Abstract
Primary ciliary dyskinesia (PCD) is a rare autosomal recessive disease, caused by specific primary structural and/or functional abnormalities of the motile cilia, in contrast with the transitory abnormalities seen in secondary ciliary dyskinesia. Disease-causing mutations in at least 16 genes have already been identified. The true incidence of PCD may be higher than currently reported, because the diagnosis is challenging and often missed. For the confirmation of PCD, both ciliary motility as well as ciliary ultrastructure must be evaluated. An early and adequate diagnosis and therapy can theoretically prevent bronchiectasis. Measurement of nasal nitric oxide has some value as a screening test but cannot be performed in young children. In the respiratory tract epithelium, impaired mucociliary clearance leads to chronic and/or recurrent upper and lower respiratory tract infections. In up to 75 % of the patients, respiratory manifestations start in the newborn period, although the diagnosis is often missed at that time. During embryogenesis, nodal cilia, which are motile cilia, determine the correct lateralization of the organs. Dysfunction of these cilia leads to random lateralization and thus situs inversus in approximately 50 % of the patients with PCD. The tail of a spermatozoon has a structure similar to that of a motile cilium. Consequently, male infertility due to immotile spermatozoa is often part of the characteristics of PCD. Given the heterogeneity and the rarity of the disorder, therapy is not evidence-based. Many treatment schedules are proposed in analogy with the treatment for cystic fibrosis.
Conclusion
Respiratory infections, situs inversus and male infertility are typical manifestations of PCD, a rare autosomal recessive disorder.
Abbreviations
- CBF:
-
Ciliary beat frequency
- CF:
-
Cystic fibrosis
- CFTR:
-
Cystic fibrosis transmembrane conductance regulator
- DNAH:
-
Dynein axonemal heavy chain
- DNAI:
-
Dynein axonemal intermediate chain
- DNAL:
-
Dynein axonemal light chain
- ENT:
-
Ear nose and throat
- HRCT:
-
High-resolution computed tomography
- IDA:
-
Inner dynein arm
- IVF:
-
In vitro fertilization
- nNO:
-
Nasal nitric oxide
- NO:
-
Nitric oxide
- ODA:
-
Outer dynein arm
- OME:
-
Otitis media with effusion
- PCD:
-
Primary ciliary dyskinesia
- SCD:
-
Secondary ciliary dyskinesia
- SI:
-
Situs inversus
- TEM:
-
Transmission electron microscopy
References
Abu-Musa A, Nassar A, Usta I (2008) In vitro fertilization in two patients with Kartagener's syndrome and infertility. Gynecol Obstet Invest 65(1):29–31
Afzelius BA (1976) A human syndrome caused by immotile cilia. Science 193(4250):317–319
Amirav I, Cohen-Cymberknoh M, Shoseyov D, Kerem E (2009) Primary ciliary dyskinesia: prospects for new therapies, building on the experience in cystic fibrosis. Paediatr Respir Rev 10(2):58–62
ATS Workshop Proceedings: Exhaled nitric oxide and nitric oxide oxidative metabolism in exhaled breath condensate: executive summary (2006). American journal of respiratory and critical care medicine 173 (7):811-813
ATS/ERS recommendations for standardized procedures for the online and off-line measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide, 2005 (2005). Am J Respir Crit Care Med 171 (8):912-930
Barbato A, Frischer T, Kuehni CE, Snijders D, Azevedo I et al (2009) Primary ciliary dyskinesia: a consensus statement on diagnostic and treatment approaches in children. Eur Respir J 34(6):1264–1276
Bartoloni L, Blouin JL, Pan Y, Gehrig C, Maiti AK et al (2002) Mutations in the DNAH11 (axonemal heavy chain dynein type 11) gene cause one form of situs inversus totalis and most likely primary ciliary dyskinesia. Proc Natl Acad Sci U S A 99(16):10282–10286
Becker-Heck A, Zohn IE, Okabe N, Pollock A, Lenhart KB et al (2011) The coiled-coil domain containing protein CCDC40 is essential for motile cilia function and left–right axis formation. Nat Genet 43(1):79–84
Bougioukas I, Mikroulis D, Danner B, Lawal L, Eleftheriadis S et al (2010) Coronary artery bypass surgery in a patient with Kartagener syndrome: a case report and literature review. J Cardiothorac Surg 5:68
Brown DE, Pittman JE, Leigh MW, Fordham L, Davis SD (2008) Early lung disease in young children with primary ciliary dyskinesia. Ped Pulmonol 43(5):514–516
Brueckner M (2007) Heterotaxia, congenital heart disease, and primary ciliary dyskinesia. Circ 115(22):2793–2795
Budny B, Chen W, Omran H, Fliegauf M, Tzschach A et al (2006) A novel X-linked recessive mental retardation syndrome comprising macrocephaly and ciliary dysfunction is allelic to oral–facial–digital type I syndrome. Hum Genet 120(2):171–178
Bush A (1998) Congenital heart disease in primary ciliary dyskinesia. Pediatr Cardiol 19(2):191
Bush A, Chodhari R, Collins N, Copeland F, Hall P et al (2007) Primary ciliary dyskinesia: current state of the art. Arch Dis Child 92(12):1136–1140
Bush A, Cole P, Hariri M, Mackay I, Phillips G et al (1998) Primary ciliary dyskinesia: diagnosis and standards of care. Eur Respir J 4:982–988
Campbell R (2012) Managing upper respiratory tract complications of primary ciliary dyskinesia in children. Curr Opin Allergy Clin Immunol 12(1):32–38
Campbell RG, Birman CS, Morgan L (2009) Management of otitis media with effusion in children with primary ciliary dyskinesia: a literature review. Int J Pediatr Otorhinolaryngol 73(12):1630–1638
Castleman VH, Romio L, Chodhari R, Hirst RA, de Castro SC et al (2009) Mutations in radial spoke head protein genes RSPH9 and RSPH4A cause primary ciliary dyskinesia with central-microtubular-pair abnormalities. Am J Med Genet 84(2):197–209
Ceccaldi PF, Carre-Pigeon F, Youinou Y, Delepine B, Bryckaert PE et al (2004) Kartagener's syndrome and infertility: observation, diagnosis and treatment. J Gynecol Obstet Biol Reprod (Paris) 33(3):192–194
Chhin B, Negre D, Merrot O, Pham J, Tourneur Y et al (2009) Ciliary beating recovery in deficient human airway epithelial cells after lentivirus ex vivo gene therapy. PLoS Genet 5(3):e1000422
Chilvers MA, Rutman A, O'Callaghan C (2003) Ciliary beat pattern is associated with specific ultrastructural defects in primary ciliary dyskinesia. J Allergy Clin Immunol 112(3):518–524
Colantonio D, Brouillette L, Parikh A, Scadding GK (2002) Paradoxical low nasal nitric oxide in nasal polyposis. Clin Exp Allergy 32(5):698–701
Corbeel L, Cornillie F, Lauweryns J, Boel M, van den Berghe G (1981) Ultrastructural abnormalities of bronchial cilia in children with recurrent airway infections and bronchiectasis. Arch Dis Child 56(12):929–933
Coren ME, Meeks M, Morrison I, Buchdahl RM, Bush A (2002) Primary ciliary dyskinesia: age at diagnosis and symptom history. Acta Paediatr 91(6):667–669
De Boeck K, Proesmans M, Mortelmans L, Van Billoen B, Willems T et al (2005) Mucociliary transport using 99mTc-albumin colloid: a reliable screening test for primary ciliary dyskinesia. Thorax 60(5):414–417
De Santi MM, Magni A, Valletta EA, Gardi C, Lungarella G (1990) Hydrocephalus, bronchiectasis, and ciliary aplasia. Arch Dis Child 65(5):543–544
Degano B, Valmary S, Serrano E, Brousset P, Arnal JF (2011) Expression of nitric oxide synthases in primary ciliary dyskinesia. Hum Pathol 42:1855–1861
Devalia JL, Sapsford RJ, Rusznak C, Toumbis MJ, Davies RJ (1992) The effects of salmeterol and salbutamol on ciliary beat frequency of cultured human bronchial epithelial cells, in vitro. Pulm Pharmacol 5(4):257–263
Driscoll JA, Bhalla S, Liapis H, Ibricevic A, Brody SL (2008) Autosomal dominant polycystic kidney disease is associated with an increased prevalence of radiographic bronchiectasis. Chest 133(5):1181–1188
Duriez B, Duquesnoy P, Escudier E, Bridoux AM, Escalier D et al (2007) 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 104(9):3336–3341
El-Abiad NM, Clifton S, Nasr SZ (2007) Long-term use of nebulized human recombinant DNase1 in two siblings with primary ciliary dyskinesia. Respir Med 101(10):2224–2226
Eliasson R, Mossberg B, Camner P, Afzelius BA (1977) The immotile-cilia syndrome. A congenital ciliary abnormality as an etiologic factor in chronic airway infections and male sterility. N Eng J Med 297(1):1–6
Ellerman A, Bisgaard H (1997) Longitudinal study of lung function in a cohort of PCD. Eur Respir J 10:2376–2379
Escudier E, Couprie M, Duriez B, Roudot-Thoraval F, Millepied MC et al (2002) Computer-assisted analysis helps detect inner dynein arm abnormalities. Am J Respir Crit Care Med 166(9):1257–1262
Failly M, Bartoloni L, Letourneau A, Munoz A, Falconnet E et al (2009) Mutations in DNAH5 account for only 15 % of a non-preselected cohort of patients with primary ciliary dyskinesia. J Med Genet 46(4):281–286
Fauroux B, Tamalet A, Clement A (2009) Management of primary ciliary dyskinesia: the lower airways. Paediatr Respir Rev 10(2):55–57
Ferkol T, Leigh M (2006) Primary ciliary dyskinesia and newborn respiratory distress. Semin Perinatol 30(6):335–340
Fliegauf M, Olbrich H, Horvath J, Wildhaber JH, Zariwala MA et al (2005) Mislocalization of DNAH5 and DNAH9 in respiratory cells from patients with primary ciliary dyskinesia. Am J Respir Crit Care Med 171(12):1343–1349
Gentile DA, Doyle WJ, Belenky S, Ranck H, Angelini B et al (2002) Nasal and oral nitric oxide levels during experimental respiratory syncytial virus infection of adults. Acta Otolaryngol 122(1):61–66
Grasemann H, Gartig SS, Wiesemann HG, Teschler H, Konietzko N et al (1999) Effect of l-arginine infusion on airway NO in cystic fibrosis and primary ciliary dyskinesia syndrome. Eur Respir J 13(1):114–118
Greenstone MA, Jones RW, Dewar A, Neville BG, Cole PJ (1984) Hydrocephalus and primary ciliary dyskinesia. Arch Dis Child 59(5):481–482
Guichard C, Harricane MC, Lafitte JJ, Godard P, Zaegel M et al (2001) Axonemal dynein intermediate-chain gene (DNAI1) mutations result in situs inversus and primary ciliary dyskinesia (Kartagener syndrome). Am J Hum Genet 68(4):1030–1035
Halbert SA, Patton DL, Zarutskie PW, Soules MR (1997) Function and structure of cilia in the fallopian tube of an infertile woman with Kartagener's syndrome. Hum Reprod 12(1):55–58
Hattori H, Nakajo Y, Ito C, Toyama Y, Toshimori K et al (2011) Birth of a healthy infant after intracytoplasmic sperm injection using pentoxifylline-activated sperm from a patient with Kartagener's syndrome. Fertil Steril 95(7):2431, e2439-2411
Hellinckx J, Demedts M, De Boeck K (1998) PCD, evolution of pulmonary function. Eur J Pediatr 157:422–426
Hildebrandt F, Benzing T, Katsanis N (2011) Ciliopathies. N Engl J Med 364(16):1533–1543
Homma S, Kawabata M, Kishi K, Tsuboi E, Narui K et al (1999) Bronchiolitis in Kartagener's syndrome. Eur Respir J 14(6):1332–1339
Hornef N, Olbrich H, Horvath J, Zariwala MA, Fliegauf M et al (2006) DNAH5 mutations are a common cause of primary ciliary dyskinesia with outer dynein arm defects. Am J Respir Crit Care Med 174(2):120–126
Horvath I, Loukides S, Wodehouse T, Csiszer E, Cole PJ et al (2003) Comparison of exhaled and nasal nitric oxide and exhaled carbon monoxide levels in bronchiectatic patients with and without primary ciliary dyskinesia. Thorax 58(1):68–72
Horvath J, Fliegauf M, Olbrich H, Kispert A, King SM et al (2005) Identification and analysis of axonemal dynein light chain 1 in primary ciliary dyskinesia patients. Am J Respir Cell Mol Biol 33(1):41–47
Ichioka K, Kohei N, Okubo K, Nishiyama H, Terai A (2006) Obstructive azoospermia associated with chronic sinopulmonary infection and situs inversus totalis. Urol 68(1):204, e205-207
Jorissen M, Willems T, Van der Schueren B (2000) Ciliary function analysis for the diagnosis of primary ciliary dyskinesia: advantages of ciliogenesis in culture. Acta Otolaryngol 120(2):291–295
Jorissen M, Willems T, Van der Schueren B, Verbeken E, De Boeck K (2000) Ultrastructural expression of primary ciliary dyskinesia after ciliogenesis in culture. Acta Otorhinolaryngol Belg 54(3):343–356
Kartagener M (1933) Zur Pathogenese der Bronchiektasien. Beitr Klin Tuberk 83:489–501
Kay VJ, Irvine DS (2000) Successful in-vitro fertilization pregnancy with spermatozoa from a patient with Kartagener's syndrome: case report. Hum Reprod 15(1):135–138
Kennedy MP, Noone PG, Carson J, Molina PL, Ghio A et al (2007) Calcium stone lithoptysis in primary ciliary dyskinesia. Respir Med 101(1):76–83
Kennedy MP, Noone PG, Leigh MW, Zariwala MA, Minnix SL et al (2007) High-resolution CT of patients with primary ciliary dyskinesia. AJR Am J Roentgenol 188(5):1232–1238
Kennedy MP, Omran H, Leigh MW, Dell S, Morgan L et al (2007) Congenital heart disease and other heterotaxic defects in a large cohort of patients with primary ciliary dyskinesia. Circ 115(22):2814–2821
Knowles MR, Leigh MW, Carson JL, Davis SD, Dell SD et al (2011) Mutations of DNAH11 in patients with primary ciliary dyskinesia with normal ciliary ultrastructure. Thorax 67:433–441
Koh YY, Park Y, Jeong JH, Kim CK, Min YG et al (2000) The effect of regular salbutamol on lung function and bronchial responsiveness in patients with primary ciliary dyskinesia. Chest 117(2):427–433
Krawczynski MR, Dmenska H, Witt M (2004) Apparent X-linked primary ciliary dyskinesia associated with retinitis pigmentosa and a hearing loss. J Appl Genet 45(1):107–110
Kuehni CE, Frischer T, Strippoli MP, Maurer E, Bush A et al (2010) Factors influencing age at diagnosis of primary ciliary dyskinesia in European children. Eur Respir J 36(6):1248–1258
Lefevere L, Willems T, Lindberg S, Jorissen M (2000) Nasal nitric oxide. Acta Otorhinolaryngol Belg 54(3):271–280
Leigh MW, Pittman JE, Carson JL, Ferkol TW, Dell SD et al (2009) Clinical and genetic aspects of PCD. Kartagener Genet Med 11(7):473–487
Lie H, Ferkol T (2007) Primary ciliary dyskinesia: recent advances in pathogenesis, diagnosis and treatment. Drugs 67(13):1883–1892
Lindberg S, Cervin A, Runer T (1997) Nitric oxide (NO) production in the upper airways is decreased in chronic sinusitis. Acta Otolaryngol 117(1):113–117
Loges NT, Olbrich H, Becker-Heck A, Haffner K, Heer A et al (2009) Deletions and point mutations of LRRC50 cause primary ciliary dyskinesia due to dynein arm defects. Am J Hum Genet 85(6):883–889
Loges NT, Olbrich H, Fenske L, Mussaffi H, Horvath J et al (2008) DNAI2 mutations cause primary ciliary dyskinesia with defects in the outer dynein arm. Am J Hum Genet 83(5):547–558
Lucas JSA, Walker WT, Kuehni CE, Lazor R (2011) Primary ciliary dyskinesia. Eur Respir Monograph 54:201–217
Lundberg JO, Weitzberg E, Nordvall SL, Kuylenstierna R, Lundberg JM et al (1994) Primarily nasal origin of exhaled nitric oxide and absence in Kartagener's syndrome. Eur Respir J 7(8):1501–1504
Maglione M, Bush A, Montella S, Mollica C, Manna A et al (2011) Progression of lung disease in primary ciliary dyskinesia: is spirometry less accurate than CT? Ped Pulmonol 47(5):498–504
Majithia A, Fong J, Hariri M, Harcourt J (2005) Hearing outcomes in children with primary ciliary dyskinesia-a longitudinal study. Int J Pediatr Otorhinolaryngol 69(8):1061–1064
Maniscalco M, Sofia M, Pelaia G (2007) Nitric oxide in upper airways inflammatory diseases. Inflamm Res 56(2):58–69
Marshall WF (2008) The cell biological basis of ciliary disease. J Cell Biol 180(1):17–21
Marthin JK, Mortensen J, Pressler T, Nielsen KG (2007) Pulmonary radioaerosol mucociliary clearance in diagnosis of primary ciliary dyskinesia. Chest 132(3):966–976
Marthin JK, Nielsen KG (2011) Choice of nasal nitric oxide technique as first-line test for primary ciliary dyskinesia. Eur Respir J 37(3):559–565
Marthin JK, Petersen N, Skovgaard LT, Nielsen KG (2010) Lung function in patients with primary ciliary dyskinesia: a cross-sectional and 3-decade longitudinal study. Am J Respir Crit Care Med 181(11):1262–1268
Mateos-Corral D, Coombs R, Grasemann H, Ratjen F, Dell SD (2011) Diagnostic value of nasal nitric oxide measured with non-velum closure techniques for children with primary ciliary dyskinesia. J Pediatr 159(3):420–424
Mazor M, Alkrinawi S, Chalifa-Caspi V, Manor E, Sheffield VC et al (2011) Primary ciliary dyskinesia caused by homozygous mutation in DNAL1, encoding dynein light chain 1. Am J Hum Genet 88(5):599–607
McManus IC, Mitchison HM, Chung EM, Stubbings GF, Martin N (2003) Primary ciliary dyskinesia (Siewert's/Kartagener's syndrome): respiratory symptoms and psycho-social impact. BMC Pulm Med 3:4
Merveille AC, Davis EE, Becker-Heck A, Legendre M, Amirav I et al (2011) 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 43(1):72–78
Mitchison HM, Schmidts M, Loges NT, Freshour J, Dritsoula A et al (2012) Mutations in axonemal dynein assembly factor DNAAF3 cause primary ciliary dyskinesia. Nat Genet 44(4):381–9
Moore A, Escudier E, Roger G, Tamalet A, Pelosse B et al (2006) RPGR is mutated in patients with a complex X-linked phenotype combining primary ciliary dyskinesia and retinitis pigmentosa. J Med Genet 43(4):326–333
Munro NC, Currie DC, Lindsay KS, Ryder TA, Rutman A et al (1994) Fertility in men with primary ciliary dyskinesia presenting with respiratory infection. Thorax 49(7):684–687
Nadel HR, Stringer DA, Levison H, Turner JA, Sturgess JM (1985) The immotile cilia syndrome: radiological manifestations. Radiol 154(3):651–655
Nakano H, Ide H, Imada M, Osanai S, Takahashi T et al (2000) Reduced nasal nitric oxide in diffuse panbronchiolitis. Am J Respir Crit Care Med 162:2218–2220
Narang I, Ersu R, Wilson NM, Bush A (2002) Nitric oxide in chronic airway inflammation in children, diagnostic use and pathophysiological significance. Thorax 57:586–589
Narayan D, Krishnan SN, Upender M, Ravikumar TS, Mahoney MJ et al (1994) Unusual inheritance of primary ciliary dyskinesia (Kartagener's syndrome). J Med Genet 31(6):493–496
Noone PG, Bennett WD, Regnis JA, Zeman KL, Carson JL et al (1999) Effect of aerosolized uridine-5′-triphosphate on airway clearance with cough in patients with primary ciliary dyskinesia. Am J Respir Crit Care Med 160(1):144–149
Noone PG, Leigh MW, Sannuti A, Minnix SL, Carson JL et al (2004) Primary ciliary dyskinesia: diagnostic and phenotypic features. Am J Respir Crit Care Med 169(4):459–467
O'Callaghan C, Chilvers M, Hogg C, Bush A, Lucas J (2007) Diagnosing primary ciliary dyskinesia. Thorax 62(8):656–657
Olbrich H, Haffner K, Kispert A, Volkel A, Volz A et al (2002) Mutations in DNAH5 cause primary ciliary dyskinesia and randomization of left–right asymmetry. Nat Genet 30(2):143–144
Omran H, Kobayashi D, Olbrich H, Tsukahara T, Loges NT et al (2008) Ktu/PF13 is required for cytoplasmic pre-assembly of axonemal dyneins. Nature 456(7222):611–616
Panizzi JR, Becker-Heck A, Castleman VH, Al-Mutairi DA, Liu Y et al (2012) CCDC103 mutations cause primary ciliary dyskinesia by disrupting assembly of ciliary dynein arms. Nat Genet 44(6):714–9
Pennarun G, Escudier E, Chapelin C, Bridoux AM, Cacheux V et al (1999) Loss-of-function mutations in a human gene related to Chlamydomonas reinhardtii dynein IC78 result in primary ciliary dyskinesia. Am J Hum Genet 65(6):1508–1519
Phillips GE, Thomas S, Heather S, Bush A (1998) Airway response of children with primary ciliary dyskinesia to exercise and beta2-agonist challenge. Eur Respir J 11(6):1389–1391
Piacentini GL, Bodini A, Peroni DG, Sandri M, Brunelli M et al (2010) Nasal nitric oxide levels in healthy pre-school children. Pediatr Allergy Immunol 21(8):1139–1145
Pifferi M, Bush A, Caramella D, Di Cicco M, Zangani M et al (2011) Agenesis of paranasal sinuses and nasal nitric oxide in primary ciliary dyskinesia. Eur Respir J 37(3):566–571
Pifferi M, Bush A, Di Cicco M, Pradal U, Ragazzo V et al (2010) Health-related quality of life and unmet needs in patients with primary ciliary dyskinesia. Eur Respir J 35(4):787–794
Pifferi M, Bush A, Maggi F, Michelucci A, Ricci V et al (2011) Nasal nitric oxide and nitric oxide synthase expression in primary ciliary dyskinesia. Eur Respir J 37(3):572–577
Pifferi M, Cangiotti AM, Ragazzo V, Baldini G, Cinti S et al (2001) Primary ciliary dyskinesia: diagnosis in children with inconclusive ultrastructural evaluation. Pediatr Allergy Immunol 12(5):274–282
Pifferi M, Caramella D, Cangiotti AM, Ragazzo V, Macchia P et al (2007) Nasal nitric oxide in atypical primary ciliary dyskinesia. Chest 131(3):870–873
Pifferi M, Michelucci A, Conidi ME, Cangiotti AM (2010) New DNAH11 mutations in PCD with normal axonemal ultrastructure. Eur Respir J 35(6):1413–1416
Pruliere-Escabasse V, Coste A, Chauvin P, Fauroux B, Tamalet A et al (2010) Otologic features in children with primary ciliary dyskinesia. Arch Otolaryngol Head Neck Surg 136(11):1121–1126
Ramsey BW, Davies J, McElvaney NG, Tullis E, Bell SC et al (2011) A CFTR potentiator in patients with cystic fibrosis and the G551D mutation. N Eng J Med 365(18):1663–1672
Rott HD (1979) Kartagener's syndrome and the syndrome of immotile cilia. Hum Genet 46(3):249–261
Sanders SP, Proud D, Permutt S, Siekierski ES, Yachechko R et al (2004) Role of nasal nitric oxide in the resolution of experimental rhinovirus infection. J Allergy Clin Immunol 113(4):697–702
Schwabe GC, Hoffmann K, Loges NT, Birker D, Rossier C et al (2008) Primary ciliary dyskinesia associated with normal axoneme ultrastructure is caused by DNAH11 mutations. Hum Mutat 29(2):289–298
Siewart A (1904) Über einem fall von bronchiektasis bei einem patient mit situs inversus viscerum. Klin Wschr 41:139–141
Smit HJ, Schreurs AJ, Van den Bosch JM, Westermann CJ (1996) Is resection of bronchiectasis beneficial in patients with primary ciliary dyskinesia? Chest 109(6):1541–1544
Sommer JU, Schafer K, Omran H, Olbrich H, Wallmeier J et al (2011) ENT manifestations in patients with primary ciliary dyskinesia: prevalence and significance of otorhinolaryngologic comorbidities. Eur Arch Otorhinolaryngol 268(3):383–388
Strippoli MP, Frischer T, Barbato A, Snijders D, Maurer E et al (2012) Management of primary ciliary dyskinesia in European children: recommendations and clinical practice. Eur Respir J 39(6):1482–1491
Swisher M, Jonas R, Tian X, Lee ES, Lo CW et al (2011) Increased postoperative and respiratory complications in patients with congenital heart disease associated with heterotaxy. J Thorac Cardiovasc Surg 141(3):637–644, 644 e631-633
Tkebuchava T, von Segesser LK, Niederhauser U, Bauersfeld U, Turina M (1997) Cardiac surgery for Kartagener syndrome. Pediatr Cardiol 18(1):72–73
Valerio G, Giallauria F, Montella S, Vaino N, Vigorito C et al (2011) Cardiopulmonary assessment in primary ciliary dyskinesia. Eur J Clin Invest 42(6):617–22
Verdugo P, Johnson T, Tam PY (1980) Beta-adrenergic stimulation of respiratory ciliary activity. J Appl Physiol 48:868–871
Vieira JP, Lopes P, Silva R (2012) Primary ciliary dyskinesia and hydrocephalus with acqueductal stenosis. J Child Neurol. Doi: 10.1177/0883073811429856
Walker WT, Jackson CL, Lackie PM, Hogg C, Lucas JS (2012) Nitric oxide in primary ciliary dyskinesia. Eur Respir J. Doi: 10.1183/09031936.00176111
Wanner A, Salathe M, O'Riordan TG (1996) Mucociliary clearance in the airways. Am J Respir Crit Care Med 154(6 Pt 1):1868–1902
Whalley S, McManus IC (2006) Living with primary ciliary dyskinesia: a prospective qualitative study of knowledge sharing, symptom concealment, embarrassment, mistrust, and stigma. BMC Pulm Med 6:25
Yoshioka D, Sakamoto N, Ishimatsu Y, Kakugawa T, Ishii H et al (2010) Primary ciliary dyskinesia that responded to long-term, low-dose clarithromycin. Intern Med 49(14):1437–1440
Zariwala M, Noone PG, Sannuti A, Minnix S, Zhou Z et al (2001) Germline mutations in an intermediate chain dynein cause primary ciliary dyskinesia. Am J Respir Cell Mol Biol 25(5):577–583
Zariwala MA, Leigh MW, Ceppa F, Kennedy MP, Noone PG et al (2006) Mutations of DNAI1 in primary ciliary dyskinesia: evidence of founder effect in a common mutation. Am J Respir Crit Care Med 174(8):858–866
Zhu L, Belmont JW, Ware SM (2006) Genetics of human heterotaxias. Eur J Hum Genet 14(1):17–25
Zietkiewicz E, Bukowy-Bieryllo Z, Voelkel K, Klimek B, Dmenska H et al (2012) Mutations in radial spoke head genes and ultrastructural cilia defects in East-European cohort of primary ciliary dyskinesia patients. PLoS One 7(3):e33667
Conflict of interest
The authors declare that there is no conflict of interest.
Author information
Authors and Affiliations
Corresponding author
Additional information
This overview is dedicated to the late professor L. Corbeel, former editor of this journal.
Rights and permissions
About this article
Cite this article
Boon, M., Jorissen, M., Proesmans, M. et al. Primary ciliary dyskinesia, an orphan disease. Eur J Pediatr 172, 151–162 (2013). https://doi.org/10.1007/s00431-012-1785-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00431-012-1785-6