It results in mucus accumulation and bacterial colonization of the respiratory tract which leads to chronic upper and lower airway infections, organ laterality defects, and fertility problems. We review the respiratory signs and symptoms of PCD, as well as the screening tests for and diagnostic investigation of the disease, together with details related to ciliary function, ciliary ultrastructure, and genetic studies. In addition, we describe the difficulties in diagnosing PCD by means of transmission electron microscopy, as well as describing patient follow-up procedures. The prevalence of PCD ranges from , to ,, PCD occurring most frequently in families with consanguineous marriages. Evidence suggests that the diagnosis of PCD is often delayed, which is mainly due to a failure to recognize the disease and the need for sophisticated technical resources for PCD screening.
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The incidence of PCD ranges from , to , Since PCD causes deficiency or even stasis of the transport of secretions throughout the respiratory tract, it favors the growth of viruses and bacteria. As a result, patients have lifelong chronic and recurrent infections, typically suffering from bronchitis, pneumonia, hemoptysis, sinusitis, and infertility.
Bronchiectasis and other chronic conditions infections can be the end result of the irreversible bronchial alterations, leading to chronic cor pulmonale and its consequences. Only half of the patients affected by PDC present all of the symptoms, a condition designated complete KS, compared with incomplete KS, typically defined as cases in which situs inversus does not occur.
The diagnosis is made clinically and confirmed through transmission electron microscopy. Since there is no specific therapy for PCD, it is recommended that, upon diagnosis, secondary infections be treated with potent antibiotics and prophylactic interventions be implemented. In this paper, we report six cases of PCD five cases of complete KS and one case of KS and review the related literature, focusing on the diagnostic, therapeutic and clinical aspects of this disease. Keywords: Kartagener syndrome; Ciliary motility disorders; Bronchiectasis; Dextrocardia.
Introduction Primary ciliary dyskinesia PCD , previously known as immotile cilia syndrome ICS , belongs to a relatively small group of genetic disorders that follow an autosomal recessive inheritance pattern. Subsequently, in , 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. Subsequently, Afzelius and Eliasson, studying the ciliary ultrastructural changes resulting from this disease, observed the absence of dynein arms in the respiratory ciliary axoneme and in the sperm tail axoneme, the latter resulting in sperm immotility. According to various population-based studies, the incidence of PCD ranges from , to , live births. The authors address issues regarding pathophysiology, heredity, and clinical manifestations, as well as diagnostic and treatment methods.
Of the six patients studied, four were male and two were female. The mean age was All patients had a history of chronic respiratory tract infections, of the upper and lower respiratory tract chronic sinus diseases and recurrent pneumonia, respectively.
Chronic otitis was also a common manifestation. The male patients reported abundant mucopurulent expectoration, sometimes accompanied by hemoptysis, with chronic evolution. There were two siblings Cases 5 and 6 who also presented digital clubbing. Table 1 shows the clinical data of the patients. Simple chest X-rays revealed thickening of the bronchial walls, atelectasis, and findings suggestive of bronchiectasis in all of the patients, and situs inversus was observed in five cases Figure 1. In the first four cases of the series, bronchograms were performed in two phases: first on one side and then, after an interval of approximately thirty days, on the other side.
In the last two cases, bronchograms were replaced by high-resolution computed axial tomography. Both tests revealed several types of bronchiectases cylindrical, cystic, and varicose that were mainly located in the lower lobes, in the left middle lobe, and in the right lingula due to the situs inversus Figures 2, 3a, 3b, and 3c.
The first five cases of the series presented dextrocardia, and Case 5 also presented situs inversus totalis Figure 3d. Case 6 was the only one to present levocardia. Cases 1 and 4 involved childless adult female patients, although fertility was not investigated. The four remaining cases involved male patients, all of whom presented strong clinical signs of infertility.
The investigation of infertility was made through sperm counts in Cases 3, 5, and 6. In the six cases, the spirometry results showed varying degrees of obstruction, with a decrease in forced vital capacity, without response to the bronchodilator. Only one patient Case 5 underwent biopsy of the nasal and bronchial mucosas: the nasal biopsy was performed in the left lower turbinate under local anesthesia, and the biopsy of the bronchial mucosa was performed by fiberoptic bronchoscopy, also under local anesthesia.
The material was fixed with glutaraldehyde and, when examined under transmission electron microscopy, was found to be compatible with PCD. Despite being palliative, the treatment was administered only after other pulmonary suppuration syndromes, such as cystic fibrosis, had been ruled out.
The evolution of the accompanying infections was satisfactory after the introduction of antibiotic treatment regimens, vaccination, the use of expectorants, hydration, postural drainage, and, occasionally, bronchoscopy to aspirate secretions. Discussion Chronic infections of the upper respiratory tract, such as sinusitis, rhinosinusitis, and otitis, as well as chronic infections of the lower respiratory tract, such as bronchitis, rhinobronchitis, infected bronchiectasis, or recurrent pneumonia, are quite common in Brazil.
When the results of the various clinical, laboratory, and imaging approaches are negative for these etiologies, other less prevalent clinical entities should be considered. When, in addition to the clinical profile, patients present situs inversus, they are classified as having KS, which is currently a form of presentation of PCD. All patients presented quite accentuated respiratory symptoms that had been evolving since early childhood. These chronic pulmonary suppuration syndromes were recurrent and refractory to treatment, worsening after puberty.
Hemoptysis and purulent expectoration were more abundant in the four male patients. Of the six patients studied, five presented situs inversus. The only patient without situs inversus presented a clinical profile similar to that of the other patients. This author showed, in , that patients with KS have defects in the ultrastructure of the cilia and in the sperm tail, these alterations having the end result of irremediably impairing the motor skills Therefore, male infertility is another clinical manifestation in indi-the cilia are defective, the rotation occurs, but viduals with this disease.
When with PCD have situs inversus. Therefore, alterations can be found at the normal ciliary activity and have direct consequences following sites: in the epithelium of the deferent on mucociliary clearance, thus predisposing to recur-ducts; in the uterine tubes; in the endometrium; in rent respiratory infections. This results in chronic the corneal endothelium; in the ependyma; in the obstructive-suppurative disease of the respiratory cilia of the olfactory epithelium mitral cells and of tract.
Found in all races and in both genders, PCD the crests; in the ampulla and cells of Corti of the inner ear; and in the epithelium of the respiratory tract. Consequently, ciliary function must be investigated in these organs. Of those, three were confirmed as being infertile and one, aged 21 years, refused to be submitted to a sperm count. The other two cases involved childless adult female patients. For these reasons, it is believed that PCD is an autosomal recessive genetic alteration.
Transmission electron microscopy was employed in only one case. The radiological findings reported here are also of great value in cases of suspicion of PCD and are in concordance with the data in the literature.
Despite being universally accepted as the best method for the diagnosis and surgical evaluation of bronchiectasis, bronchogram, initially described by Sicard and Forestier in , has lately been less often employed. This is due to several factors: allergic reactions to the contrast medium; bronchospasm the procedure causes extreme discomfort to the patient ; the test is performed on one lung at a time the study of the other lung can only be performed after a two- to four-week interval ; and difficulty of interpretation by less experienced radiologists.
However, the most important factor was the advent, in the s, of computed tomography, which is currently the method of choice for the study of bronchiectasis 19,20 Figures 3a, 3b, and 3c. The literature shows that sinusitis, bronchiectasis, and digital clubbing are late complications of PCD that can progress to chronic cor pulmonale and its consequences.
In the present study, the siblings, aged 34 and 37 years, also presented, in addition to the alterations mentioned, quite prominent digital clubbing. None of these malformations were observed in the cases reported here. The treatment was exclusively symptomatic bronchial aspiration and respiratory therapy. In the respiratory tract infections, which are common in these patients, the use of aggressive antibiotic therapy against the most frequently isolated agents Haemophilus influenzae and Streptococcus pneumoniae was essential.
In addition to these measures, immunization against haemophilus and pneumococcal strains is deemed appropriate. The probability of diagnostic suspicion of PCD increases when patients have had chronic respiratory infections since birth and present situs inversus.
Therefore, it is understood that the ideal is to make the diagnosis early in order to prescribe an appropriate palliative treatment, thus preventing permanent sequelae, such as chronic rhinosinusitis and bronchiectasis.
References 1. Afzelius BA, Eliasson R. Male and female infertility problems in the immotile-cilia syndrome. Eur J Respir Dis Suppl. Mutations in the DNAH11 axonemal heavy chain dynein type 11 gene cause one form of situs inversus totalis and most likely primary ciliary dyskinesia. Primary ciliary dyskinesia syndrome associated with abnormal ciliary orientation in infants.
Eur Respir J. Intraoperative diagnosis of primary ciliary dyskinesia. Otolaryngol Head Neck Surg. Brauer MM, Viettro L. Rev Med Urug. Berdon WE, Willi U. Situs inversus, bronchiectasis, and sinusitis and its relation to immotile cilia: history of the diseases and their discoverers-Manes Kartagener and Bjorn Afzelius.
Pediatr Radiol. J Pneumol. Primary ciliary dyskinesia: diagnosis and standards of care. The immotile-cilia syndrome. A congenital ciliary abnormality as an etiologic factor in chronic airway infections and male sterility. N Engl J Med. Sleigh MA. Primary ciliary dyskinesia. Geremek M, Witt M. Primary ciliary dyskinesia: genes, candidate genes and chromosomal regions.
J Appl Genet. J Bras Med. Afzelius BA. A human syndrome caused by immotile cilia. Disorders of ciliary motility. Am J Med Sci. Rubin BK. Immotile cilia syndrome primary ciliary dyskinesia and inflammatory lung disease. Clin Chest Med.
J Pediatr Rio de J.
Discinesia Ciliar Primária
Kazragar Respiratory infections and the inflammatory immune response to the infections can affect ciliary function, inducing secondary ciliary dyskinesia. Genetically Related Allelic Disorders To date, PCD is the only phenotype associated with biallelic pathogenic variants in 31 of the 32 genes discussed in this GeneReview. Mutations in DNAH1, which encodes an inner arm heavy chain dynein, lead to male infertility from multiple morphological abnormalities of the sperm flagella. Definitive diagnosis In order to establish a definitive diagnosis diwquinesia PCD, certain phenotypic characteristics at least three characteristics, typically five or more characteristics should be present: Dynein assembly factor 5, axonemal. Evaluation of Relatives at Risk It is appropriate to evaluate the older and younger sibs of a proband in order to identify as early as possible those who would benefit from initiation of treatment and preventive measures.
Síndrome de disquinesia ciliar
Discinesia Ciliar Primária