Kartagener Syndrome Treatment & Management
- Author: John P Bent, III, MD; Chief Editor: Ryland P Byrd, Jr, MD more...
Kartagener syndrome represents a wide array of patients along the clinical spectrum; accordingly, management must be tailored towards each individual patient. Continuous clinical follow up is one of the best means of providing this type of individualized care.
Maintenance of dwindling pulmonary function is the primary end goal of clinical treatment. Because of the lack of major randomized control trials involving patients with Kartagener syndrome, no firm guidelines exist for management and most of those currently used are modified from prior cystic fibrosis studies.
Barbot et al compiled existing evidence to formulate general clinical recommendations. They include patients having at least biannual clinical visits, which would involve routine spirometry, sputum culture, and, if needed, imaging studies. It was found that antibiotic treatment was effective for exacerbations.
Antibiotics, intravenous or oral and continuous or intermittent, are used to treat upper and lower airway infections. Although prophylactic antibiotics should be used with great caution in this era of emerging antibiotic resistance, children with primary ciliary dyskinesia are especially good candidates for long-term low-dose preventative antibiotics. New studies have supported prophylactic therapy, with gentamicin demonstrating decreased exacerbation frequency.
Obstructive lung disease, if present, should be treated with inhaled bronchodilators and aggressive pulmonary toilet. Mucolytics may be helpful. Anecdotal reports indicate that inhaled antibiotics, oral and inhaled corticosteroids, and recombinant human DNAse have been used, but no large studies support the use of these agents. It has been found that regular bronchodilators, recombinant human deoxyribonuclease (rhDNase), and N -acetylcysteine have not been proven to be effective, but still are used occasionally in attempts at symptomatic relief.
It has been postulated that breaking up mucosal secretions with nebulized hypertonic or normal saline could be effective.
Pulmonary physiotherapy and exercise also have been shown in some studies to improve respiratory quality.
The most common infectious organisms affecting children with primary ciliary dyskinesia are Haemophilus influenza and Staphylococcus aureus. All patients should have the pneumococcal vaccine and a yearly flu vaccine in addition to standard childhood immunizations. Few long-term trials to measure clinical outcomes and statistical efficacy have been conducted for most medical management strategies.
Strippoli et al found a substantial heterogeneity in management of primary ciliary dyskinesia within and between countries and poor concordance with current recommendations, demonstrating a need to standardize management in this patient population.
Patients with Kartagener syndrome ultimately have an inefficient mucociliary clearance, which is used primarily to prevent toxic and irritant substances from remaining within the respiratory tract. Without this mechanism, patients are much more prone to the complications of such toxins. Patients who smoke cigarettes or have persistent exposure to second-hand smoke are much more likely to develop reactive pneumonias and respiratory distress.
Smoking has been found to have multiple deleterious effects on respiratory cilia. Baseline ciliary beat frequency is increased to clear the irritant, but when the system has an underlying dysmotility, this becomes a less effective response.[14, 15] Children exposed to cigarette smoke may develop additional structural defects to nasal mucosa, causing ciliary function to further decline. Additionally, microscopic models have demonstrated that cigarette smoke also can reduce the length of respiratory cilia.
Ultimately, smoking can cause a more rapid deterioration of lung function in patients with Kartagener syndrome, who lack the usual protective mechanisms. Thus, smoking cessation is critical in the Kartagener patient population, as is avoidance of second-hand smoke.
Tympanostomy tubes are required to reduce conductive hearing loss and recurrent infections. Many patients undergo repeated tympanostomy tube insertions, often complicated by chronic suppurative otitis media. Chronic otorrhea may require special measures for aural hygiene, such as regular otomicroscopy, acetic acid irrigations, or culture-guided topical or systemic antibiotic therapy. Because of anticipated long-term middle-ear disease, inserting tympanostomy tubes is the most sensible method of maintaining the myringotomy because the tube can be expected to stay in the tympanic membrane longer than routine grommets.
When sinus disease is refractory to medical management, functional endoscopic sinus surgery leads to transient improvement in upper and lower respiratory tract symptoms. The antiquated procedure of making a nasal antral window underneath the inferior turbinate may have a role in the management of primary ciliary dyskinesia because this procedure relies on gravitational rather than ciliary clearance of mucus.
Lobectomy may have a role in cases of severe bronchiectasis, but this is not specific to patients with Kartagener syndrome. Reports describe patients who have undergone lung transplantation; however, no studies illustrate long-term efficacy and outcomes.
Consultations from an otolaryngologist, geneticist, pulmonologist, social services agent, or obstetrician/gynecologist or urologist/male fertility specialist (infertility) may be indicated.
Activities can be performed as tolerated; however, patients usually experience mild limitations in physical tolerance.
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|Human Gene||Human Chromosomal Location||Chlamydomonas Ortholog||Ciliary Ultrastructure in Subjects with Biallelic Mutations||Presence of Laterality Defects||Percentage of Individual with Biallelic Mutations||MIM No.|
|DNAH5||5p15.2||DHC ?||ODA defect||Yes||15–21% of all PCD, 27–38% of PCD with ODA defects||608644|
|DNAI1||9p21-p13||IC78||ODA defect||Yes||2–9% of all PCD, 4–13% of PCD with ODA defects||244400|
|DNAI2||17q25||IC69||ODA defect||Yes||2% of all PCD, 4% of PCD with ODA defects||612444|
|CCDC114||19q13.32||DC2||ODA defect||Yes||6% of PCD with ODA defects||615038|
|TXNDC3 (NME8)||7p14-p13||LC5||Partial ODA defect (66% cilia defective)||Yes||na||610852|
|DNAAF1 (LRRC50)||16q24.1||ODA7||ODA + IDA defect||Yes||17% of PCD with ODA + IDA defects||613193|
|DNAAF2 (KTU)||14q21.3||PF13||ODA + IDA defect||Yes||12% of PCD with ODA + IDA defects||612517, 612518|
|DNAAF3 (C19ORF51)||19q13.42||PF22||ODA + IDA defect||Yes||na||606763|
|CCDC103||17q21.31||PR46b||ODA + IDA defect||Yes||na||614679|
|HEATR2||7p22.3||Chlre4 gene model 525994 Phytozyme v8.0 gene ID Cre09.g39500.t1||ODA + IDA defect||Yes||na||614864|
|LRRC6||8q24||MOT47||ODA + IDA defect||Yes||11% of PCD with ODA + IDA defects||614930|
|CCDC39||3q26.33||FAP59||IDA defect + axonemal disorganization||Yes||36–65% of PCD with IDA defects + Axonemal disorganization||613798|
|CCDC40||17q25.3||FAP172||IDA defect + axonemal disorganization||Yes||24–54% of PCD with IDA defects + Axonemal disorganization||613808|
|RSPH4A||6q22.1||RSP4, RSP6||Mostly normal, CA defects in small proportion of cilia||No||na||612649|
|RSPH9||6p21.1||RSP9||Mostly normal, CA defects in small proportion of cilia||No||na||612648|
|HYDIN||16q22.2||hydin||Normal, very occasionally CA defects||No||na||610812|
|DNAH11||7p21||DHC ß||Normal||Yes||6% of all PCD, 22% of PCD with normal ultrastructure||603339|
|RPGR||Xp21.1||na||Mixed||No||PCD cosegregates with X-linked Retinitis pigmentosa||300170|
|OFD1||Xq22||OFD1||nd||No||PCD cosegregates with X-linked mental retardation||312610|
|CCDC164 (C2ORF39)||2p23.3||DRC1||Nexin (N-DRC) link missing; axonemal disorganization in small proportion of cilia||No||na||312610|
|CA = central apparatus; IDA = inner dynein arm; MIM = Mendelian Inheritance in Man; na = not available; N-DRC = nexin–dynein regulatory complex; ODA = outer dynein arm; PCD = primary ciliary dyskinesia.|