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Ann Thorac Surg 1996;62:1474-1479
© 1996 The Society of Thoracic Surgeons

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Original Article: General Thoracic

Kartagener's Syndrome: Clinical Presentation and Cardiosurgical Aspects

Clinics for Cardiovascular Surgery, Thoracic Surgery and Pediatric Cardiology, Children's Hospital and ENT Department, University Hospital Zurich, Zurich, Switzerland

Accepted for publication May 16, 1996.

	Abstract

Top Footnotes Abstract Introduction Patients and Methods Results Comment References

 
Background. Long-term observations in patients with Kartagener's syndrome (situs inversus, bronchiectasis, and sinusitis) are rare. The role of additional cardiac malformations and their surgical repair is not well known.

Methods. Nine patients (5 female and 4 male) with Kartagener's syndrome were identified and followed. Four patients had associated cardiac anomalies; 4 underwent total surgical repair at the ages of 4 (2 patients), 7, and 34 years.

Results. The postoperative period was uneventful, and these 4 patients are doing well 7 months and 2, 9, and 19 years after repair. The other patients are being treated with conservative therapy and are in relatively good condition.

Conclusions. This disease can be temporarily benign when treated with antibiotics and physiotherapy. Associated cardiac anomalies seem to be quite common, and such patients need careful cardiologic follow-up. Surgical intervention can be safely performed in patients suffering from Kartagener's syndrome associated with a congenital cardiac malformation and produces good long-term results. Bilateral lung transplantation seems to be the therapy of choice in patients with respiratory insufficiency but without concomitant cardiac anomalies.

	Introduction

Top Footnotes Abstract Introduction Patients and Methods Results Comment References

 
Kartagener's syndrome is a very rare congenital malformation comprising a classic triad of situs inversus, bronchiectasis, and sinusitis [1]. It is a genetic disorder in which ciliary motility is abnormal and mucociliary transport is impaired in organs with such functions. Unlike the usual situs inversus, which generally remains undetected and asymptomatic, Kartagener's syndrome can cause substantial clinical problems, mainly because of the complications of pulmonary infections. Additional cardiac anomalies usually indicate the worst prognosis. Exact morbidity or mortality figures are not known. Here we report surgical therapy of the associated congenital cardiac anomalies.

	Patients and Methods

Top Footnotes Abstract Introduction Patients and Methods Results Comment References

 
We studied 9 patients with Kartagener's syndrome who underwent operation at the Zurich University Hospital or who were hospitalized at the Children's Hospital between 1961 and 1992. Data were compiled from patients' medical histories and follow-up records. In addition, a questionnaire was sent to all patients, their parents, or their family physicians, in that order. Further information was collected by phone if necessary.

Patient 1
The perinatal period in this patient was unremarkable. The diagnosis of Kartagener's syndrome was established when the patient was 2.5 years old during investigation to determine the cause of chronic rhinorrhea. The following course was uneventful. The girl was lost track of at the age of 3 years.

Patient 2
Situs inversus was diagnosed in this girl at the age of 4 years. Starting at 6 years of age, pulmonary problems arose, with pneumonia occurring at least once a year. With consistent inhalation therapy, long-time drainage, and permanent treatment with antibiotics, her general condition improved. In 1995 the patient was hospitalized because of sudden respiratory deterioration resulting from right ventricular decompensation. After further evaluation, which showed progressive global respiratory failure and radiologically confirmed bilateral marked saccular bronchiectasis, she was accepted for lung transplantation. At transplantation, a bilateral thoracosternotomy in the fifth intercostal space (clamshell incision) was performed and extensive pleural adhesions were dissected. The patient had a total situs inversus. There were three lobes on the left side and two on the right. The pulmonary artery originated from the left-sided ventricle and was anterior to the aorta. Because the patient did not tolerate one-lung ventilation, normothermic cardiopulmonary bypass with cannulation of the right groin was instituted. Standard sequential, bilateral lung transplantation was performed, which necessitated technical changes because of the situs inversus: the recipient's main bronchus and pulmonary artery were short on the left side, and a significant size mismatch of the atrial cuffs was observed on the right side. The recipient's atrium was anastomosed to the enlarged orifice of the inferior pulmonary vein. The patient was extubated on the second postoperative day and discharged after 4 weeks, following an uneventful postoperative course.

Patient 3
This girl was born cyanotic. Investigations revealed total situs inversus associated with double-outlet right ventricle, total anomalous pulmonary venous connection, infundibular pulmonary stenosis, ventricular septal defect (VSD), atrial septal defect (ASD), left-sided peripheral pulmonary artery stenosis, and drainage of the inferior vena cava into the superior vena cava via a persistent azygos vein. Because of recurrent infections of the respiratory tract, surgical repair had to be delayed until the patient was 4 years of age, when total repair of the cardiac malformations was performed. This consisted of the connection of pulmonary veins to the left (systemic) atrium (modified Mustard operation), VSD closure, an open commissurotomy of the pulmonary valve, and subtotal resection of the infundibular pulmonary stenosis. The patient was discharged in good condition.

Patient 4
This infant girl was examined in the first days of life because of a heart murmur. A total situs inversus and VSD were detected. When she was 13 years of age, Kartagener's syndrome was diagnosed because of pulmonary manifestations (recurrent bronchitis). The VSD was considered small, and surgical repair was not advised.

Patient 5
This boy was examined shortly after birth because of cyanosis, and the following diagnosis was established: the triad of Kartagener's syndrome as well as a double-outlet right ventricle with transposition of the great arteries, severe infundibular and pulmonary valve stenosis, marked hypoplasia of the vascular tree of the right lung, VSD, and ASD. A Blalock-Taussig shunt was performed on the left side when the patient was 3 months old. Five years later, progressive cyanosis and exertional dyspnea appeared. At operation the right pulmonary artery was found to be hypoplastic, and a modified Blalock-Taussig shunt using a polytetrafluoroethylene graft was made on the right side. Subsequent examinations revealed satisfactory dimensions of the right pulmonary artery. A total repair was performed when the patient was 7 years old: both aortopulmonary shunts were ligated, the ASD was closed directly, and the VSD was closed with a Dacron velour patch through the right-sided ventriculotomy. The pulmonary artery was transected at the bifurcation and closed proximally. The distal pulmonary artery was connected to the right ventricle with an 18-mm Hancock conduit. The patient's perioperative course was uneventful; extubation was possible on the first postoperative day despite massive tracheal secretion.

Patient 6
In early childhood this boy suffered from chronic rhinorrhea. The diagnosis of Kartagener's syndrome without concomitant cardiac malformations was made incidentally when the patient was 9 years old during evaluation because of cranial trauma. Situs inversus totalis was detected at this time.

Patient 7
Shortly after birth this girl had left-sided pneumonia, and situs inversus totalis was diagnosed. After antibiotic treatment the child was discharged from the hospital in satisfactory condition. Subsequently she had to be rehospitalized several times because of recurrent bronchopneumonia and bronchitis. When the patient was 7 months old, a ciliary abnormality was found in a biopsy specimen of the mucous membrane, thus establishing the diagnosis of Kartagener's syndrome.

Patient 8
This boy was born cyanotic. The results of cardiac catheterization established the diagnosis of total situs inversus, pulmonary atresia, ASD, VSD, and transposition of the great arteries. At the age of 2 weeks, the patient underwent a modified Blalock-Taussig shunt procedure on the right side. An additional central aortopulmonary shunt became necessary 13 months later, because of increased cyanosis. Repeated pulmonary infections with asthmatic symptomatology were observed. A total repair was undertaken when the patient was 2 years old: both aortopulmonary shunts were transected and ligated. The VSD was closed with a Dacron velour patch through the incision in the nonsystemic ventricle. The ASD was closed directly. A homograft (20 mm, 7 cm long; Homograft Brüssel Aortic) was interposed between the pulmonary artery and right ventricle.

Patient 9
Thirty minutes after spontaneous birth this boy showed shortness of breath, lack of oxygen, increasing leukocytosis, and an irregular heart rate of between 110 and 140 beats/min. The chest x-ray study showed pneumothorax, and the infant was admitted to the hospital for further observation. Radiologic examination revealed atelectasis of the upper right lobe and situs inversus totalis. Bronchoscopy and biopsy were performed because Kartagener's syndrome was suspected. Electron microscopy showed immobility of the cilia, confirming the diagnosis. A congenital cardiac malformation could not be found. His general condition improved in response to therapy with antibiotics, and the infant was able to be discharged from the hospital.

	Results

Top Footnotes Abstract Introduction Patients and Methods Results Comment References

 
The details for all patients are summarized in Table 1.

Patient 3 underwent heart catheterization 4 years after surgical intervention, when she was 8 years old, and the results were encouraging. During this hospitalization, bronchiectasis (Fig 1) and sinusitis were detected and the diagnosis of Kartagener's syndrome was established. Echocardiography done 19 years after operation showed satisfactory findings, with mild residual stenosis of the pulmonary veins, mild pulmonary valve stenosis, mild tricuspid valve insufficiency, and normal pressure in the pulmonary circulation. Computed tomography revealed bronchiectasis in both inferior lobes and in the middle lobe. The patient performs a vigorous pulmonary toilet, together with physiotherapy and autogenous drainage. Exacerbations of bronchitis are treated with antibiotics, selected on the basis of the findings in gram-stained sputum. Endocarditis prophylaxis is followed strictly. Her pulmonary situation has obviously improved in response to forced respiratory physiotherapy and the application of topical steroids. The patient does not need any cardiac therapy. She leads a normal physical life and works as an employee in a food store.

View larger version (285K): [in this window] [in a new window]   Fig 1. . Radiologic confirmation (A, posteroanterior; B, lateral) of the bronchial alteration. Bronchiectasis is visible in the basal aspect.

Patient 5's postoperative course has been found to be good at regular follow-up intervals. Nine years after operation the boy shows no clinical or radiologic signs of cardiac decompensation. Upon auscultation a persistent grade 4 ejection murmur is heard over the conduit. There is no cardiomegaly and the lungs appear normal on the chest x-ray study. Besides common colds the patient does not otherwise suffer from recurrent infections and needs no regular medication. He is without symptoms when performing normal physical activity and is able to attend school regularly.

Patient 6 is now 15 years old and has a marked productive coughing spell at least once a day. He is well instructed about the way to adequately expectorate and to perform autogenous physiotherapy. Thus he can manage without medical support. Shadows on the sinus and bronchiectasis were detected in the last x-ray study. Auscultation of the heart and lungs has shown unremarkable findings. He attends school, and his intellectual capacity is normal. The boy is physically fit and able to participate in sports.

Computed tomography performed 6 years after establishment of the diagnosis of Kartagener's syndrome in Patient 7 revealed thickening of the bronchial walls and middle lobe atelectasis on the left side with slightly broadened bronchi. Reduced transparency of the sinus maxillaris and ethmoidalis could be seen on the x-ray study. Her general condition in response to regular physiotherapy and bronchodilating therapy is satisfactory. Definite pulmonary infections have not yet occurred.

The recovery of the fourth operated patient (No. 8) was unremarkable. The child was in satisfactory condition when he was discharged from the hospital. One month after the operation, echocardiography showed mild mitral, tricuspid, and pulmonary regurgitation; no pulmonary stenosis; no ASD or VSD leak; and good function of the homograft. Recurring pulmonary infection was noted 4 months after the operation. Biopsy of the mucous membrane revealed ciliary dysmotility. The child's respiratory condition improved in response to antibiotic and inhalation therapy. Hemodynamically he is doing well and needs no medication.

The youngest of our patients (No. 9) takes no medication and has shown normal development. Pulmonary infections are treated intermittently with antibiotics and inhalation therapy as well as pulmonary physiotherapy to prevent bronchiectasis.

	Comment

Top Footnotes Abstract Introduction Patients and Methods Results Comment References

 
The main abnormality of Kartagener's syndrome is immotile cilia, and this is the ultrastructural impairment that produces clinical symptoms. Ciliated epithelium is situated in the airways, brain ventricles, oviducts, and vasa efferentia of the testes. Electromicroscopic analysis of normal cilia has shown their ultrastructure to consist of two central microtubules surrounded by nine pairs of microtubules, and this system shows three types of connections: the dynein arms, the nexin links, and the spokes (Fig 2A). According to Afzelius [3, 4] and Eliasson [5] and their associates, the adenosine triphosphatase within the dynein arms is responsible for the sliding movement of the ciliary microtubules. The electron microscopic studies in our patients showed a loss of the dynein arms (Fig 2B). In one report [6], a patient was described whose respiratory cilia were not functional but whose spermatozoa were motile and showed a normal ultrastructure, including dynein arms. This indicates the existence of two genes that code for slightly different proteins with analogous functions: one of these genes functions in somatic tissue and the other in the male germ tissue.

View larger version (204K): [in this window] [in a new window]   Fig 2. . (A) Cross-section of normal cilium. (B) Transmission electron micrograph of cross-sections of cilia from a patient with Kartagener's syndrome showing the absence of dynein arms and disorganization of the axoneme.

Kartagener's syndrome occurs in 20,000 to 130,000 people [8, 9]. About half of the patients do not have situs inversus. For this reason some authors have proposed the name the immotile cilia syndrome for the disorder [5]. According to Rossman and associates [10], in Kartagener's syndrome many ciliated cells (up to 40%) are motile but the motion is abnormal, and they suggest changing the name of the syndrome from the immotile cilia syndrome to the dyskinetic cilia syndrome.

It is well known that Kartagener's syndrome is genetic in origin and often occurs in several members of one family. One instance is mentioned in the medical literature in which 5 male children of 3 different fathers in one family had the syndrome [11]. We found only 1 case of a patient with this disease who had a sibling, a brother, who suffered from recurrent bronchitis, which can be a symptom of immotile cilia. Bronchiectasis is usually a chronic disease, and symptoms generally appear in the second or third decade of life [5, 12]. The frequency of bronchiectasis in patients with immotile cilia is approximately 30%, and only 1.5% of them show Kartagener's syndrome [13]. This syndrome is considered benign because patients can lead quite normal lives, be professionally active, and reach an advanced age [14]. However, some cases have been reported in the literature in which there has been a sudden deterioration of health. In 2 of our patients, shortness of breath was noticed soon after birth and 1 patient required urgent intubation.

Taiana and associates [15] reported on successful pulmonary operations in a 25-year-old man, consisting of left lower lobectomy, lingulectomy, and anterior segmentectomy of the left upper lobe. Later, in 1961, Mayo and Lexington [16] described successful pulmonary operations in siblings aged 18 and 11 years. The low segments affected by bronchiectasis were resected. In 1992, Miralles and coworkers [17] reported on a heart-lung transplantation performed in a 25-year-old woman with Kartagener's syndrome. She had suffered severe respiratory insufficiency and right ventricular failure after multiple episodes of respiratory infection. Two years later, Graeter [18] and Macchiarini [19] and their associates reported on bilateral lung transplantation performed in patients with end-stage Kartagener's syndrome.

Presumably, progressive worsening of the bronchiectasis and chronic bronchitis lead to heart failure, particularly when there are associated cardiac anomalies. Postoperative respiratory complications may occur in patients with Kartagener's syndrome and occasionally lead to death [20].

Little is known about the clinical course of patients with Kartagener's syndrome and associated cardiac anomalies. From our experience we conclude that an uncomplicated, insignificant VSD combined with Kartagener's syndrome can assume a favorable course without surgical intervention. One of our patients with such a combination is now 24 years old and fully active and, for the time being, does not need an operation. Multiple associated congenital cardiac malformations do, however, necessitate surgical repair. The coexistence of Kartagener's syndrome should not be a contraindication to operation.

Despite the occasional benign course of Kartagener's syndrome (1 patient reached the age of 75 years [21]), the general condition of patients can suddenly deteriorate as a result of global respiratory failure, even despite aggressive physiotherapy and regular administration of antibiotics. Such an occurrence was reported by Graeter and associates [18] and was also noted in 1 of our patients.

An operation should be timed well, and active infection of the respiratory tract excluded. Postoperatively the patients must be treated very carefully, and great effort has to be taken to continue to prevent respiratory infections. This means antibiotic treatment of acute infections and continuous and regular physiotherapy for bronchial toilet.

In conclusion, we report here the successful surgical treatment of congenital cardiac anomalies associated with Kartagener's syndrome, with excellent long-term results. In addition, the third report of successful bilateral lung transplantation is given here.

	Footnotes

Top Footnotes Abstract Introduction Patients and Methods Results Comment References

 
Address reprint requests to Dr Tkebuchava, Clinic for Cardiovascular Surgery, University Hospital, Rämistrasse 100, CH-8091 Zurich, Switzerland.

	References

Top Footnotes Abstract Introduction Patients and Methods Results Comment References

 

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This Article Abstract Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Urs Niederhäuser Walter Weder Mario Lachat Marko I. Turina Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tkebuchava, T. Articles by Turina, M. I. Search for Related Content PubMed PubMed Citation Articles by Tkebuchava, T. Articles by Turina, M. I.