Kartagener’s Syndrome in a Dachshund Dog
Kartagener’s syndrome (KS) is a rare, congenital condition characterized by situs inversus, rhinosinusitis, and bronchiectasis. An underlying ciliary dysfunction (e.g., immotility or dyskinetic beating) produces most of the clinical signs seen in affected animals. This case report reviews the history, clinical signs, and diagnosis of KS in a male, long-haired dachshund. This is the first known report of KS, and thus primary ciliary dyskinesia, in this breed of dog.
Introduction
Kartagener’s syndrome (KS) is an uncommon congenital condition that has been reported in humans12 and several breeds of dogs.3–17 The pathognomonic features of this rare but medically important condition include situs inversus or mirror-image orientation of the thoracic or abdominal viscera (or both), rhinosinusitis, and bronchiectasis. The latter clinical findings are attributable to a primary ciliary dysfunction of the upper and lower airways; hence, more recently the term primary ciliary dyskinesia (PCD) has been applied to the disease.18 The ciliary dyskinesia results in airway infections (i.e., rhinosinusitis and broncho-pneumonia), ultimately making this condition serious and potentially life threatening.
Kartagener’s syndrome is a subset of PCD and can be diagnosed radiographically when situs inversus and bronchopneumonia are present; early bronchiectasis cannot be seen without contrast enhancement of the airways. The diagnosis of PCD is often more challenging, because not all patients have KS (i.e., situs inversus).18 Because PCD is the basis for the clinical syndrome, many body systems are affected. The tails of spermatozoa are modified cilia; therefore, sperm are often dysmotile, rendering males infertile.411 A common finding in dogs with primary ciliary dyskinesia is communicating hydrocephalus.417–20 Although the mechanism for producing hydrocephalus has not been elucidated, it was originally attributed to dysfunctional ependymal cilia.1 Definitive diagnosis of PCD usually necessitates ultrastructural analysis of respiratory cilia, but the fact that several body systems are affected often permits a probable diagnosis to be established using other diagnostic techniques. It has also been noted that some dogs with PCD have no ultrastructural ciliary lesions.418
Primary ciliary dyskinesia has been reported in several canine breeds.3–17 The purpose of the following report documenting a case of KS in a dachshund is to supplement the list of breeds previously reported to have this condition.
Case Report
A 4-year-old, castrated male, long-haired dachshund was presented to the University of Missouri-Columbia, Veterinary Medical Teaching Hospital (UMC-VMTH) with a life-long history of chronic respiratory problems. Originally, the dog had been surrendered by the breeder to an animal rescue organization at the age of 4 months because of pneumonia. At that time, the dog was adopted by the present owner. Prior to presentation to UMC-VMTH, the dog had been treated for multiple episodes of bronchopneumonia, primarily in the first 2 years of life. Complete blood counts (CBC) done during these episodes consistently revealed moderate to severe leukocytosis ranging from 20.3 to 43.4 × 103 white blood cells (WBC)/μL (reference range, 6.0 to 18.0 × 103 WBC/μL). Although most episodes were characterized by a mature neutrophilia (19.1 to 39.9 × 103 neutrophils/μL; reference range, 3.0 to 15.3 × 103/μL), one episode was associated with a moderately degenerative left shift (1,518 bands/μL; reference range, 0 to 300 bands/μL) and a mild anemia (hematocrit, 38.7%; reference range, 42.0% to 57.0%). No significant abnormalities were noted on corresponding serum biochemical profiles. Clinical signs during periods of bronchopneumonia included a fever of ≥104°F, moderate depression, violent episodes of forward and reverse sneezing, productive coughing, and moderate to severe, moist respiratory rales. There was a mucoid nasal discharge that, although present in time of relative health, would turn mucopurulent during times of clinical illness. Radiographs taken by the referring veterinarian revealed a mild to moderate alveolar pattern in the cranial ventral lung lobes, indicating bronchopneumonia as well as a moderate bronchointerstitial pattern suggesting a chronic form of pulmonary disease. The dog was historically treated with cefazolina (25 mg/kg body weight, intramuscularly [IM], q 6 hours) and recovered from each episode. Increased respiratory sounds and nasal discharge, although diminishing somewhat with antibiotic therapy, never ceased. Eight weeks after the initial visit to the referring veterinarian (i.e., at 6 months of age), bacterial cultures of a tracheal swab and a nasal swab grew Pasteurella multocida and Bordetella bronchiseptica, respectively. The dog was treated with enrofloxacinb (5 mg/kg body weight, per os [PO] q 12 hours for 14 days) but showed no improvement. Six months after the initial visit to the referring veterinarian, the dog was tested for titers against cryptococcosis, histoplasmosis, and blastomycosis. All results were negative. Nine months after the initial visit to the referring veterinarian, a regional allergy test (i.e., enzyme-linked immunosorbent assay [ELISA]) demonstrated serum immunoglobulin E (IgE) antibodies to many grasses, trees, and some food ingredients. Allergy injections were initiated at that time.
Clinical Examination
Upon presentation at the UMC-VMTH, the dog was bright and alert and was in ideal body condition at a weight of 7.7 kg. Abnormal physical examination findings included a bilateral serous nasal discharge, harsh lung sounds with crackles and moist rales, sinus arrhythmia, and a mild anisocoria. Complete blood count and serum biochemical profile results were within reference ranges. Thoracic radiographs showed evidence of a moderate bronchointerstitial pattern throughout all lung fields, indicating chronic respiratory disease. Bronchiectasis of the left cranial lung lobe bronchus was evident [Figure 1]. The ventrodorsal radiographs revealed a mirror-image reversal of both thoracic and abdominal organs or situs inversus totalis [Figures 1, 2]. The apex of the heart was pointing to the right of mid-line (i.e., dextrocardia), and the fundus of the stomach and the spleen were positioned on the right side. These radiographic findings in combination with the history were highly suggestive of KS. Ventrodorsal radiographs were repeated to assure that radiographic markers were placed appropriately.
Further Diagnostic Evaluation
Definitive diagnosis of PCD, the underlying defect of KS, relies on a respiratory mucosal biopsy and ultrastructural analysis of the cilia.18 In this case, biopsy was considered, but other methods of further diagnostic evaluation were chosen to reduce patient risk.18
Ten days prior to the scheduled day of diagnostic evaluation, prophylactic administration of cefadroxilc (22 mg/kg body weight, PO q 12 hours) was initiated. On the day of evaluation, the patient was premedicated with butorphanol tartrated (0.4 mg/kg body weight, IM). Thiopental sodiume (20 mg intravenously [IV]) was used for induction, and the dog was intubated and placed on isofluranef (1.5%) gas for maintenance of general anesthesia. A hygroscopic condenser humidifierg endotracheal tube attachment was used to humidify inspired air and thus prevent drying of the respiratory secretions.1821 The dog was placed in sternal recumbency, and fluid administration (100 mL of lactated Ringer’s solution, IV over 1 hour) was initiated.
Computed tomography of the nasal passages and brain was performed without the use of contrast. Results revealed bilateral nasal exudate with a ventral distribution [Figure 3]. Exudate was also identified in the basisphenoid sinuses. Nasal turbinates were normal. Moderate to severe, bilateral symmetrical hydrocephalus (in which the lateral cerebral ventricles appeared to be communicating) and mild, third-ventricular enlargement were evident [Figure 4].
Mucociliary scintigraphy was also performed. One drop of 99mTc-Macroaggregated Albuminh (99mTc-MAA) with an activity of 300 mCi was deposited at the tracheal bifurcation using a sleeved polystyrene catheter. Images were obtained at 5-minute intervals for 30 minutes.21 Images from this study showed no droplet movement (reference range, 2.8 to 9.8 mm per minute) [Figure 5].22 Both the computed tomography and mucociliary clearance studies were completed in approximately 1 hour. Due to prior castration, the semen of the dog could not be evaluated for sperm motility.
Discussion
A nasal respiratory biopsy was not performed because of owner preference and patient risk; thus, electron microscopy was not performed. The authors feel that the history, radiographs, computed tomography images, and mucociliary clearance study results support a diagnosis of PCD and KS in this dog. Computed tomography revealed hydrocephalus, which, as in most other cases of PCD, was not associated with clinical signs or cranial enlargement.20 The mild anisocoria found on physical examination is not a common finding among patients with primary ciliary dyskinesia and may be related to the hydrocephalus or may be a variation of normal. Mucociliary scintigraphy was consistent with PCD. Normal canine tracheal velocity averages 8.83±3.3 mm per minute.21 This dog has no mucociliary clearance, verified by the fact that there was no radiopharmaceutical droplet movement during the duration of the procedure.
Several factors in this mucociliary scintigraphy protocol may have contributed to false-positive results. It has long been suspected, and some investigations have established, that certain anesthetic agents have the ability to decrease mucociliary clearance.2324 In contrast, the potential for the specific agents used in this study, either individually or in combination, to cause the complete paralysis of the canine mucociliary apparatus has not been shown and would be unlikely. In fact, the reference range for normal adult canine tracheal velocity mentioned in this study was established during a prior study comparing various age groups of healthy beagles and their respective tracheal velocities while anesthetized with halothane.22 Additionally, a later study of mucociliary clearance in two PCD-affected English springer spaniels and eight normal dogs used an anesthetic protocol consisting of acepromazine and atropine for preanesthetic, thiamylal sodium for induction, and halothane for maintenance of general anesthesia. The two PCD-affected dogs were found to have no mucociliary clearance, while the eight normal dogs had mucociliary clearance velocities within the same reference range established in the beagle study just mentioned.19
Other potential reasons for false positives would include accidental deposition of the radioactive droplet into the secondary bronchi rather than the carina. Secondary bronchi have fewer ciliated epithelial cells as well as respiratory mucus that differs in depth and composition from that at the level of the carina. Additionally, droplet movement may have been deterred by endotracheal tube placement or length, or by an area of dried exudate on the tracheal mucosal surface.21
Although PCD may have been suspected in other patients presented to the University of Missouri College of Veterinary Medicine, mucociliary scintigraphy had not been performed in these cases. Thus, comparison of specific techniques and corresponding anesthetic protocols within this facility is not possible.
The dog in this report is still living and is 6 years old. Present treatment consists of the administration of cefadroxilc (22 mg/kg body weight, PO q 12 hours for 7 days) when symptomatic for bronchopneumonia, daily thoracic coupage, and airway humidification. Radiographs taken at 6-month to 1-year intervals are used to evaluate progression of pulmonary disease. Radiographs taken in December 1999, during the time of relative health, revealed bronchiectasis and a chronic bronchointerstitial pattern similar to that seen in Figure 1. Preanesthetic blood work (CBC and serum biochemistry) was performed on June 28, 2000 and was within reference ranges. General anesthesia (gas with a humidifier) and an abbreviated dental prophylaxis (30 minutes for entire procedure) were performed at that time. The procedure was performed without complication; however, a mild amount of purulent and hemorrhagic exudate was noted in the endotracheal tube when the dog was extubated. The dog was placed on cephadroxil and recovered without complications of fever and depression. The dog has had no episodes of fever and depression for several years; however, chronic sneezing and coughing are still present.
Various breeds of dogs have been reported with KS.3–17 The underlying primary ciliary dyskinesia and thus a lack of mucociliary clearance prevents the affected patient from clearing inhaled particles and bacteria from the upper and lower respiratory system. The disruption of this normal respiratory mechanism results in the clinical picture seen in affected animals, primarily chronic rhinosinusitis and recurrent bronchopneumonia. Additionally, other body systems that rely on normal ciliary motility may be affected, including the reproductive tract of affected males (i.e., immotile spermatozoa), the brain and ventricular system (i.e., hydrocephalus), and the middle ear because of its ciliated auditory canal (i.e., serous otitis).18 Primary ciliary dyskinesia is suspected to have an autosomal-recessive inheritance pattern.18 Breeds previously reported with PCD include the English springer spaniel,3 chow chow,4 Old English sheep-dog,5 border collie,7 English setter,8 Doberman pinscher,9 golden retriever,10 English pointer,11 Chihuahua,12 bichon frise,13 Dalmatian,14 miniature poodle,15 rottweiler,16 and Chinese shar pei.17 More recently, the condition has been reported in a Newfoundland dog.6 Because there are no known reports of PCD in the dachshund, it seems appropriate to supplement the previous list with the long-haired dachshund described in this case report.
Acknowledgment
The authors thank Dr. David F. Edwards from the College of Veterinary Medicine, University of Tennessee, for his advice on the diagnostic evaluation of this case and the writing of this manuscript.
Cefazolin; Marsam Pharmaceutical, Inc., Cherry Hill, NJ
Enrofloxacin; Bayer Corporation, Agriculture Division, Animal Health, Shawnee Mission, KS
Cefadroxil; Fort Dodge Laboratories, Inc., Fort Dodge, IA
Butorphanol tartrate; Fort Dodge Laboratories, Inc., Fort Dodge, IA
Thiopental sodium; Abbott Laboratories, North Chicago, IL
Isoflurane; Phoenix Pharmaceuticals, Inc., St. Joseph, MO
Hygroscopic condenser humidifier; Hudson Respiratory Care, Inc., Temecula, CA
99mTc Macroaggregated Albumin; Mid America Isotopes, Inc., Ash-land, MO
Citation: Journal of the American Animal Hospital Association 38, 1; 10.5326/0380045
Citation: Journal of the American Animal Hospital Association 38, 1; 10.5326/0380045
Citation: Journal of the American Animal Hospital Association 38, 1; 10.5326/0380045
Citation: Journal of the American Animal Hospital Association 38, 1; 10.5326/0380045
Citation: Journal of the American Animal Hospital Association 38, 1; 10.5326/0380045
Ventrodorsal radiographic view of the thorax in a 4-year-old, male, long-haired dachshund diagnosed with Kartagener’s syndrome. Note dilatation (i.e., bronchiectasis) of the left cranial lung lobe bronchus (arrows). Also note dextrocardia as the apex of the cardiac silhouette points to the right.
Computed tomography image of the nasal passages in a 4-year-old, male, long-haired dachshund diagnosed with Kartagener’s syndrome. Note the ventrally distributed nasal exudate bilaterally. Nasal turbinate atrophy is not present.
Mucociliary scintigraphy images at 5 and 30 minutes in a 4-year-old, male, long-haired dachshund diagnosed with Kartagener’s syndrome. The external markers are placed at the level of the trachea. The caudal marker is placed at the fifth intercostal space, or carina. The cranial marker is placed 20 cm cranial to the caudal marker. There is no movement of the radioisotope droplet compared to the external markers throughout the study. A tight droplet was not acquired; therefore, two distinct droplets are visualized on this study.
