primary ciliary dysfunction with kartageners syndrome

Abstract

Primary ciliary dyskinesia (PCD) is an autosomal recessive hereditary disease that includes various forms of ciliary ultrastructural defects. The most serious form is Kartagener syndrome (KS), which accounts for 50% of all cases of PCD. Kartagener‟s syndrome is a rare disorder and the prevalence is about 1 in 30,000. It is autosomal recessive ciliary disorder comprising the triad of situs inversus totalis, chronic sinusitis, and bronchiectasis. The defective movement of cilia leads to recurrent respiratory infections, and ear/ nose/ throat infections, and infertility. The diagnosis is made clinically and confirmed through electron microscopy, which reveals abnormalities of structural organization of the axoneme in cilia from respiratory epithelia and in spermatozoa. Underlying structural defects include 1) absent inner and/or outer dynein arms, 2) tubular defects, and 3) radial spoke defects. We hereby report a rare case of Kartagener‟s syndrome, in an infertile male with immotile sperms. The clinician should have a high index of suspicion, so as to make an early diagnosis. An early diagnosis helps in making the options for timely treatment of infertility may be offered and unnecessary evaluation is avoided.

Full text

E.A. Ashok Kumar, Pottala Shriya, Amritaa Thalla. -
A case report. IAIM, 2023; 10(6): 8-22.
Page 8
Case Report
A rare case of primary ciliary dyskinesia
with Kartagener’s syndrome - A case
report
E.A. Ashok Kumar1*, Pottala Shriya2, Amritaa Thalla3
1Professor, 2,3Intern,
Department of General Medicine, Maheshwara Medical College and Hospital, Chitkul (V),
Patancheru (M), Sangareddy Dist., Telangana, India
*Corresponding author email: ashokedla@gmail.com
International Archives of Integrated Medicine, Vol. 10, Issue 6, June, 2023.
Available online at http://iaimjournal.com/
ISSN: 2394-0026 (P) ISSN: 2394-0034 (O)
Received on: 4-6-2023 Accepted on: 15-6-2023
Source of support: Nil Conflict of interest: None declared.
Article is under creative common license CC-BY
How to cite this article: E.A. Ashok Kumar, Pottala Shriya, Amritaa Thalla. A rare case of primary
 syndrome - A case report. IAIM, 2023; 10(6): 8-22.
Abstract
Primary ciliary dyskinesia (PCD) is an autosomal recessive hereditary disease that includes various
forms of ciliary ultrastructural defects. The most serious form is Kartagener syndrome (KS), which
accounts for 50% s syndrome is a rare disorder and the prevalence is
about 1 in 30,000. It is autosomal recessive ciliary disorder comprising the triad of situs inversus
totalis, chronic sinusitis, and bronchiectasis. The defective movement of cilia leads to recurrent
respiratory infections, and ear/ nose/ throat infections, and infertility. The diagnosis is made clinically
and confirmed through electron microscopy, which reveals abnormalities of structural organization of
the axoneme in cilia from respiratory epithelia and in spermatozoa. Underlying structural defects
include 1) absent inner and/or outer dynein arms, 2) tubular defects, and 3) radial spoke defects. We
hereby report a rare case s syndrome, in an infertile male with immotile sperms. The
clinician should have a high index of suspicion, so as to make an early diagnosis. An early diagnosis
helps in making the options for timely treatment of infertility may be offered and unnecessary
evaluation is avoided.
Key words
Primary ciliary 

E.A. Ashok Kumar, Pottala Shriya, Amritaa Thalla. -
A case report. IAIM, 2023; 10(6): 8-22.
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Introduction
In 1933, Kartagener described the triad
consisting of dextrocardia, chronic vasomotor
rhinitis, and bronchiectasis as a distinct
clinicopathological entity. Kartagener
emphasized the familial and hereditary character
of this syndrome, which now bears his name,
Kartagener syndrome (KS) [1-7]. Kartagener's
syndrome is an autosomal recessive disorder
occurring with frequency of 1:30,000 to
1:40,000. It is characterized by the classic triad
of dextrocardia, bronchiectasis and sinusitis [8].
Primary ciliary dyskinesia (PCD)
Primary ciliary dyskinesia (PCD) is the name
that has evolved for a group of disorders caused
by microtubular defects in cilia and sperm. This
group of disorders was previously known as the
immotile cilia syndrome until it was discovered
that most of the cilia did move, albeit in an
uncoordinated or dyskinetic manner [9, 10].
These defects render the cilia in the respiratory
tract ineffective in clearing secretions [9, 11], a
condition that can lead to sinusitis, repeated
pulmonary infections, bronchiectasis,
obstruction, and air trapping [12-14]. Primary
ciliary dyskinesia is an autosomal recessive
disorder thought to affect between 1 in 15,000
and 1 in 30,000 persons [15].
Primary ciliary dyskinesia (PCD), previously
known as immotile cilia syndrome, is an
autosomal recessive hereditary disease that
includes various forms of ciliary ultrastructural
defects. The most serious form is Kartagener
syndrome (KS), which accounts for 50% of all
cases of PCD. PCD causes deficiency or even
stasis of the transport of secretions in the
respiratory tract. It favors the growth of viruses
and bacteria, and results in chronic and recurrent
infections. They may be suffering from
bronchitis, pneumonia, hemoptysis, sinusitis, and
infertility. The irreversible bronchial alterations
results in bronchiectasis and other chronic
conditions and infections, leading to chronic cor
pulmonale. The diagnosis is made clinically and
confirmed through electron microscopy. Since
there is no specific therapy for PCD, the
secondary infections should be treated promptly
with antibiotics and prophylactic measures
should be undertaken. Situs inversus occurs,
randomly, in 50% of the patients with PCD [16].
Primary ciliary dyskinesia (PCD) (MIM 242650)
is an autosomal recessive disorder with extensive
genetic heterogeneity [17]. Twenty to twenty-
five percent of these individuals with complete,
mirror-image situs inversus have ciliary
dyskinesia and respiratory symptoms
(Kartagener syndrome) as associated findings
[18].
PCD electron microscopy
In most cases with PCD, electron microscopy
reveals abnormalities of structural organization
of the axoneme in cilia from respiratory epithelia
and in spermatozoa. The other cases have
structurally normal but dysmotile or immotile
cilia. It is suggested that subtle structural
deficiencies of cilia may also be more common
[19]. The axoneme is composed of about 250
distinct proteins [20]. Electron microscopy of the
ciliary microtubules frequently reveals absence
or abnormalities of the outer and/or inner dynein
arms [21]. These arms are multisubunit protein
complexes with ATPase activity that promote
sliding between adjacent microtubules, the basic
action resulting in the beating of cilium and
flagellum. The axonemal dynein arms are
composed of heavy, intermediate, and light
dynein chains [22]. A defect in any one of these
proteins could lead to an abnormal dynein arm
and/or defective beating activity of the axoneme.
Blouin J. L., et al. [23] analyzed in a large
number of PCD families that revealed extensive
genetic heterogeneity. There was no single
genomic region harboring a common PCD locus
identified, but several potential chromosomal
regions were localized that could harbor genes
for PCD [23].
Till date, mutations in two genes are associated
with a minority of PCD/ Kartagener syndrome

E.A. Ashok Kumar, Pottala Shriya, Amritaa Thalla. -
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cases. These are genes coding for the dynein
axonemal intermediate chain 1 (DNAI1) [24-26]
and the dynein axonemal heavy chain 5
(DNAH5) [27]. Loss of function of the murine
DNAH5 dynein gene also causes PCD in the
mouse [28]. Other genes coding for axonemal
dyneins, such as the heavy chain DNAH9, the
intermediate chain DNAI2, and the light chain
LC8, were recently excluded as major causes of
PCD [29, 30]. Moreover, the FOXJ1 gene,
encoding a transcription factor involved in ciliary
development, was also excluded as common
cause of PCD [7, 31, 32].
PCD in neonates
Clinically it is characterized by onset in the
neonatal period of respiratory distress and
rhinitis [33], and if untreated, subsequent chronic
rhinosinusitis, recurrent respiratory infections
and bronchiectasis, and chronic secretory otitis
media [7, 34]. 50% of the patients have mirror
image organ arrangement [7, 34]. Other features
rarely described include oesophageal atresia and
gastro-oesophageal reflux [35]; complex
congenital heart disease often with [35]; biliary
atresia [36]; and hydrocephalus [37, 38].
The diagnosis
The diagnosis is important, to ensure that
aggressive airway clearance and appropriate
antibiotics are used to prevent the development
of bronchiectasis. The unnecessary and
inappropriate ear, nose and throat procedures are
avoided [7, 39].
The diagnosis is established by
1) Functional Studies, usually a direct
measurement of ciliary beat frequency on nasal
epithelial cells; and
2) From ciliary ultrastructure determined by
electron microscopy [7].
Underlying structural defects include
a) absent inner and/or outer dynein arms [40,
41],
b) tubular defects [42], and
c) radial spoke defects [43].
Rarely patients with a typical PCD clinical
phenotype have normal or near normal ciliary
beat frequency (CBF) and normal ciliary
ultrastructure, so the cause of their condition is
unexplained. Dysfunctional cilia in the middle
ear leave patients vulnerable to repeated otitis
media, and most suffer some degree of hearing
loss [44].
Sperm, which contain an identical microtubular
arrangement to cilia in their tails, have been
shown to be capable of fertilizing an egg [45] but
usually lack sufficient motility to reach one [46,
47]. The microtubular defects of PCD have also
been shown to cause motility problems in
phagocytic cells where microtubules are involved
in directed movement to capture pathogens [48-
50].
Case report
A 51-year-old male patient presented with
complaints of fever with chills and rigors of 4
days duration, purulent cough associated with
left sided non radiating chest pain and exertional
shortness of breath of 3 days duration.
History of presenting illness
Patient was apparently asymptomatic 4 days
earlier, then he developed fever with chills and
rigors, which was relieved on medication, no
history of night sweats, no diurnal variation. He
developed cough with purulent sputum of 3 days
which was insidious in onset, gradually
progressive, scanty in amount, blood tinged in
color, thick tenacious in consistency, showing
diurnal variation occurring more in the morning.
No history of wheeze, orthopnea, PND,
palpitations, and pedal edema, No history of
decreased urinary output. No history of loss of
consciousness. No history of weight loss. Patient
also had complaints of left sided chest pain
which was non radiating, and associated with
shortness of breath on exertion.
Past history
History of similar episodes 8-10 times a year in
the past. Not a known case of Diabetes mellitus,

E.A. Ashok Kumar, Pottala Shriya, Amritaa Thalla. -
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hypertension, thyroid disorders, tuberculosis,
hypertension, ischemic heart disease. Not a
known case of epilepsy/ CVA/ asthma/ COPD.
No history of drug allergies.
Family history
Patient is married for 26 years but has no
children. Patient was diagnosed with infertility
due to immotile sperms.
General Examination
Vitals - Temperature: 99 °F, PR: 70 /min, BP:
90/60 mmHg, RR: 20/min, SPO2: 98% with
oxygen support
Systemic Examination:
Upper Respiratory Tract
Nose: No nasal flaring, nasal septum central in
position, normal nasal cavities, no polyps,
ulcerations. Oral Cavity: Teeth-normal, Gums-
normal, tongue-normal, hard and soft palate-
normal, uvula-central, Sinus tenderness present
at frontal sinus.
Examination of Respiratory system
Inspection: Shape of Chest-normal. Trachea -
central in position.
Movements of the chest: equal on both the sides,
No usage of accessory muscles, No inter costal
indrawing, no engorged veins, no sinuses, no
inter costal scars or swellings.
Palpation: All inspectory findings were
confirmed. No local rise of temperature and
tenderness. No bony swelling or tenderness.
Measurements:
Circumference: Right hemithorax- inspiration:
40.5cm, expiration: 38cms,:
Left hemithorax inspiration: 39.5cm, expiration:
37 cm
AP: Transverse Ratio  5:7, Transverse diameter-
35 cm, Antero-posterior diameter  25 cm
Vocal fremitus: Increased in left supraclavicular,
mammary and inframammary areas.
Percussion: Dull note on left supaclavicular,
mammary and inframammary areas.
Auscultation: Bronchial breath sounds in left
suprascapular, infrascapular and mammary areas
are heard, Adventitious sounds: Lt. Side - coarse
leathery crepitations heard at infraaxillary,
interscapular and infrascapular. Vocal
Resonance: Increased on left supraclavicular,
mammary, inframammary areas.Rt. Side- normal
bronchovesicular breathing present and there
were no advetitios sounds
Cardio vascular system: Apex not felt on left
side, Heart sounds -S1, S2 heard distant in 5th
left intercostal space, but better heard on Rt. side,
no murmurs.
P/A: Soft, with normal bowel sounds
CNS: NAD
Investigations
Viral markers: Hepatitis C Virus Antibody (Anti
HCV) - Non reactive, HIV 1 and 2 AG/AB - Non
reactive, Hepatitis B Surface Antigen (HBsAg) -
Non reactive, Prothrombin Time (PT) with INR -
17.10 sec, Glycated Hemoglobin (HbA1C) -
5.6%, CBP-Hemoglobin 12.40 gm/dL, Total
RBC Count - 4.38 Million/Cu mm, Packed Cell
Volume (PCV) - 37.20%, RBC Indices - MCV-
84.90 fL, MCH - 28.30 pg, MCHC - 33.3 g/dL,
RDW-CV - 13.30%, Platelet Count - 2.6 L/cu
mm, Mean Platelet Volume (MPV) - 9.50 fL,
Total WBC Count - 17780 cells/cu mm
Differential Count  Neutrophils - 86.8%,
Lymphocytes - 7%, Eosinophils - 0.10%,
Monocytes - 6%, Basophils - 0.10%; Absolute
Counts - Neutrophil 15430 cells/cu mm,
Lymphocyte 1250 cells/cu mm, Eosinophil 20
cells/cu mm, Monocyte 1060 cells/cu mm,
Basophil 20 cells/cu mm
Peripheral Smear - RBC- Normocytic
normochromic, WBC - Neutrophilic
leukocytosis, Platelets on Smear-Adequate,
Procalcitonin - 0.787 ng/ml., NT PRO BNP -
1107 pg/ml.
Bronchoalveolar Lavage (BAL) Bronchial
Washing For AFB -No Acid Fast Bacilli Seen,
Fungal Smear (KOH Mount) for fungal
elements-Negative For Fungal Elements
X-PERT MTB/RIF Assay-Not detected, Sputum
for C/S - Staph Aureus, Klebsiella grown
(vancomycin resistance)
ECG in left sided leads - Normal sinus rhythm,
Rate- 76 bpm, Lead 1 -   
     
       
S/O Dextrocardia; ECG in right sided leads:

E.A. Ashok Kumar, Pottala Shriya, Amritaa Thalla. -
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    n Right sided
precordial leads.
X-ray Chest PA View (Figure - 1) shows
dextrocardia with consolidation left upper lobe
Figure – 1: X Ray Chest P A View shows
dextrocardia with consolidation left upper lobe.
CT Scan Chest (Figure - 2, 3)
Situs inversus with dextrocardia and liver on left
side. Discrete and confluent foci of consolidation
noted in apicoposterior and lingular segment of
left upper lobe. Areas of breakdown in
consolidation of apicoposterior segment of left
upper lobe. Centrilobular nodules with tree in
bud appearance noted diffusely in the left upper
lobe (Figure - 2, 3).
Figure – 2: Shows situs inversus with
dextrocardia and liver on left side. Discrete and
confluent foci of consolidation noted in
apicoposterior and lingular segment of left upper
lobe.
Figure – 3: Shows areas of breakdown in
consolidation of apicoposterior segment of left
upper lobe. Centrilobular nodules with tree in
bud appearance noted diffusely in the left upper
lobe.
Varicoid and cystic bronchiectatic changes noted
in the lingular segment of the left upper lobe with
peribronchial thickening. Mild central
bronchiectasis noted in bilateral lower lobes with
peribronchial thickening. Small consolidation
focus is also noted in the medial basal segment of
the right lower lobe. GGOs with interlobular
septal thickening noted in the lingular segment of
the left upper lobe. Subpleural paraseptal
emphysematous changes in the left upper lobe.
Left mild pleural effusion of thickness 1.7cm
(Figure - 4).
Figure – 4: Shows varicoid and cystic
bronchiectatic changes in the lingular segment.
Subpleural paraseptal emphysematous changes in
the left upper lobe. Left mild pleural effusion of
thickness 1.7 cm.

E.A. Ashok Kumar, Pottala Shriya, Amritaa Thalla. -
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CT Thoracic Angiogram (Figure - 5, 6)
Bronchial arteries: Right bronchial artery-origin-
D6 vertebral level 12 o'clock position -3.5mm
tortuous traceable up to right hilum. Left
bronchial artery -origin- D6 vertebral level 3
o'clock position- 3.9mm at ostium, tortuous
traceable up to left hilum. Another tortuous
bronchial artery arising from an aorta at D7 level
measuring 2.8 mm noted traceable to the right
hilum (Figure - 5).
Figure – 5: Shows origins of Bronchial arteries:
Right bronchial artery and Left bronchial artery.
Ascending aorta is on left, and shows normal
caliber & enhancement. Arch of aorta is on the
right side, and shows normal caliber &
enhancement. Brachiocephalic, left subclavian &
left common carotid arteries arise from the arch
of aorta. Brachiocephalic divides into the right
subclavian & right common carotid artery. The
both vertebral origins are normal in course and
caliber (Figure - 6).
2D Echo Doppler study
MVF: EAE/A: 0.6/0.7m/sec
AV: AJV: 1.4 m/sec
PV: PJV: 1.0 m/sec, TRJV 2.4 m/sec, RVSP:
34mmHg
Colour Flow Imaging: Trivial MR/TR.
Conclusion: Dextrocardia, No RWMA of LV,
Fair LV Systolic function, Grade 1 LV Diastolic
Dysfunction, Trivial MR/TR/NO PAH, No
PE/Clot
Figure – 6: shows Ascending aorta is on left.
Arch of aorta is on the right side.
Brachiocephalic, left subclavian & left common
carotid arteries arise from the arch of aorta.
Brachiocephalic divides into the right subclavian
& right common carotid artery.
CT Scan of Paranasal sinuses (Figure - 7, 8)
Frontal sinus not pneumatized
bilaterally.Anterior ethmoid air cells - Mild
mucosal thickening bilaterally.Volume reduction
in bilateral maxillary sinuses with mild mucosal
thickening and bony remodeling of sinus walls
suggestive of chronic sinusitis. Sphenoid sinus -
mild mucosal thickening bilaterally.Nasal septum
-mild deviation of nasal septum towards the left
side.
Impression - Bilateral chronic maxillary sinusitis
(Figure - 7, 8).
Figure – 7: Shows Frontal sinus not
pneumatized bilaterally. Bilateral chronic
maxillary sinusitis.

E.A. Ashok Kumar, Pottala Shriya, Amritaa Thalla. -
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Figure – 8 Shows Frontal sinus not pneumatized
bilaterally. Bilateral chronic maxillary sinusitis.
Diagnosis: Kartagener syndrome with Left
Upper Lobe consolidation
Treatment given
1. Oxygen
2. IV fluids
3. Tab. MEROPENEM 200 mg twice daily at
8am-8pm for 10 days
4. Tab. LINEZOLID 600 mg twice daily for
10 days
5. Tab. PAN 40 mg once daily -  
before breakfast
6. Tab. SUPRADYN 1 tablet once daily for
10 days
7. Syp. MUCOLITE 10 ml twice daily for 1
week
8. Nasoclear Saline nasal spray P/N thrice
daily
Discussion
Individual clinicians will differ in the order of
tests performed. This will also depend on the
facilities available. Two points should be
stressed:
1) it is important not to be confused by
abnormalities that are secondary to an underlying
infection and thus might confuse the diagnostic
work up [51, 52]and,
2) that more than one abnormality of host
defence may co-exist in the same person.
Need for repeated tests
Indications: any suspicion of secondary ciliary
dyskinesia; atypical clinical picture; and
suspicion of primary orientation defect. If
structural studies are diagnostic of PCD and the
clinical picture is classical, a repeat sample
should be obtained early. Secondary ciliary
dysfunction is common in population. Hence, a
repeat sample should be obtained several months
after the first sample to avoid confusing primary
and secondary ciliary dyskinesia. Intensive and
prolonged treatment of any inflammation and
infection should be undertaken before the second
sample is taken. If possible, a further sample
should be taken from another part of the
respiratory tract, e.g. at bronchoscopy. There is
some evidence that spermatozoal tails are under
the control of different genetic loci [53, 54], so
semen analysis may not reflect respiratory cilia.
Pneumonia with no history of maternal illness or
prolonged rupture of the membranes; and for any
baby with significant and prolonged nasal
discharge.
The saccharin test
Indications: screening for PCD. This test is not
suitable for small children who will not sit still
for an hour [55]. A 12 mm particle of saccharin
is placed on the inferior nasal turbinate 1 cm
from the anterior end. The patient sits quietly
with the head bent forward, and must not sniff,
sneeze, cough, eat or drink for the duration of the
test. The time to tasting saccharin is noted and is
a measure of nasal mucociliary clearance
(NMCC). If after 60 min, no saccharin taste is
observed, a saccharin particle is placed on the
tongue to check that the patient can truly taste
saccharin.
Presentations of PCD
In view of the high cost and lack of availability
of diagnostic tests for PCD, most physicians
undertake other screening investigations
appropriate to the presenting symptom(s) first.
The varying patterns of symptoms have been
reviewed [34, 56]. In one series [56], the age at
presentation varied between 4 months and 51 yrs,
with chronic sputum production and nasal
symptoms being the main presenting features. In

E.A. Ashok Kumar, Pottala Shriya, Amritaa Thalla. -
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Page 15
a paediatric series [34], cough, sinusitis and otitis
were universal. In both the series [34, 56],
dextrocardia was present in 50% of the patients.
Depending on the presentation, the tests may
include sweat testing, immunoglobulins and
subclasses, pH probe, etc. The nature of the
investigations will depend on the clinical
presentation. A diagnosis of PCD should be
considered under a number of clinical features;
no one feature is an absolute indication, and a
combination of clinical features may be more
suggestive than one single indication.
Indications for screening for PCD
1) A baby with neonatal respiratory distress: it
would seem reasonable to recommend screening
for PCD
a) for term babies born by vaginal delivery
who become tachypnoeic as to require
treatment and who have no conventional
risk factors for transient tachypnoea of the
newborn;
b) for babies with neonatal pneumonia with
no history of maternal illness or prolonged
rupture of the membranes; and
c) for any baby with significant and
prolonged nasal discharge.
2) Child/adult with bronchiectasis of unknown
cause:
a) The first consideration is to demonstrate
that bronchiectasis is present;
the chest radiograph is notoriously
insensitive, and bronchography has been
replaced by high-resolution, thin-section
computed tomography.
b) The anatomical fact of bronchiectasis
having been established, investigations to
determine the cause should be pursued.
The screening tests
The "first wave" tests
The "first wave" tests are chosen because of the
availability and prevalence of the underlying
condition. These will include 1. sweat test (often
with nasal potentials, and cystic fibrosis
genotype),2. immunoglobulins (Ig) including IgE
and IgG subclasses, 3.antibody responses,
4.serological evidence of previous adenovirus or
mycoplasma infection, 5.autoantibody screen
(rheumatoid factor, antinuclear factor) and
6,alpha-1 antitrypsin levels.
The "second wave" tests
If the "first wave" tests are negative, then
"second wave" investigations to be considered
include 1.fibreoptic bronchoscopy (particularly
for disease localized to one lobe), 2.oesophageal
pH monitoring; 3.saccharin test in older children
and adults, and 4.nasal brushings for ciliary
studies; 5.neutrophil function tests; and T-cell
subsets. The choice of second wave
investigations will depend on any associated
features present. It should be noted that more
than one immunological abnormality can exist,
and pursuing further investigations should be
considered even if one putative abnormality is
found.
3) Child with severe or atypical asthma: in
this case, it is important to consider whether the
diagnosis is correct. Many would like to perform
the "first wave" tests above on most children who
are not responding to high dose inhaled steroids,
and in addition exclude a vascular ring by
performing a barium swallow and
echocardiogram. Fibreoptic bronchoscopy would
also need consideration. PCD also enters the
differential diagnosis.
4) Child with upper airway disease: nasal
polyps, with or without severe sinusitis, may be
the presenting feature of cystic fibrosis, and
mandates a sweat test. If this is negative, then
PCD should be excluded. It would be impossible
to screen all children with fluid in the middle ear;
but the child with persistent serous otitis media,
persistent discharge after grommet insertion, or
co-existent lower airway infection should be
screened for PCD. This has management
implications (below).
5) Infertility clinic: All males with spermatozoa
that are either immotile or of reduced motility
should be considered for screening for PCD even
if there are no upper or lower respiratory tract

E.A. Ashok Kumar, Pottala Shriya, Amritaa Thalla. -
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Page 16
symptoms; and females who are deemed on
standard criteria to be infertile or subfertile
without an obvious anatomical or hormonal
cause, particularly if other features of PCD are
present. Fertility does not exclude the diagnosis
of PCD in males.
6) Other clinical situations: the upper and lower
respiratory tract features of PCD may be
inconspicuous or not reported by the patient who
has become accustomed to the lifelong
symptoms; the possibility of the condition should
be considered if there are combinations of
suggestive features, including dextrocardia,
disorders of laterality, deafness, hydrocephalus,
biliary atresia, and congenital heart disease.
The diagnostic criteria
As with all clinical medicine, the key is a high
index of suspicion, with the performance of a
detailed history and physical examination.
Attention must be paid to the timing of onset of
symptoms (particularly the onset at birth,
compared to within the first few weeks of birth).
There are no definitively diagnostic features on
history or examination, so diagnosis rests on
laboratory testing. This should include an
assessment of both structure and function.
There are a number of ways to assess
mucociliary clearance, including observation of
particle movement and isotope clearance from
the lower respiratory tract. Clinically, the most
useful is the saccharin test, which is a cheap and
easy procedure that can be used to screen older
children and adults; a properly performed normal
test excludes the diagnosis and obviates the need
for more sophisticated testing [57]. An abnormal
test must be investigated by ciliary analysis.
Ciliary disorientation was recently described as a
possible variant of PCD [58, 59]. Patients
typically have cilia with normal structure and
normal or near normal beat frequency, but their
cilia lack efficacy because their beat direction is
disoriented. It has been suggested that this is a
genetically conferred abnormality of the basal
bodies or possibly of the anchoring mechanism,
preventing normal orientation of cilia. This has
to be measured by electron microscopy from
cross-sections of ciliary shafts or basal feet.
Lines are drawn through the central pairs, or to
transect the midpoint of base and apex of the
basal feet, of a number of cilia arising from a
single cell. These lines should normally all be
roughly parallel with each other, and thus make a
similar angle with a second line drawn vertically.
The standard deviation (SD) of these angles
should, therefore, be small. An SD can be
calculated for a number of cells in the sample
and a mean SD computed. Disorientation results
in a larger SD. Typical normal values are SD 10
15% and for PCD with disorientation, 2025%
[60, 61].
However, ciliary disorientation can be transient,
secondary to infection, so a second sample is
taken after treatment to reduce inflammation and
eradicate infection before a diagnosis of PCD
secondary to disorientation is made.
Measurements of nasal and exhaled nitric
oxide
Nitric oxide (NO) is produced from the upper
and lower respiratory tract. Exhaled NO is
increased in uncontrolled asthma [62, 63] and
bronchiectasis [64],but normal in cystic fibrosis
[65,66]. In patients with PCD, nasal [67, 68] and
tidally exhaled [68] NO is very low. These
findings are currently unexplained. It would be
premature to suggest that measurement of NO
can be used to diagnose or exclude PCD, or even
as a screening test. However, if NO is found to
be unexpectedly low in a patient thought to have
uncontrolled asthma or bronchiectasis of
unknown cause, then the diagnosis of PCD
should be actively excluded. Further research is
needed, but currently, we cannot recommend a
definite clinical role for NO measurements in the
diagnosis of PCD.
Since the underlying defect in PCD cannot be
corrected, the mainstay of therapy remains
effective bronchial toilet and antibiotic therapy
of superinfection as well as such prophylactic
measures as vaccination against influenza virus
and S. pneumonia [14].

E.A. Ashok Kumar, Pottala Shriya, Amritaa Thalla. -
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The diagnosis is important, to ensure that
aggressive airway clearance and antibiotics are
used to prevent the development of
bronchiectasis, and that inappropriate ear, nose
and throat procedures are avoided [9, 39]. The
diagnosis is established firstly, by functional
studies, usually a direct measurement of ciliary
beat frequency on nasal epithelial cells; and
secondly, from ciliary ultrastructure determined
by electron microscopy [7]. Underlying
structural defects include absent inner and/or
outer dynein arms [40, 41], tubular defects [42],
and radial spoke defects [43].
Rarely patients with a typical PCD clinical
phenotype have normal or near normal ciliary
beat frequency (CBF) and normal ciliary
ultrastructure, so the cause of their condition is
unexplained [69].
1) In the new-born period: unexplained
tachypnoea or neonatal pneumonia, particularly
in a term baby with no risk factor for congenital
infection [33]. Other presentations at this age
include the newborn with rhinitis; dextrocardia
or complete mirror image arrangement with
structurally normal heart; complex congenital
heart disease, particularly with disorders of
laterality [35]; oesophageal atresia or other
severe defects of esophageal function [35];
biliary atresia [36]; hydrocephalus [37, 38]; and
positive family history.
2) In the infant and older child: "asthma" that
is atypical or not responsive to treatment; chronic
particularly wet cough, and sputum production in
the older child who is able to expectorate (these
are particularly important symptoms whose cause
should always actively be pursued in childhood);
severe gastroesophageal reflux; bronchiectasis;
rhinosinusitis (very rarely with nasal polyps) [34,
70-72]; chronic and severe secretory otitis media,
particularly with continuous discharge from the
ears after grommet insertion; and diagnosis in
more severely affected sibling [40, 73].
3) In the adult presentation as in the older
child, but also female subfertility including
ectopic pregnancy [1], and male infertility with
spermatozoa that are immotile or of reduced
motility. It should be noted that infertility in
males is by no means invariable [74].
Management
Bronchopulmonary toilet is a cornerstone of
PCD therapy. Patients with primary ciliary
dyskinesia are totally reliant on two mechanisms
for secretion removal: coughing, which is almost
as effective as the mucociliary elevator in
removing secretions [14, 75, 76], and gas-liquid
pumping, which involves patients manipulating
their secretions by sucking up or down in the
back of their throats. Patients can benefit by
clearing secretions by these methods every two
to three hours while awake. Physiotherapy, such
as postural drainage and percussion, may be
helpful on an as-needed basis but are not as
effective as cough [14].
A relative innovation in chest physiotherapy, the
forced expiration technique, may be taught to
these patients. Forced expiration, or the "bovine"
or "huffing" cough, is done without glottic
closure and applies a shearing force to secretions
that aids in expectoration [75].
A variety of medications are used to relieve
patients' symptoms. Various authors suggest the
use of saline aerosols and hypertonic saline
solution, methylxanthines, guaifenesin, and
bromhexine hydrochloride to improve clearance
[13, 14, 44, 75, 77].
Obstruction can be relieved with, Beta-agonists.
Decongestant use may relieve sinusitis;
mucolytics and adequate hydration may keep
secretions from becoming too tenacious to move;
and rhinorrhea may be relieved with
anticholinergic aerosols. Surgical interventions
include trimming the inferior turbinate to relieve
sinus obstruction or meatal antrostomies, in
which larger exits are drilled into the sinuses for
mucus to drain through by gravity [13].
Patients with PCD should have a culture and
sensitivity workup and receive antibiotics at the

E.A. Ashok Kumar, Pottala Shriya, Amritaa Thalla. -
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Page 18
first sign of infection because the progression of
chronic pulmonary infection to bronchiectasis is
one of the worst consequences of the disease
[13]. Some patients benefit from periodic courses
of antibiotics as a preventive measure [14].
Despite the significant morbidity and discomfort
associated with PCD, the disease progresses
more slowly than cystic fibrosis and can be
slowed even more by educating patients and
treating infection promptly. Overall, it has a
better prognosis than cystic fibrosis [44], and
these patients may go on to lead relatively
normal lives and remain stable for long periods
of time [12, 14].
Most infertile patients with KS have a normal
spermatozoid count, but with a structural defect
and a complete lack of motility [1]. Arge [78]
first reported three male patients with this
syndrome having immotile spermatozoa and
sterility. Male patients with KS invariably
present infertility, while women present reduced
fertility [1]. Infertility in male KS patients is due
to diminished sperm motility, while in females it
is due to defective ovum transport because of
dyskinetic motion of oviductal cilia, suggesting
that the ciliated endosalpinx is essential for
human reproduction [78].
The development of assisted reproductive
techniques has allowed rational treatment for
these patients. Pregnancies were successful using
subzonal insemination (SUZI) and
intracytoplasmic sperm injection (ICSI). If there
is no sperm motility, ICSI may be the most
appropriate treatment and if sperm motility is
present, a trial of in vitro fertilization (IVF)
should be considered [79].
Conclusion
Primary ciliary dyskinesia (PCD) is the name
that has evolved for a group of disorders caused
by microtubular defects in cilia and sperm. In
most cases with PCD, electron microscopy
reveals abnormalities of structural organization
of the axoneme in cilia from respiratory epithelia
and in spermatozoa. The most serious form of
PCD is Kartagener syndrome (KS). PCD causes
deficiency or even stasis of the transport of
secretions in the respiratory tract. It favors the
growth of viruses and bacteria, and results in
chronic and recurrent infections. The diagnosis is
essentially clinico-radiological, with variation in
view of azoospermia and oligospermia. As with
all clinical medicine, the key is a high index of
suspicion, with the performance of a detailed
history and physical examination. In view of the
high cost and lack of availability of diagnostic
tests for PCD, most physicians undertake other
screening investigations appropriate to the
presenting symptom(s) first. Since there is no
specific therapy for PCD, the secondary
infections should be treated promptly with
antibiotics and prophylactic measures should be
undertaken. Bronchopulmonary toilet is a
cornerstone of PCD therapy.
But infertility is also an important aspect which
needs to be addressed in evaluation so that they
may beget children. An early diagnosis helps in
such patients so that the options for timely
treatment of infertility may be offered and
unnecessary evaluation is avoided. Now the
development of assisted reproductive techniques
has allowed rational treatment for these patients.
Pregnancies were successful using subzonal
insemination (SUZI) and intra cytoplasmic sperm
injection (ICSI).
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