2. Primary Ciliary Dyskinesia:
Missing a Beat: Primary Ciliary Dyskinesia
Impaired Airway Clearance and
Respiratory Disease
Michele Manion, Executive Director
PCD Foundation
www.pcdfoundation.org
4. What is Primary Ciliary
Dyskinesia (PCD)?
Umbrella term for genetic disorders affecting proteins
responsible for the structure and/or function of motile
(moving) cilia. Also called immotile cilia syndrome,
Kartagener syndrome (PCD with situs inversus)
One of three recognized genetic disorders of
mucociliary clearance (along with cystic fibrosis and
pseudohypoaldosteronism) currently being studied in a
North American research consortium
5. PCD: The Historical Perspective
(or What’s With all the Names?)
•1904 AW Siewert makes first mention of a triad of
bronchiectasis, dextrocardia and sinusitis/nasal polyps
•1933 Manes Kartagener (Swiss pediatrician) published a report
of 4 children with bronchiectasis, sinusitis and situs inversus.
The syndrome is named “Kartagener Syndrome.”
•1975 Afzelius (Swedish ultrastructuralist) and Pedersen
(Denmark) independently hypothesize that “immotile cilia” may
be the underlying cause and the syndrome is renamed
“immotile cilia syndrome.” Both names (Kartagener & ICS
persist).
•1981 Based on new understanding of cilia pathogenesis, Sleigh
suggests a name change to “primary ciliary dyskinesia”
6. PCD Demographics
PCD Prevalence: Range from 1:4,100* to 1:15,000**
Estimated PCDF Database
US: 20,773 – 74,880 426
SC 312 – 1,411 6
*Katsuhara K, Kawamoto S, Wakabayashi T, et al. Situs inversus totalis and
Kartagener’s syndrome in a Japanese population. Chest 1972; 61: 56–61.
**Afzelius BA, Stenram U. Prevalence and genetics of immotile-cilia syndrome and left-
handedness. Int J Dev Biol 2006; 50: 571–573 .
7. What are Cilia?
Three Types of Cilia in Human Cells:
Motile (respiratory epithelium, organs of
reproduction, ependymal
lining of ventricles of brain, etc.)
Nodal (specialized organelle appearing once
only on the embryonic node)
Primary (non-motile chemosensory monocilia)
8. What are Cilia?
Cilia and flagella are microtubule-based
organelles that extend from the surface of
almost all cell types in the human body
Ciliated Respiratory Epithelium Nodal (Primary) Monocilia
Courtesy Johnny Carson, PhD Courtesy Fliegauf M, et al Nat Rev Mol Cell Biol. Nov 2007
9. What are Cilia?
Cross-section
of typical
“9+0” sensory
cilium
Ainesworth, C. NATURE Vol 448:9, August 2007
10. What are Cilia?
Cross-section
of typical
“9+2” motile
cilium
Ainesworth, C. NATURE, Vol 448:9 August 2007
11. What are Cilia?
700-750 genes
in the ciliary
structure
including the
basal body
12. What are Cilia?
The Role of Non-Motile Cilia in Cells
Once thought to be vestigial leftovers from
evolution
Importance only discovered in last decade
Provide crucial sensory functions to the cells
Now implicated in a number of human
diseases, including PKD, spina bifida, bone &
connective tissue disorders, retinal disorders
and a host of pleiotropic diseases (Bardet-Biedl,
Alstrom, Meckel’s, Joubert, Juene’s, etc.)
Focus of intense research, due to connection
between primary cilia and obesity.
Bush A, Hogg C. Primary ciliary dyskinesia: recent advances in epidemiology, diagnosis, management
and relationship with the expanding spectrum of ciliopathy. Expert Rev Respir Med. 2012 Dec;6(6):663-
82. doi: 10.1586/ers.12.60. PubMed PMID: 23234452.
13. What are Cilia?
Cilia vs. Flagella
Ciliated Respiratory Epithelium Flagellated Chlamydomonas
Courtesy David Howard: http://www.uwlax.edu/biology/faculty/Howard/Research.htm
14. What Are Cilia?
Where are Motile Cilia Found?
Upper & lower respiratory tract
Eustachian tube of middle ear
Ependymal lining of the ventricles of the brain
Fallopian tubes of the female reproductive
system
Sperm tails (technically flagella, but
structurally similar to cilia)
15. What are Cilia?
Cilia in the Respiratory Tract
•Ciliated cells account for approximately 80% of the cells lining surface
of the conducting airways.
•Ciliated cells in coordination with secretory cells represent a first line
of defense for the respiratory tract against potential pathogens/
particulate matter in the inspired air.
•Respiratory epithelial cells each have about 200-300 cilia that beat in a
coordinated “metachronal” wave.
•Effective ‘wave’ or beat facilitated by slippery glycoprotein coating on
individual cilium
Button B, et al A periciliary brush promotes the lung health by separating the mucus layer from airway
epithelia. Science. 2012 Aug 24;337(6097):937-41. doi: 10.1126/science.1223012. PubMed PMID: 2
16. How Do Motile Cilia Work?
Microtubular pair
Outer dynein arms
Microtubular pair
Cilia graphics courtesy Johnny Carson, PhD, UNC, Chapel Hill
19. How Do Motile Cilia Work?
How Important is ATP?
Cilia from bovine trachea in Add a little ATP and… Voilà
Petri dish
Cilia graphics courtesy Johnny Carson, PhD, UNC, Chapel Hill
20. How Do Motile Cilia Work?
Normal
Ciliary
Activity
(Real Time)
Courtesy of John C. Carson, PhD, University of North Carolina at Chapel Hill
21. How Do Motile Cilia Work?
Normal
Ciliary
Activity
(Real Time)
Courtesy John C. Carson, PhD, University of North Carolina at Chapel Hill
22. How Do Motile Cilia Work?
Normal
Ciliary
Activity
Courtesy John C. Carson, PhD, University of North Carolina at Chapel Hill
23. How Do Motile Cilia Work?
Metachronal, synchronized ‘wave’ of ciliated epithelium
Normal
Ciliary
Activity
Courtesy of John C. Carson, PhD, University of North Carolina at Chapel Hill
24. How Do Motile Cilia Work?
Normal
Ciliary
Activity
Courtesy Robert E. Wood, MD, PhD, University of Cincinnati
27. What Happens in PCD?
PCD
Ciliary
Activity
(Real Time)
Courtesy John C. Carson, PhD, University of North Carolina at Chapel Hill
28. What Happens in PCD?
PCD Ciliary Activity
(Real Time)
Courtesy John C. Carson, PhD, University of North Carolina at Chapel Hill
29. What Happens in PCD?
Ciliary
Activity:
Side by Side
Comparison
(Real Time)
Courtesy John C. Carson, PhD, University of North Carolina at Chapel Hill
30. PCD: Clinical Consequences
What are the Clinical Consequences of
PCD?
Consequences begin before birth
Specialized “nodal” cilia on the embryonic
node are unique—9+0 cilia WITH dynein arms
Nodal cilia “twirl” rather than beat
31. PCD: Clinical Consequences
‘9 + 0’ Nodal Cilium
Courtesy John C. Carson, PhD, University of North Carolina at Chapel Hill
33. PCD: Clinical Consequences
Nodal cilia and left-right asymmetry
The absence of nodal ciliary motion results in
random organ placement, including laterality
defects (also called heterotaxy):
Situs solitus (typical organ placement)
Situs inversus totalis (complete mirror-image
organ placement)
Situs ambiguus or ambiguous (any placement
other than situs solitus or situs inversus)
Hirokawa et al. Cell 125:33-45, 2006
34. PCD: Clinical Consequences
Ciliary Dysfunction and Laterality Defects
Fliegauf M, Benzing T, Omran H. Nat Rev Mol Cell Biol. 2007 Nov;8(11):880-93
35. PCD: Clinical Consequences
Ciliary Dysfunction and Laterality Defects
Without ciliary activity, organ placement (situs) is random
Situs solitus (normal) Situs inversus totalis
L
H
H
L S
S L
Monozygotic Twins with PCD
Noone et al., Am J Med Genet. 1999 Jan 15;82(2):155-60
37. PCD: Clinical Consequences
PCD Patients Situs Status in PCD Patients
n=337
Situs Solitus Heterotaxy Situs Inversus
n=155 (46%) n=21 (6.3%) Totalis
N=161 (47.7%)
Complex Congenital No cardiac or
Vascular
Heart Disease vascular anomalies
Anomalies
n=8 (2.4%) n=9 (2.7%)
n=4 (1.2%)
Kennedy, et al., Circulation. 2007 Jun 5;115(22):2814-21
38. PCD: Clinical Consequences
PCD, Heterotaxy and CHD
At least 13% (current data suggests 18-20) of patients with PCD had heterotaxy,
which was usually associated with defective ODAs and more frequently
mutations in DNAI1 and DNAH5
Many PCD patients with heterotaxy had cardiac and/or vascular anomalies
(12/21), and most (8/12) had complex CHD that required surgery
The prevalence of CHD related to heterotaxy is 200-fold higher
in PCD than in the general population (1:50 vs. 1:10,000)
Conclusions
1. Patients with PCD should have formal cardiac evaluation
2. Genetic mutations that adversely affect respiratory and
embryological nodal cilia cause heterotaxy and CHD, and patients
with these conditions should be evaluated for cardiac defects
Kennedy, et al., Circulation. 2007 Jun 5;115(22):2814-21
39. PCD: Clinical Consequences
PCD, Heterotaxy and CHD
Pilot study at National Children’s Medical Center: Data From
American Thoracic Society Symposium, May, 2009:
Evaluated 26 children referred for CHD/heterotaxy surgical repairs
Diagnostic workup included EM’s, nasal NO and compatible clinical
history (chronic upper and lower respiratory infection)
Results:
50% of these children were determined to have probable PCD (7 with
a confirmed phenotype and 6 with low nasal NO and ciliary
dysmotility, but no observable beat defect).
N. Nakhleh; Data presented at ATS 2009
40. PCD: Clinical Consequences
PCD, Heterotaxy and CHD
NHLBI Study on Dyskinesia, Heterotaxy and
Congenital Heart Disease (NCT00608556)
Currently recruiting
325 Patients
Ages 2 & above
Patients with heterotaxy, situs inversus or CHD
Patients with PCD
41. PCD: Clinical Consequences
PCD, Heterotaxy and CHD
“Patients with heterotaxy and congenital heart disease have high mortality and
morbidity (often related to respiratory complications). Recent studies have
revealed an association among heterotaxy, congenital heart disease, and
primary ciliary dyskinesia.”
•Retrospective chart review
•87 heterotaxy patients compared to 634 procedure matched non-heterotaxy
patients
Swisher M, Jonas R, Tian X, Lee ES, Lo CW, Leatherbury L. Increased postoperative
and respiratory complications in patients with congenital heart disease associated
with heterotaxy. J Thorac Cardiovasc Surg. 2010 Sep 28.
42. PCD: Clinical Consequences
PCD, Heterotaxy and CHD
Findings: On all measures of post-surgical respiratory function, patients with
heterotaxy experienced significantly greater complications than procedure
matched non-heterotaxy patients. The authors suspect this is due to
undiagnosed ciliary dysfunction as a previously unrecognized surgical risk
factor in this group.
•Postoperative stay
•Mechanical ventilation
•Tracheostomies
•ECMO
•Death
Swisher M, Jonas R, Tian X, Lee ES, Lo CW, Leatherbury L. Increased postoperative
and respiratory complications in patients with congenital heart disease associated
with heterotaxy. J Thorac Cardiovasc Surg. 2010 Sep 28.
43. PCD: Clues to Diagnosis
Neonatal Respiratory Distress:
A Very Important Diagnostic Indicator in PCD
~85-90% of PCD term neonates have respiratory
distress thought to reflect the importance of ciliary
activity when the neonatal lung switches from a
liquid to a gas environment.
Neonatal respiratory distress in PCD can lead to infant
mortality
GDMCC Study, unpublished data
44. PCD: Clues to Diagnosis
Neonatal Respiratory Distress:
Opportunity for Early Diagnosis?
2011 HHS new recommendation for pulse oximetry
screening of neonates 24 to 48 after birth.
<95% repeat x 3
<90% immediate echo and clinical eval
GDMCC Study, unpublished data
45. PCD: Clues to Diagnosis
Neonatal Respiratory Distress: Opportunity for Early
Diagnosis?
150 Responses
84.3% “Yes”
PCD Foundation Data, 2012
46. PCD: Clues to Diagnosis
Neonatal Respiratory Distress: Opportunity for Early
Diagnosis?
55% Required
NICU Admission
PCD Foundation Data, 2012
47. PCD: Clues to Diagnosis
Neonatal Respiratory Distress: Opportunity for Early
Diagnosis?
Average SPO2 in PCD
Term Neonates Was 82%
PCD Foundation Data, 2012
48. PCD: Clues to Diagnosis
Clinical Consequences of PCD:
Early Years
Majority of PCD infants have a history of neonatal respiratory
distress.
Most report repeated infections of the ears, sinuses and lungs
in the first year of life
“Noisy chest” or “juicy kid syndrome”
Often misdiagnosed as asthma or allergies
“Right middle lobe syndrome” common early dx
Hearing loss/speech delays
49. PCD: Clues to Diagnosis
Clinical Consequences of PCD: Early Years
Increased incidence of pectus deformities
(10% vs. .3%) and scoliois/kyphoscoliosis (5-
10%) 1
Manion, M. , personal adorable baby picture collection .
1, Kennedy, et al. 2007: Circulation. 115:2814-2821
50. Clues to Dx: ENT Findings in PCD
Otitis Media Polyps
51. PCD: Clues to Diagnosis
Exhaled
Nasal Nitric
Oxide in PCD
Noone et al., Am J Med Genet. 1999 Jan 15;82(2):155-60
52. PCD: Clues to Diagnosis
Respiratory Status in PCD: Early Years
Common Bugs: Less Common Bugs:
S. aureus P. aeruginosa (smooth)
H. influenza P. aeruginosa (mucoid)--rare
S. pneumoniae Nontuberculous mycobacterium
Bronchiectasis develops early and 60% of PCD children between
the ages of 5 and 18 have HRCT evidence of bronchiectasis in
1 to 6 lobes
Leigh, et al. Pediatr Pulmonol. 2008 May;43(5):514-6
53. PCD: Clues to Diagnosis
Leigh, et al. Presentation at NACFC 2011
54. PCD: Clues to Diagnosis
Extent of Bronchiectasis by Organisms in Sputum
Leigh, et al.
55. PCD: Clues to Diagnosis
Extensive Bronchiectasis with Normal Spirometry
•10 year boy with PCD
•FEV1 90.1% predicted
•Chest CT:
Bronchiectasis in both
lower lobes, lingula and
right middle lobe
Atelectasis in right middle
lobe and lingula
Leigh, et al.
56. PCD: Clues to Diagnosis
Clinical Consequences of PCD:
Adults
Neurogenic hearing loss may occur
Fertility issues are a concern
Bug profile gets nastier: NTM infections (20%), mucoid
Pseudomonas and other gram-negatives more common.
Bronchiectasis is universal
Pulmonary functions are variable & don’t always correlate well
to actual extent of lung disease and respiratory flora present
Many patients on disability by mid-30s to early 40s
Some opt for lung transplant
57. PCD: Clues to Diagnosis
Clinical Consequences of PCD:
Adults Age Gender Situs
0 M SI
0 F SA
0 F SA
Average age at death: 0 M SA
24 F SA
44 (34.8 if infants are
24 M SS
included) 32 F SS
39 F SI
42 M SS
45 F SI
47 M SS
50 F SI
55 F SS
64 M SA
66 F SS
58. Bottom Line: PCD IS A
PROGRESSIVE DISORDER THAT
REQUIRES AGGRESSIVE
TREATMENT
59. PCD: Making the Diagnosis
Assessing Ciliary Ultrastructure
Courtesy GDMCC Slide Set
60. PCD: Clues to Diagnosis
Assessing
ciliary
ultrastructure
Leigh, M., Semin Respir Crit Care Med. 2003 Dec;24(6)
61. PCD: Clues to Diagnosis
Assessing ciliary
ultrastructure
Leigh, M., Semin Respir Crit Care Med. 2003 Dec;24(6)
62. What are Cilia?
Harwell Mouse Genetics: http://www.har.mrc.ac.uk/research/functional-genomics-
section/cilia-development-and-disease/projects
63. PCD: Clues to Diagnosis
Assessing
ciliary beat
Leigh, M., Semin Respir Crit Care Med. 2003 Dec;24(6)
64. PCD: Clues to Diagnosis
CF vs. PCD
Comparison
Leigh, M., Semin Respir Crit Care Med. 2003 Dec;24(6)
65. PCD: Clues to Diagnosis
PCD vs. CF
Courtesy Michael Knowles, MD, UNC, Chapel Hill
66. PCD: Clues to Diagnosis
Characteristic of Both PCD and CF:
Both are genetic disorders of mucociliary clearance
Both are characterized by bronchiectatic lung
disease and opportunistic pathogen infection
Lung disease in PCD generally progresses slower
than CF lung disease (preserved cough clearance?)
Characteristic of PCD, but not CF:
•Neonatal respiratory distress •Chronic rhinorrhea
•Situs anomalies •Good nutritional status
•Otitis media/hearing loss •Bronchiectasis
w/normal flora
Leigh, M., Semin Respir Crit Care Med. 2003 Dec;24(6)
68. Treatment for PCD
No therapeutic studies published in PCD
•Small, geographically dispersed patient population
•Seriously under and misdiagnosed (22-30%
misdiagnosis) calling into question published “PCD
data”
Most Centers Follow CF Treatment Guidelines:
•Aggressive tx of infections
•Aggressive airway clearance therapy
•Routine PFTs, sputum culture surveillance
69. PCD DX & TX: The Future
GDMCC (Genetic Disorders of Mucociliary
Clearance Consortium Study)
The PCDF is collaborating with UNC, Chapel Hill on a large
multi-center trial. This trial is sponsored by the Office of
Rare Diseases at the NIH. Aims of this first-ever effort to
collect data on a large cohort of PCD patients include:
•Identify patients and refine demographics
•Resolve diagnostic dilemmas
•Document natural history of the disease and identify
possible targets for therapeutic intervention
http://rarediseasesnetwork.epi.usf.edu/
70. PCD DX & TX: The Future
The GDMC: Achievements So far:
Confirmed large cohort (400+ patients) to participate in clinical trials
Produced first diagnostic genetic test for PCD (picks up ~35% of all
cases of PCD and ~65% of PCD related to ODA defects)
Established connection between PCD, heterotaxy and CHD
Validated perceived problem with misdiagnosis
Identified previously unrecognized severity of lung disease in PCD
infants and young children
Identified areas of overlap between PCD and other ciliopathies
Discovered PCD outer dynein arm mutations (DNAH11) that has no
identifiable ultrastructural correlate and normal appearing beat
http://rarediseasesnetwork.epi.usf.edu/
71. PCD: Better Options for Dx
Phenotype + nNO
Four clinical features + nNO= 98% accuracy in one study
Genetics
18 PCD genes confirmed and published
14 on commercially available tests
8 (at least) known to be in process of validation
Potential for Neonatal Diagnosis with Newborn Screening for
CCHD
Leigh, M., Semin Respir Crit Care Med. 2003 Dec;24(6)
72. PCD DX & TX: The Future
Eight PCD Research Network & “Centers of Excellence”
University of North Carolina, Chapel Hill, NC
(Michael Knowles, MD & Margaret Leigh, MD)
NIAID, NIH, Bethesda, MD (Ken Olivier, MD)
Washington University, St. Louis, MO (Thomas Ferkol, MD)
The Children’s Hospital, Denver, CO (Scott Sagel, MD)
Stanford University, Stanford, CA (Carlos Milla, MD)
University of Washington, Seattle, WA (Margaret Rosenfeld, MD)
The Hospital for Sick Children, Toronto (Sharon Dell, MD)
Indiana Children’s Hospital (Stephanie Davis, MD)
http://rarediseasesnetwork.epi.usf.edu/
73. Path to Clinical Trials
The Path to Clinical Trials (PTCT)
Two mission critical building blocks:
-Network of PCD Expert Centers
-Patient Registry
74. Path to Clinical Trials
Four PCD Clinical & Research Centers
•Boston Children’s Hospital (Dr. Umakanth Khatwa)
•University of Chicago (Dr. Pamela McShane)
•Children’s Hospital of Philadelphia (Dr. Samuel Golfarb/Dr. Maureen Josephson
•Rainbow Babies Hospital (Dr. Benjamin Gaston)
Nine PCD Affiliate Center
•University of South Carolina (Dr. Trey Brown)
•University of Miami (Dr. Andrew Colin)
•Children's Los Angeles (Dr. Sally Ward)
•University of Tennessee (Dr. Dennis Stokes)
•University of Tampa (Dr. Marisa Couluris)
•University of Wisconsin (Dr. Diana Quintero)
•Children’s Hospital of Eastern Ontario (Dr. Tom Kovesi)
•McGill University Montreal, Quebec (Dr. Adam Shapiro)
•Respiratory Associates Nova Scotia (Dr. Dimas Mateos-Corral
http://www.pcdfoundation.org/en/finding-a-cure/path-to-clinical-trials
75. Path to Clinical Trials
Global Rare Diseases Registry
http://www.pcdfoundation.org/en/finding-a-cure/path-to-clinical-trials
76. PCD: Priorities for the Future
• Whole Exome/Genome Sequencing
Pilot project in Seattle
• Small Molecule Compounds
Success in laboratory setting
77. Making the Diagnosis of PCD:
Why Does it Matter?
• Very few people have PCD, but we all have cilia
• The emerging field of ciliopathies demonstrates the
importance of understanding ciliary genetics and
disease function
• We are all only one conception away from discovering
we carry a recessive trait like PCD.
78. PCD DX & TX: The Future
Classic PCD
Atypical disease
Predisposition to disease
Courtesy Michael Knowles, MD, University of North Carolina, Chapel Hill
79. Thank you Sponsors, Electromed,
PCD Research Group
Contact Information: Michele Manion
PCD Foundation
info@pcdfoundation.org
www.pcdfoundation.org
952-303-3155
Kartagener ultimately reviewed hundreds of cases—all pediatric—so he never made the connection with infertility, which is what triggered Afzelius’s eventual “light bulb” that cilia might be the common factor explaining both Siewert and Kartagener’s findings. There was a flurry of interest and many publications between 1975 and 1980. Further investigation demonstrated that the cilia were not truly immotile, but had dsykinetic motility. Iren 1981, Sleigh recommended renaming the syndrome “primary ciliary dyskinesia” to reflect both the genetic nature of the disorder and more accurately reflect the reality of the motility disorder.
Estimates vary wildly. ‘Classic’ PCD is likely to affect 1:12-15,000. One contributing factor to the difficulty in diagnosing people with PCD is nomenclature. There is no known gender or race bias in PCD although small communities where inter-marriage is practiced tend to have a higher rate (Amish, East Indian, Native American, Ashkenazic Jews).
There are three main types of cilia, distinguished by their ultrastructure. ed on motility and the presence or absence of a central pair of microtubules. Sensory cilia (also called primary or monocilia) are almost always 9+0 meaning they have no central pair of microtubules and no dynein arms.
Basically divided by cilia that move (motile) and cilia that do not (primary or sensory).
3 dimensional view of 9 + 2 cilium, showing the plasma membrane that anchors the cilium to the epithelial layer and the basal body where the cilium is produced.
Cross-sectional schematic of a typical 9+2 “motile” cilium. The 9 refers to the 9 pairs of microtubule doublets inside the cell membrane. The 2 refers to the presence of a central pair of microtubules. Other important structures include the dynein arms, which are the functional units that make the cilium move.
3 dimensional view of 9 + 2 cilium, showing the plasma membrane that anchors the cilium to the epithelial layer and the basal body where the cilium is produced. In all there are more than 700 genes that code for proteins that make up the ciliary structure, including more than 200 in the axonemal shaft structures.
For our purposes, we will focus on “motile’ cilia and flagella. Structurally, they are nearly identical with flagella being slightly longer. Cilia, however, like to clump together and work collaboratively. They are anchored to the cell surface and their motility affects the environment around them. Flagella are usually found as singles, but may be doubles (bi-flagellates) or appear in groups. However, they are not anchored, tend to work independently and function by moving an organism through an environment.
Formerly considered the “janitors” of the respiratory system, motile cilia are now known to also have sensory functions.
Slides courtesy of Johnny Carson, PhD at UNC. We talked about dynein arms in an earlier slide. Dynein arms, in concert with a fuel source, in this case the nucleotide adenosine phosphate or ATP, are molecular motors.
Slides courtesy of Johnny Carson, PhD at UNC. We talked about dynein arms in an earlier slide. Dynein arms, in concert with a fuel source, in this case the nucleotide adenosine phosphate or ATP, are molecular motors.
Ciliary activity is very important beginning in the embryonic period
An interesting “hybrid” cilium found on the cells of the embyronic node combine 9+0 “sensory” activity with unusual motility. Rather than beating, these cilia “twirl” creating a leftward vortex in the fluid surrounding the node. This leftward nodal flow triggers a cascade of asymmetrical signaling that eventually results in the left-oriented “D” looping of the heart tube which sets the stage for eventual visceral asymmetry in normal development. In the absence of this trigger, organ placement and even development can be random.
An interesting “hybrid” cilium found on the cells of the embyronic node combine 9+0 “sensory” activity with unusual motility. Rather than beating, these cilia “twirl” creating a leftward vortex in the fluid surrounding the node. This leftward nodal flow triggers a cascade of asymmetrical signaling that eventually results in the left-oriented “D” looping of the heart tube which sets the stage for eventual visceral asymmetry in normal development. In the absence of this trigger, organ placement and even development can be random.
People with PCD have an equal chance of having situs solitus or situs inversus totalis
Somewhere between the ages of 4 and 5, it is possible to measure nasal NO as a screening tool for PCD
Lobectomy still popular in PCD. Very few children actually diagnosed before age 5. Some not until adulthood.
Lobectomy still popular in PCD. Very few children actually diagnosed before age 5. Some not until adulthood.
Lobectomy still popular in PCD. Very few children actually diagnosed before age 5. Some not until adulthood.
Lobectomy still popular in PCD. Very few children actually diagnosed before age 5. Some not until adulthood.
“ Classic” PCD
“ Classic” PCD
Because of similarities in the respiratory consequences of the two disorders, most PCD patients are followed in CF Clinics and the PCDF encourages that.
Because of similarities in the respiratory consequences of the two disorders, most PCD patients are followed in CF Clinics and the PCDF encourages that.
Kinesin molecular motors anterograde (on the way up); cytoplasmic dynein on the way down. IFT particles carry axomenal subunits to tip of the axoneme and also deposit protein cargoes along the microtubule.
Because of similarities in the respiratory consequences of the two disorders, most PCD patients are followed in CF Clinics and the PCDF encourages that.
Seven known genes—been looking since late 80’s PTC 124
Links to connective tissue diseases like Marfan syndrome. Possible PCD carrier/COPD connection.