'''Primary ciliary dyskinesia''' ('''PCD'''), is a rare, [[ciliopathy|ciliopathic]], [[autosome|autosomal]] [[dominance (genetics)|recessive]] [[genetic disorder]] that causes defects in the action of [[cilia]] lining the [[respiratory tract]] (lower and upper, [[sinuses]], [[Eustachian tube]], [[middle ear]]), [[fallopian tube]], and [[flagellum]] of [[sperm]] cells. The phrase "immotile ciliary syndrome" is no longer favored as the cilia do have movement, but are merely inefficient or unsynchronized.
| treatment = Chest physiotherapy, antibiotics, supportive care, surgical interventions
| medication = Antibiotics, mucolytics
| prognosis = Variable; good management can improve quality of life
| frequency = Approximately 1 in 10,000 to 1 in 20,000 births
}}
'''Primary ciliary dyskinesia''' ('''PCD''') is a rare, [[Ciliopathy|ciliopathic]] [[autosomal recessive]] [[genetic disorder]] characterized by abnormal function of [[cilia]], the microscopic hair-like structures lining various organs such as the [[respiratory tract]], [[sinuses]], [[Eustachian tube]], [[middle ear]], and reproductive organs. Historically termed "immotile cilia syndrome," the term is no longer preferred, as the cilia retain movement, although their action is typically inefficient or unsynchronized.
Respiratory [[epithelium|epithelial]] [[Cilia#Types and distribution|motile cilia]], which resemble microscopic "hairs" (although structurally and biologically unrelated to [[hair]]), are complex [[organelle]]s that beat synchronously in the respiratory tract, moving mucus toward the throat. Normally, cilia beat 7 to 22 times per second, and any impairment can result in poor [[mucociliary clearance]], with subsequent upper and lower respiratory infection. Cilia also are involved in other biological processes (such as [[nitric oxide]] production), currently the subject of dozens of research efforts.
== Pathophysiology ==
PCD is caused by genetic mutations that affect the structure and function of [[motile cilia]]. Normally, these cilia beat synchronously 7 to 22 times per second, facilitating mucus clearance through the [[mucociliary escalator]]. Dysfunctional cilia result in impaired mucus clearance, causing recurrent infections and chronic inflammation.
==Signs and symptoms==
== Signs and symptoms ==
[[Image:Primary ciliary dyskinesia-12.jpg|thumb|Sagittal CT image showing "tree in bud" appearance of mucous impaction in distal small airways related to primary ciliary dyskinesia.]]
[[File:Primary ciliary dyskinesia-1.jpg|thumb|CT scan demonstrating [[bronchiectasis]] in PCD (Kartagener syndrome)]]
[[File:Primary ciliary dyskinesia-6.jpg|thumb|Sagittal CT showing cylindrical bronchiectasis in lower lung lobes in PCD patient]]
[[Image:Primary ciliary dyskinesia-1.jpg|thumb|CT image showing dilated and thickened medium-sized airways (bronchiectasis) in a patient with Kartagener syndrome.]]
The primary symptoms of PCD result from impaired mucus clearance and chronic respiratory infections. Symptoms usually begin early in childhood and can include:
[[Image:Primary ciliary dyskinesia-6.jpg|thumb|Oblique sagittal CT image showing lower lobe cylindrical bronchiectasis in the same patient.]]
* Chronic cough with excessive mucus production
The main consequence of impaired ciliary function is reduced or absent [[mucus]] clearance from the [[lung]]s, and susceptibility to chronic recurrent respiratory infections, including [[sinusitis]], [[bronchitis]], [[pneumonia]], and [[otitis media]]. Progressive damage to the respiratory system is common, including progressive bronchiectasis beginning in early childhood, and sinus disease (sometimes becoming severe in adults). However, diagnosis is often missed early in life despite the characteristic signs and symptoms.<ref name=pmid12162599>{{cite journal |doi=10.1080/080352502760069089 |pmid=12162599 |title=Primary ciliary dyskinesia: Age at diagnosis and symptom history |journal=Acta Paediatrica |volume=91 |issue=6 |pages=667–9 |year=2002 |last1=Coren |first1=M. E |last2=Meeks |first2=M |last3=Morrison |first3=I |last4=Buchdahl |first4=R. M |last5=Bush |first5=A }}</ref> In males, immotility of sperm can lead to [[infertility]], although conception remains possible through the use of [[in vitro fertilization]], there also are reported cases where sperm were able to move.<ref>http://www.pcdsupport.org.uk/index.php/faqs/will_it_be_difficult_to_have_children/{{full citation needed|date=March 2018}}</ref> Trials have also shown that there is a marked reduction in fertility in female sufferers of Kartagener's Syndrome due to dysfunction of the oviductal cilia.<ref name=pmid3488922>{{cite journal |pmid=3488922 |year=1986 |last1=McComb |first1=P |title=The oviductal cilia and Kartagener's syndrome |journal=Fertility and Sterility |volume=46 |issue=3 |pages=412–6 |last2=Langley |first2=L |last3=Villalon |first3=M |last4=Verdugo |first4=P |doi=10.1016/S0015-0282(16)49578-6 }}</ref>
* Recurrent [[sinusitis]] and nasal congestion
* Frequent ear infections ([[otitis media]]) leading to potential hearing loss
* Recurrent [[bronchitis]] and [[pneumonia]]
* Progressive development of [[bronchiectasis]]—permanent dilation and damage to the airways
* Reduced lung function over time
Many affected individuals experience [[hearing loss]] and show symptoms of [[otitis media]] which demonstrates variable responsiveness to the insertion of [[myringotomy]] tubes or [[grommet]]s. Some patients have a poor sense of smell, which is believed to accompany high [[mucus]] production in the sinuses (although others report normal - or even acute - sensitivity to smell and taste). Clinical progression of the disease is variable, with [[organ transplant|lung transplantation]] required in severe cases. Susceptibility to infections can be drastically reduced by an early diagnosis. Treatment with various chest physiotherapy techniques has been observed to reduce the incidence of lung infection and to slow the progression of bronchiectasis dramatically. Aggressive treatment of sinus disease beginning at an early age is believed to slow long-term sinus damage (although this has not yet been adequately documented). Aggressive measures to enhance clearance of mucus, prevent respiratory infections, and treat bacterial superinfections have been observed to slow lung-disease progression. Although the true incidence of the disease is unknown, it is estimated to be 1 in 32,000,<ref name=pmid15170433>{{cite journal |pmid=15170433 |url=http://www.masson.fr/masson/S0368-2315(04)96439-3 |year=2004 |last1=Ceccaldi |first1=P. F |title=Kartagener's syndrome and infertility: Observation, diagnosis and treatment |journal=Journal de Gynecologie, Obstetrique et Biologie de la Reproduction |volume=33 |issue=3 |pages=192–4 |last2=Carré-Pigeon |first2=F |last3=Youinou |first3=Y |last4=Delépine |first4=B |last5=Bryckaert |first5=P. E |last6=Harika |first6=G |last7=Quéreux |first7=C |last8=Gaillard |first8=D |doi=10.1016/S0368-2315(04)96439-3 }}</ref> although the actual incidence may be as high as 1 in 15,000.
Non-respiratory symptoms include:
==Genetics==
* [[Infertility]] due to impaired ciliary function in the reproductive tract:
PCD is a genetically [[Genetic heterogeneity|heterogeneous]] disorder affecting [[Motility|motile]] cilia<ref name=pmid15222957>{{cite journal |doi=10.1016/j.prrv.2003.09.005 |pmid=15222957 |title=Cilia, primary ciliary dyskinesia and molecular genetics |journal=Paediatric Respiratory Reviews |volume=5 |issue=1 |pages=69–76 |year=2004 |last1=Chodhari |first1=R |last2=Mitchison |first2=H.M |last3=Meeks |first3=M }}</ref> which are made up of approximately 250 proteins.<ref>{{cite web | title=Primary Ciliary Dyskinesia | url=http://www.genetests.org/servlet/access?db=geneclinics&site=gt&id=8888890&key=ujnJJL1T9E6XN&gry=&fcn=y&fw=8zBM&filename=/profiles/pcd/index.html | author=GeneReviews | accessdate=2007-11-16 }}</ref> Around 90%<ref name=pmid17059358>{{cite journal |doi=10.1146/annurev.physiol.69.040705.141301 |pmid=17059358 |title=Genetic Defects in Ciliary Structure and Function |journal=Annual Review of Physiology |volume=69 |pages=423–50 |year=2007 |last1=Zariwala |first1=Maimoona A |last2=Knowles |first2=Michael R |last3=Omran |first3=Heymut }}</ref> of individuals with PCD have ultrastructural defects affecting protein(s) in the outer and/or inner [[dynein]] arms, which give cilia their motility, with roughly 38%<ref name=pmid17059358/> of these defects caused by mutations on two genes, [[DNAI1]] and [[DNAH5]], both of which code for proteins found in the ciliary outer dynein arm.
** Male infertility related to immotile [[sperm]] flagella
** Female infertility or increased risk of ectopic pregnancy due to impaired cilia in the [[fallopian tubes]]
There is an international effort to identify genes that code for inner dynein arm proteins or proteins from other ciliary structures (radial spokes, central apparatus, etc.) associated with PCD.{{Citation needed|date=December 2009}} The role of DNAH5 in [[heterotaxy]] syndromes and left-right asymmetry is also under investigation. At least 32 genes have been implicated in this condition.<ref name=Zariwala2015>Zariwala MA, Knowles MR, Leigh MW (2015) [https://www.ncbi.nlm.nih.gov/books/NBK1122/ Primary Ciliary Dyskinesia]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A, editors. GeneReviews. Seattle (WA): University of Washington, Seattle; 1993-2018</ref>
=== Kartagener syndrome ===
Approximately 50% of patients with PCD have a subset of the condition known as [[Kartagener syndrome]], characterized by the clinical triad of:
* Primary ciliary dyskinesia
* [[Situs inversus]] (mirror-image reversal of internal organs)
* Chronic sinusitis
{| class="wikitable"
== Genetics ==
|-
PCD is inherited in an [[autosomal recessive]] manner, requiring two copies of the defective gene—one from each parent. Numerous genes have been implicated, including DNAI1, DNAH5, and others involved in the structure and function of ciliary [[dynein]] arms and associated proteins.
! Type
! [[OMIM]]
! Gene
! Locus
|-
| CILD1
| {{OMIM|244400||none}}
| [[DNAI1]]
| 9p21-p13
|-
| CILD2
| {{OMIM|606763||none}}
| ?
| 19q13.3-qter
|-
| CILD3
| {{OMIM|608644||none}}
| [[DNAH5]]
| 5p
|-
| CILD4
| {{OMIM|608646||none}}
| ?
| 15q13
|-
| CILD5
| {{OMIM|608647||none}}
| ?
| 16p12
|-
| CILD6
| {{OMIM|610852||none}}
| [[TXNDC3]]
| 7p14-p13
|-
| CILD7
| {{OMIM|611884||none}}
| [[DNAH11]]
| 7p21
|-
| CILD8
| {{OMIM|612274||none}}
| ?
| 15q24-q25
|-
| CILD9
| {{OMIM|612444||none}}
| [[DNAI2]]
| 17q25
|-
| CILD10
| {{OMIM|612518||none}}
| [[C14orf104|KTU]]
| 14q21.3
|-
| CILD11
| {{OMIM|612649||none}}
| [[RSPH4A]]
| 6q22
|-
| CILD12
| {{OMIM|612650||none}}
| [[RSPH9]]
| 6p21
|-
| CILD13
| {{OMIM|613190||none}}
| [[LRRC50]]
| 16q24.1
|}
Another gene associated with this condition is [[GAS2L2]].<ref name=Bustamante-Marin2019>{{cite journal |doi=10.1016/j.ajhg.2018.12.009 |pmid=30665704 |pmc=6372263 |title=Lack of GAS2L2 Causes PCD by Impairing Cilia Orientation and Mucociliary Clearance |journal=The American Journal of Human Genetics |volume=104 |issue=2 |pages=229–245 |year=2019 |last1=Bustamante-Marin |first1=Ximena M. |last2=Yin |first2=Wei-Ning |last3=Sears |first3=Patrick R. |last4=Werner |first4=Michael E. |last5=Brotslaw |first5=Eva J. |last6=Mitchell |first6=Brian J. |last7=Jania |first7=Corey M. |last8=Zeman |first8=Kirby L. |last9=Rogers |first9=Troy D. |last10=Herring |first10=Laura E. |last11=Refabért |first11=Luc |last12=Thomas |first12=Lucie |last13=Amselem |first13=Serge |last14=Escudier |first14=Estelle |last15=Legendre |first15=Marie |last16=Grubb |first16=Barbara R. |last17=Knowles |first17=Michael R. |last18=Zariwala |first18=Maimoona A. |last19=Ostrowski |first19=Lawrence E. }}</ref>
== Diagnosis ==
Diagnosing PCD can be challenging due to overlapping symptoms with other respiratory conditions such as [[asthma]], [[bronchiectasis]], and [[cystic fibrosis]]. Diagnostic methods include:
==Pathophysiology==
* '''Clinical evaluation''': Chronic respiratory symptoms starting early in childhood.
[[Image:Primary ciliary dyskinesia 7.jpg|thumb|left|150 px|CT image showing [[situs inversus]]. The liver is normally on the right side of the body and the spleen on the left, they are switched in this patient with situs inversus.]]
* '''[[Nasal nitric oxide]] testing''': Levels typically very low in patients with PCD.
This condition is genetically inherited. Structures that make up the cilia, including inner and/or outer [[dynein]] arms, central apparatus, radial spokes, etc. are missing or dysfunctional and thus the [[axoneme]] structure lacks the ability to move. [[Axoneme]]s are the elongated structures that make up [[cilia]] and [[flagella]]. Additionally, there may be chemical defects that interfere with ciliary function in the presence of adequate structure. Whatever the underlying cause, dysfunction of the cilia begins during and impacts the [[Human embryogenesis|embryologic phase]] of development.
* '''Genetic testing''': Identifies specific genetic mutations associated with PCD.
[[Image:Primary ciliary dyskinesia-10.jpg|thumb|Axial CT image showing dextrocardia with the IVC and morphologic right ventricle on the left and the left ventricle on the right.]]
* '''High-speed videomicroscopy''': Examination of ciliary beat frequency and coordination from nasal or bronchial biopsy samples.
* '''Electron microscopy''': Detects structural abnormalities in cilia.
* '''Imaging''': [[Chest X-ray]] and [[Computed tomography|CT scans]] may demonstrate characteristic findings like bronchiectasis or mucus plugging.
Specialised monocilia are at the heart of this problem. They lack the central-pair microtubules of ordinary motile cilia and so rotate clockwise rather than beat; in the [[primitive knot]] at the anterior end of the [[primitive streak]] in the embryo, these are angled posteriorly<ref name=pmid15118088>{{cite journal |doi=10.1073/pnas.0402001101 |pmid=15118088 |pmc=409902 |title=Fluid-dynamical basis of the embryonic development of left-right asymmetry in vertebrates |journal=Proceedings of the National Academy of Sciences |volume=101 |issue=19 |pages=7234–9 |year=2004 |last1=Cartwright |first1=J. H. E |last2=Piro |first2=O |last3=Tuval |first3=I |bibcode=2004PNAS..101.7234C }}</ref><ref name=pmid16035921>{{cite journal |doi=10.1371/journal.pbio.0030268 |pmid=16035921 |pmc=1180513 |title=De Novo Formation of Left–Right Asymmetry by Posterior Tilt of Nodal Cilia |journal=PLOS Biology |volume=3 |issue=8 |pages=e268 |year=2005 |last1=Nonaka |first1=Shigenori |last2=Yoshiba |first2=Satoko |last3=Watanabe |first3=Daisuke |last4=Ikeuchi |first4=Shingo |last5=Goto |first5=Tomonobu |last6=Marshall |first6=Wallace F |last7=Hamada |first7=Hiroshi }}</ref> such that they describe a D-shape rather than a circle.<ref name=pmid16035921/> This has been shown to generate a net leftward flow in mouse and chick embryos, and sweeps the [[protein]] to the left, triggering normal asymmetrical development.
However, in some individuals with PCD, mutations thought to be in the gene coding for the key structural protein left-right [[dynein]] (''lrd'')<ref name=pmid15222957/> result in monocilia which do not rotate. There is therefore no flow generated in the node, ''[[Sonic hedgehog|Shh]]'' moves at random within it, and 50% of those affected develop [[situs inversus]], which can occur with or without [[dextrocardia]], where the laterality of the [[viscera|internal organs]] is the mirror-image of normal. Affected individuals therefore have Kartagener syndrome. This is not the case with some PCD-related genetic mutations: at least 6%{{Citation needed|date=July 2008}} of the PCD population have a condition called [[situs ambiguus]] or heterotaxy, where organ placement or development is neither typical ([[situs solitus]]) nor totally reversed ([[situs inversus totalis]]) but is a hybrid of the two. Splenic abnormalities such as [[polysplenia]], [[asplenia]] and complex congenital heart defects are more common in individuals with situs ambiguus and PCD, as they are in all individuals with situs ambiguus.<ref name=pmid17515466>{{cite journal |doi=10.1161/CIRCULATIONAHA.106.649038 |pmid=17515466 |title=Congenital Heart Disease and Other Heterotaxic Defects in a Large Cohort of Patients with Primary Ciliary Dyskinesia |journal=Circulation |volume=115 |issue=22 |pages=2814–21 |year=2007 |last1=Kennedy |first1=M. P |last2=Omran |first2=H |last3=Leigh |first3=M. W |last4=Dell |first4=S |last5=Morgan |first5=L |last6=Molina |first6=P. L |last7=Robinson |first7=B. V |last8=Minnix |first8=S. L |last9=Olbrich |first9=H |last10=Severin |first10=T |last11=Ahrens |first11=P |last12=Lange |first12=L |last13=Morillas |first13=H. N |last14=Noone |first14=P. G |last15=Zariwala |first15=M. A |last16=Knowles |first16=M. R |doi-access=free }}</ref>
== Management and treatment ==
PCD has no cure, but management focuses on preventing complications and reducing symptom severity:
The genetic forces linking failure of nodal monocilia and situs issues and the relationship of those forces to PCD are the subject of intense research interest. However, knowledge in this area is constantly advancing.
=== Chest physiotherapy ===
Daily airway clearance techniques help remove mucus, reducing infection frequency and preserving lung function:
* Postural drainage
* Chest percussion and vibration
* Active breathing techniques
* Use of mechanical mucus clearance devices
=== Relation to other rare genetic disorders ===
=== Medication ===
Recent findings in genetic research have suggested that a large number of [[genetic disorder]]s, both [[Syndrome|genetic syndromes]] and [[Disease|genetic diseases]], that were not previously identified in the medical literature as related, may be, in fact, highly related in the [[genotype|genetypical]] root cause of the widely varying, [[phenotype|phenotypically]]-observed [[Disorder (medicine)|disorders]]. Thus, PCD is a [[ciliopathy]]. Other known ciliopathies include [[Bardet–Biedl syndrome]], [[polycystic kidney disease|polycystic kidney]] and [[polycystic liver disease|liver disease]], [[nephronophthisis]], [[Alström syndrome]], [[Meckel–Gruber syndrome]] and some forms of [[Retinopathy|retinal degeneration]].<ref name=pmid16722803>{{cite journal |doi=10.1146/annurev.genom.7.080505.115610 |pmid=16722803 |title=The Ciliopathies: An Emerging Class of Human Genetic Disorders |journal=Annual Review of Genomics and Human Genetics |volume=7 |pages=125–48 |year=2006 |last1=Badano |first1=Jose L |last2=Mitsuma |first2=Norimasa |last3=Beales |first3=Phil L |last4=Katsanis |first4=Nicholas }}</ref>
Pharmacologic management includes:
* Antibiotics for frequent respiratory infections, including prophylactic or intermittent courses.
* Mucolytics to decrease mucus viscosity (e.g., hypertonic saline inhalation).
* Bronchodilators, if airway hyperreactivity is present.
* Placement of ventilation tubes in cases of chronic ear infections.
Several diagnostic tests for this condition have been proposed.<ref name=pmid28790179>{{cite journal |doi=10.1136/thoraxjnl-2017-209999 |pmid=28790179 |pmc=5771957 |title=High prevalence ofCCDC103p.His154Pro mutation causing primary ciliary dyskinesia disrupts protein oligomerisation and is associated with normal diagnostic investigations |journal=Thorax |volume=73 |issue=2 |pages=157–166 |year=2018 |last1=Shoemark |first1=Amelia |last2=Moya |first2=Eduardo |last3=Hirst |first3=Robert A |last4=Patel |first4=Mitali P |last5=Robson |first5=Evelyn A |last6=Hayward |first6=Jane |last7=Scully |first7=Juliet |last8=Fassad |first8=Mahmoud R |last9=Lamb |first9=William |last10=Schmidts |first10=Miriam |last11=Dixon |first11=Mellisa |last12=Patel-King |first12=Ramila S |last13=Rogers |first13=Andrew V |last14=Rutman |first14=Andrew |last15=Jackson |first15=Claire L |last16=Goggin |first16=Patricia |last17=Rubbo |first17=Bruna |last18=Ollosson |first18=Sarah |last19=Carr |first19=Siobhán |last20=Walker |first20=Woolf |last21=Adler |first21=Beryl |last22=Loebinger |first22=Michael R |last23=Wilson |first23=Robert |last24=Bush |first24=Andrew |last25=Williams |first25=Hywel |last26=Boustred |first26=Christopher |last27=Jenkins |first27=Lucy |last28=Sheridan |first28=Eamonn |last29=Chung |first29=Eddie M K |last30=Watson |first30=Christopher M |display-authors=29 }}</ref> These include nasal [[nitric oxide]] levels as a screening test, light microscopy of biopsies for ciliary beat pattern and frequency and electron microscopic examination of [[dynein]] arms, as the definite diagnosis method. Genetic testing has also been proposed but this is difficult given that there are multiple genes involved.
=== Fertility assistance ===
Patients experiencing infertility may benefit from assisted reproductive techniques such as [[in vitro fertilization]] (IVF).
===Classification===
== Prognosis ==
PCD is a chronic, lifelong condition. Early diagnosis and aggressive management of infections and airway clearance can significantly improve quality of life and slow disease progression. Without appropriate management, PCD can result in severe lung damage and reduced lifespan.
[[Image:Primary ciliary dyskinesia-8.jpg|thumb|Axial CT image showing chronic sinusitis in an individual with Kartagener syndrome.]]
== Epidemiology ==
When accompanied by the combination of [[situs inversus]] (reversal of the internal organs), [[chronic sinusitis]], and [[bronchiectasis]], it is known as Kartagener syndrome (only 50% of primary ciliary dyskinesia cases include situs inversus).
Primary ciliary dyskinesia is rare, affecting approximately 1 in 10,000 to 1 in 20,000 births globally. Prevalence may be higher in populations with increased consanguinity.
==Treatment==
== Research ==
There are no standardized effective treatment strategies for the condition. Current therapies for PCD are extrapolated from Cystic Fibrosis and patients with non-CF bronchiectasis and lack validation for PCD-specific use.<ref>{{cite journal |last1=Knowles |first1=Michael |last2=Daniels |first2=Leigh Anne |last3=Davis |first3=Stephanie |last4=Zariwala |first4=Maimoona |last5=Leigh |first5=Margaret |title=Primary Ciliary Dyskinesia. Recent Advances in Diagnostics, Genetics, and Characterization of Clinical Disease |journal=American Journal of Respiratory and Critical Care Medicine |date=June 24, 2013 |volume=188 |issue=8 |pages=913–22 |doi=10.1164/rccm.201301-0059CI |pmid=23796196 |pmc=3826280 }}</ref> Severe fatal respiratory failure can develop; long-term treatment with macrolides such as [[clarithromycin]], [[erythromycin]] and [[azithromycin]] has been empirically applied for the treatment of primary ciliary dyskinesia in Japan, though controversial due to the effects of the medications.<ref name=pmid22576394>{{cite journal |doi=10.2169/internalmedicine.51.6617 |pmid=22576394 |title=Two Cases of Primary Ciliary Dyskinesia with Different Responses to Macrolide Treatment |journal=Internal Medicine |volume=51 |issue=9 |pages=1093–8 |year=2012 |last1=Kido |first1=Takashi |last2=Yatera |first2=Kazuhiro |last3=Yamasaki |first3=Kei |last4=Nagata |first4=Shuya |last5=Choujin |first5=Yasuo |last6=Yamaga |first6=Chiyo |last7=Hara |first7=Kanako |last8=Ishimoto |first8=Hiroshi |last9=Hisaoka |first9=Masanori |last10=Mukae |first10=Hiroshi |doi-access=free }}</ref>
Research continues to explore gene-specific therapies and advanced diagnostic techniques to improve outcomes and quality of life for individuals with PCD. Studies on nitric oxide pathways and ciliary biology provide insights into novel therapeutic approaches.
== Prognosis ==
== Gallery ==
There is no reliable estimate of life expectancy for people with PCD.<ref>{{cite web |title=FREQUENTLY ASKED QUESTIONS Everything you need to know about primary ciliary dyskinesia (PCD)! |url=https://pcdfoundation.org/faq/ |website=PCD Foundation |accessdate=16 September 2018}}</ref> The largest multi-center study of lung function in people with PCD across many European countries found strong evidence refuting a common assumption that it is a mild disease. This study found that lung function of people with PCD is comparable to those with cystic fibrosis in childhood but is better in young adulthood.<ref>{{cite journal |last1=Halbeisen |first1=Floran |last2=Goutaki |first2=Myrofora |last3=Spycher |first3=Ben |last4=Amirav |first4=Israel |last5=Laura |first5=Behan |last6=Boon |first6=Mieke |last7=Hogg |first7=Claire |last8=Casa |first8=Carmen |last9=Crowl |first9=Suzanne |last10=Haarman |first10=Eric |last11=Bulent |first11=Karadag |title=Lung function in patients with primary ciliary dyskinesia: an iPCD Cohort study |journal=The European Respiratory Journal |date=August 2018 |volume=52 |issue=2 |pages=1801040 |doi=10.1183/13993003.01040-2018 |pmid=30049738 |doi-access=free }}</ref> Both diseases, however, are progressive and lung function declines with age relative to peer groups.
<gallery>
Survey data indicate that respiratory symptoms increase progressively and continuously beginning in the mid-20s relative to the population norm.<ref>{{cite journal |doi=10.1186/1471-2466-3-4 |pmid=14641928 |pmc=317322 |title=Primary ciliary dyskinesia (Siewert's / Kartagener's Syndrome): Respiratory symptoms and psycho-social impact |journal=BMC Pulmonary Medicine |volume=3 |pages=4 |year=2003 |last1=McManus |first1=I Christopher |last2=Mitchison |first2=Hannah M. |last3=Chung |first3=Eddie MK |last4=Stubbings |first4=Georgina F. |last5=Martin |first5=Naomi }}</ref>
File:Primary ciliary dyskinesia-1.jpg|Bronchiectasis associated with Kartagener syndrome
File:Primary ciliary dyskinesia-6.jpg|Cylindrical bronchiectasis in lower lobes
</gallery>
==History==
== See also ==
The classic symptom combination associated with PCD was first described by A. K. Zivert<ref>{{cite journal |author=Zivert AK |title=Über einen Fall von Bronchiectasie bei einem Patienten mit situs inversus viscerum |trans-title=About a case of bronchiectasis in a patient avec situs inversus viscerum |language=de |journal=Berliner Klinische Wochenschrift |year=1904 |volume=41 |pages=139–141 }}</ref> in 1904, while Kartagener published his first report on the subject in 1933.<ref>{{cite journal |doi=10.1007/BF02141468 |title=Zur Pathogenese der Bronchiektasien |trans-title=The pathogenesis of bronchiectasis |language=de |journal=Beiträge zur Klinik der Tuberkulose und Spezifischen Tuberkulose-Forschung |volume=83 |issue=4 |pages=489–501 |year=1933 |last1=Kartagener |first1=M |s2cid=7708592 }}</ref>
* [[Kartagener syndrome]]
* [[Bronchiectasis]]
* [[Ciliopathy]]
* [[Situs inversus]]
==References==
{{Reflist}}
==Further reading==
*[https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=pcd GeneReview/NCBI/NIH/UW entry on Primary Ciliary Dyskinesia]
* [https://rarediseases.info.nih.gov/diseases/744/primary-ciliary-dyskinesia Genetic and Rare Diseases Information Center (GARD)]
| ICD10 = {{ICD10|J|98|0|q|80}}*
| ICD9 = {{ICD9|759.3}}*
| ICDO =
| OMIM = 244400
| OMIM_mult = {{OMIM|242650||none}}
| MedlinePlus =
| eMedicineSubj = med
| eMedicineTopic = 1220
| eMedicine_mult = {{eMedicine2|ped|1166}}
| MeshID = D002925
}}
''This article may contain some text from the public domain source "National Heart, Lung, and Blood Institute Rare Diseases Report FY 2001" available at'' https://web.archive.org/web/20041017103349/http://nhlbi.nih.gov/resources/docs/raredisrpt01.htm
{{Other genetic disorders by mechanism}}
{{Other genetic disorders by mechanism}}
[[Category:Autosomal recessive disorders]]
[[Category:Autosomal recessive disorders]]
[[Category:Respiratory diseases]]
[[Category:Respiratory diseases]]
Revision as of 02:12, 30 March 2025
Rare autosomal recessive genetic disorder affecting ciliary function
Chest physiotherapy, antibiotics, supportive care, surgical interventions
Medication
Antibiotics, mucolytics
Prognosis
Variable; good management can improve quality of life
Frequency
Approximately 1 in 10,000 to 1 in 20,000 births
Deaths
N/A
Primary ciliary dyskinesia (PCD) is a rare, ciliopathicautosomal recessivegenetic disorder characterized by abnormal function of cilia, the microscopic hair-like structures lining various organs such as the respiratory tract, sinuses, Eustachian tube, middle ear, and reproductive organs. Historically termed "immotile cilia syndrome," the term is no longer preferred, as the cilia retain movement, although their action is typically inefficient or unsynchronized.
Pathophysiology
PCD is caused by genetic mutations that affect the structure and function of motile cilia. Normally, these cilia beat synchronously 7 to 22 times per second, facilitating mucus clearance through the mucociliary escalator. Dysfunctional cilia result in impaired mucus clearance, causing recurrent infections and chronic inflammation.
Signs and symptoms
CT scan demonstrating bronchiectasis in PCD (Kartagener syndrome)Sagittal CT showing cylindrical bronchiectasis in lower lung lobes in PCD patient
The primary symptoms of PCD result from impaired mucus clearance and chronic respiratory infections. Symptoms usually begin early in childhood and can include:
Progressive development of bronchiectasis—permanent dilation and damage to the airways
Reduced lung function over time
Non-respiratory symptoms include:
Infertility due to impaired ciliary function in the reproductive tract:
Male infertility related to immotile sperm flagella
Female infertility or increased risk of ectopic pregnancy due to impaired cilia in the fallopian tubes
Kartagener syndrome
Approximately 50% of patients with PCD have a subset of the condition known as Kartagener syndrome, characterized by the clinical triad of:
Primary ciliary dyskinesia
Situs inversus (mirror-image reversal of internal organs)
Chronic sinusitis
Genetics
PCD is inherited in an autosomal recessive manner, requiring two copies of the defective gene—one from each parent. Numerous genes have been implicated, including DNAI1, DNAH5, and others involved in the structure and function of ciliary dynein arms and associated proteins.
Diagnosis
Diagnosing PCD can be challenging due to overlapping symptoms with other respiratory conditions such as asthma, bronchiectasis, and cystic fibrosis. Diagnostic methods include:
Clinical evaluation: Chronic respiratory symptoms starting early in childhood.
Nasal nitric oxide testing: Levels typically very low in patients with PCD.
Genetic testing: Identifies specific genetic mutations associated with PCD.
High-speed videomicroscopy: Examination of ciliary beat frequency and coordination from nasal or bronchial biopsy samples.
Electron microscopy: Detects structural abnormalities in cilia.
Imaging: Chest X-ray and CT scans may demonstrate characteristic findings like bronchiectasis or mucus plugging.
Placement of ventilation tubes in cases of chronic ear infections.
Fertility assistance
Patients experiencing infertility may benefit from assisted reproductive techniques such as in vitro fertilization (IVF).
Prognosis
PCD is a chronic, lifelong condition. Early diagnosis and aggressive management of infections and airway clearance can significantly improve quality of life and slow disease progression. Without appropriate management, PCD can result in severe lung damage and reduced lifespan.
Epidemiology
Primary ciliary dyskinesia is rare, affecting approximately 1 in 10,000 to 1 in 20,000 births globally. Prevalence may be higher in populations with increased consanguinity.
Research
Research continues to explore gene-specific therapies and advanced diagnostic techniques to improve outcomes and quality of life for individuals with PCD. Studies on nitric oxide pathways and ciliary biology provide insights into novel therapeutic approaches.
Gallery
CT scan showing mucus impaction ("tree-in-bud")
Bronchiectasis associated with Kartagener syndrome
CT scan showing mucus impaction ("tree-in-bud")
Bronchiectasis associated with Kartagener syndrome
Cylindrical bronchiectasis in lower lobes
