Eur J Hum Genet. 2015;23:210–217.
  • Knowles MR, Ostrowski LE, Loges NT, et al. Mutations in SPAG1 cause primary ciliary dyskinesia associated with defective outer and inner dynein arms. Am J Hum Genet. 2013;93:711–720.
  • Duriez B, Duquesnoy P, Escudier E, et al. A common variant in combination with a nonsense mutation in a member of the thioredoxin family causes primary ciliary dyskinesia. Proc Natl Acad Sci U S A. 2007;104:3336–3341.
  • Wallmeier J, Al-Mutairi DA, Chen CT, et al. Mutations in CCNO result in congenital mucociliary clearance disorder with reduced generation of multiple motile cilia. Nat Genet. 2014;46:646–651.
  • Boon M, Wallmeier J, Ma L, et al. MCIDAS mutations result in a mucociliary clearance disorder with reduced generation of multiple motile cilia. Nat Commun. 2014;5:4418.
  • Budny B, Chen W, Omran H, et al. A novel X-linked recessive mental retardation syndrome comprising macrocephaly and ciliary dysfunction is allelic to oral-facial-digital type I syndrome. Hum Genet. 2006;120:171–178.
  • Bukowy-Bieryllo Z, Zietkiewicz E, Loges NT, et al. RPGR mutations might cause reduced orientation of respiratory cilia. Pediatr Pulmonol. 2013;48:352–363.
  • Burgoyne T, Lewis A, Dewar A, et al. Characterizing the ultrastructure of primary ciliary dyskinesia transposition defect using electron tomography. Cytoskeleton (Hoboken). 2014;71:294–301.
  • Knowles MR, Daniels LA, Davis SD, et al. Primary ciliary dyskinesia recent advances in diagnostics, genetics, and characterization of clinical disease. Am J Respir Crit Care Med. 2013;188:913–922.
  • Barbato A, Frischer T, Kuehni CE, et al. Primary ciliary dyskinesia: a consensus statement on diagnostic and treatment approaches in children. Eur Respir J. 2009;34:1264–1276.
  • Shapiro AJ, Zariwala MA, Ferkol T, et al. Diagnosis, monitoring, and treatment of primary ciliary dyskinesia: PCD foundation consensus recommendations based on state of the art review. Pediatr Pulmonol. 2016;51:115–132.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.