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Primary ciliary dyskinesia
Synonym(s): PKD, immotile cilia syndrome, Kartagener's syndrome
Introduction
- Rare inherited defect in microtubule formation affecting respiratory and other cilia (eg urogenital tract, auditory canal) in pedigree dogs.
- Signs: early onset rhinosinusitis and recurrent bronchopneumonia. Infertility common. Situs inversus in 50%.
- Diagnosis: clinical signs, radiography, bronchoalveolar lavage, sperm samples, cilia function tests, electron microscopy of cilia.
- Treatment: symptomatic for recurrent bronchopneumonia.
- Prognosis: guarded to poor.
Presenting signs
- Signs continuous and progressive from birth or soon after.
- Continuous purulent rhinitis Rhinitis.
- Productive cough, dyspnea, hyperpnea.
- Sneezing, reverse sneezing.
- Infertility in older animals (male and female).
Acute presentation
- Acute episodes bronchopneumonia Lung: bacterial pneumonia superimposed on chronic cause dyspnea, cyanosis, possible death.
Age predisposition
- Most affected 1 day old to a few months.
- Occasionally several years old at presentation.
Breed/Species predisposition
- All reported cases are pedigree dogs:
- Border Collie Border Collie.
- English Setter English Setter.
- Doberman Pincher Dobermann.
- Chihuahua Chihuahua - Long Coat.
- English Springer Spaniel English Springer Spaniel.
- Golden Retriever Retriever: Golden.
- Old English Sheepdog Old English Sheepdog.
- English Pointer Pointer.
- Bichon Frise Bichon Frise.
- Dalmatian Dalmatian.
- Chow Chow Chow Chow.
- Miniature Poodle Poodle: miniature.
- Rottweiler Rottweiler.
- Chinese Shar Pei Chinese Shar Pei.
- Newfoundland Dalmatian.
- Alaskan Malamute Alaskan Malamute.
- Staffordshire Bull Terrier Staffordshire Bull Terrier.
- Dachshund Dachshund.
Cost considerations
- Moderate cost for prolonged antibiotics +/- hospitalization and oxygen therapy for acute exacerbations of bronchopneumonia.
Special risks
- Anesthetic.
- Same as severe bronchopneumonia.
- Hypoxia with hypo or normocapnia, ventilation-perfusion mismatch, poor clearance of bronchial secretions and ventral consolidation of lung lobes.
Take care placing in dorsal recumbency when awake or anesthetized - ventral consolidation of lung lobes increases risk of significant hypoxia.Maintenance on oxygen reduced respiratory drive because ventilation - perfusion mismatch results in hypocapnia - will need positive pressure ventilation.Do not administer cough suppressants such as narcotics during anesthesia or as premedication.
Pathogenesis
Etiology
- Normally autosomal recessive condition (occasionally possibly dominant) resulting in dysfunction of ciliated epithelia.
- Simple recessive inheritance in Old English Sheepdog. Mutated CCDC39 gene on chromosome 34 which is required for assembly of the inner dynein arm, the dynein regulatory complex and normal ciliary motility.
- NME5 gene frameshift variant in a family of Alaskan Malamutes with primary ciliary dyskinesia identified. Suspected autosomal inheritance.
Predisposing factors
General
- Neonatal bacterial rhinits.
Specific
- Inbreeding of pedigree dogs.
Pathophysiology
- Inherited abnormality of function and usually structure of cilia results in effects in all ciliated epithelia in body.
- Respiratory signs predominate due to poor mucociliary carpet clearance of mucus.
- Cilia in other organs also affected.
- Subclinical hydrocephalus Hydrocephalus and otitis media Otitis media in most cases.
- Wide variety of defects described involving various parts of the ultrastructure of the cilia. Some cases have normal cilia ultrastrucutre but abnormal orientation and motility.
- Cilia defects vary between breeds but consistent within one breed and between organs of one dog.
- Clinical signs similar for all described cilia defects.
- Note - Kartagener's syndrome is a specific form of PCD characterized by the triad of situs invertus (right-to-left transposition of thoracic and abdominal organs), chronic rhinitis and sinusitis and bronchiectasis.
Pathological process
- Ultrastructural and functional defect of cilia lining nose and airways → ineffective clearance of mucus → trapping of bacteria in lower airways and nose → recurrent bacterial infections → rhinosinusitis and bronchopneumonia → stimulation of further mucus secretions and weakening of bronchial walls → blockage of lower airways with mucus → air trapping, bulla formation, bronchiectasis and consolidation of ventral (dependent) lung lobes.
- Neonatal bacterial rhinitis especially associated with pasteurella Pasteurella multocida can → hypoplasia of nasal turbinates, atresia of frontal sinuses and rhinoliths.
- Ventilation - perfusion mismatch Ventilation-perfusion mismatching results from lung consolidation and airway obstruction → hypoxia and hypo or normocapnia.
- Pulmonary artery hypertension Pulmonary arterial hypertension (PHT) results from chronic respiratory disease → cor pulmonale Cor pulmonale in some chronic cases.
- Chronic bacterial infections provide a stimulus for hepatic production of serum amyloid A → amyloidosis Amyloidosis in some cases.
- Ciliary dysfunction in auditory tube → subclinical otitis media Otitis media in most dogs.
- Abnormal CNS ependymal cilia resulting in impaired CSF drainage or another poorly understood reason → subclinical hydrocephalus Hydrocephalus.
- Impaired ciliated function in spermatozoa → male infertility Infertility: male - overview in most cases.
- Postulated ineffective ciliary motility in embryo → random organ orientation → mirror image organs and thorax +/- abdomen (situs inversus) in 50% of cases. Mechanism may be simply genetic.
- Renal tubular dilation/fibrosis.
Timecourse
- Continuous respiratory signs gradually worsening with superimposed more acute episodes of severe bacterial bronchopneumonia.
Diagnosis
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Treatment
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Prevention
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Outcomes
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Further Reading
Publications
Refereed papers
- Recent references from PubMed and VetMedResource.
- Anderegg L et al (2019) NME5 frameshift variant in Alaskan Malamutes with primary ciliary dyskinesia. PLoS Genet 15(9) PubMed.
- Merveille A C et al (2014) Clinical Findings and Prevalence of the Mutation Associated with Primary Ciliary Dyskinesia in Old English Sheepdogs. JVIM 28(3), 771-778 PubMed.
- Durant A M (2008) What’s your diagnosis? Thoracic and Abdominal Situs Inversis Totalis. JAVMA 232(2), 197-198 PubMed.
- De Scally M, Lobetti RG & Van Wilpe E (2004) Primary ciliary dyskinesia in a Staffordshire bull terrier. J S Afr Vet Assoc 75(3), 150-152 PubMed.
- Neil J A et al (2002) Kartagener’s syndrome in a Dachshund Dog. JAAHA 38(1), 45-49 PubMed.
- Clercx C et al (2000) Use of ciliogenesis in the diagnosis of primary ciliary dyskinesia in a dog. JAVMA 217(11), 1681-1685 PubMed.
- Watson P J, Herrtage M E, Peacock M A & Sargan D R (1999) Primary ciliary dyskinesia in Newfoundlands. Vet Rec 144 (26), 718-725 PubMed.
- Schidlow D V (1994) Primary ciliary dyskinesia (the immotile cilia syndrome). Annals of Allergy 73 (6), 457-469, quiz 468-70 PubMed.
- Crager C S (1992) Canine primary ciliary dyskinesia. Comp Cont Educ Small Anim 14 (11), 1440-1444 VetMedResource.
- Edwards D F et al (1992) Primary ciliary dyskinesia in the dog. Probl Vet Med 4 (2), 291-319 PubMed.
- Edwards D F et al (1989) Familial immotile-cilia syndrome in English Springer Spaniel dogs. Am J Med Genetics 33 (3), 290-298 PubMed.
Other sources of information
- Johnson L (2000) Disease of the bronchus. In: Textbook of Veterinary Internal Medicine, 5th edn. Eds: S J Ettinger & E C Feldman. Philadelphia: W B Saunders Co. pp 1055-1061.