Madisons Foundation - Moms And Dads In Search Of Needed Support

What

Primary Ciliary Dyskinesia (PCD) is an inherited disorder of defective ciliary movement. Cilia are microscopic, hair-like structures which beat in a coordinated fashion and are present in multiple locations throughout the body. In the respiratory tract, ciliary motion moves mucus secretions, germs, and other debris away from the airways so that they can be swallowed and subsequently excreted.  Without proper ciliary movement, mucus accumulates and attracts additional particles leading to infection, inflammation, and, possibly, permanent widening of the lower airways (bronchiectasis). Additionally, in the developing embryo, these cilia play an important role in organ development.  Human bodies have a "handedness": there are organs that are on the left side and not on the right, and vice versa. During development before birth, the organs of children with PCD may go to the side opposite from normal. This is known as situs inversus.  Kartagener Syndrome (KS) is the combination of situs inversus, bronchiectasis, and sinusitis, all of which is attributable to PCD.  With timely diagnosis and adherence to treatment recommendations, KS patients may have normal lifespan.

Who

KS is usually diagnosed in infancy or early childhood. It can occur in people of all races and is equally present in both sexes. In the United States, the incidence is 1 in 15,000-30,000 births, although the incidence may be higher due to under diagnosis.  KS is a genetic disorder. A child receives two copies of every gene-one from each parent. For a child to be affected by KS, that child must inherit two broken copies of the gene associated with KS. One broken copy must come from the mother and the other from the father. Even though both parents have broken gene copies, they probably are not affected by KS because they each have a second normal copy of the gene. Thus, it is unlikely that the parents could have known that they might have a child with KS. Additionally, parents have no control over whether they give their child a normal or broken copy of a gene. In this scenario in which both parents have one normal gene and one altered gene, each child has a 25% chance of receiving two broken copies and thus having KS. The inheritance pattern just described is known as "autosomal recessive."  There are a few cases of KS which are "X-linked," in which the broken copy of the gene is found only on the X-chromosome.  In these cases, females are protected from the disease because they have two X chromosomes, and if they inherit the broken copy, they will not develop KS.  However, they have a 50% chance of passing the broken copy to their children.  Males who inherit the broken chromosome will have the disease, and will always pass that broken copy to female children, but never to male children.

Signs and Symptoms

The symptoms and severity of KS vary from patient to patient. It is often diagnosed late after a period of generally poor health.  The following list describes features that are associated with KS, but it is important to remember that not all of these apply to every child. 

• 1. Difficulty breathing (respiratory distress), particularly in newborn babies but also in older children;
• 2. Heart on the right rather than the left side of the chest;
• 3. Abdominal organs positioned in the opposite side from normal;
• 4. A cough that produces mucus (productive cough);
• 5. Possible wheezing;
• 6. Repeated bronchitis or pneumonia (respiratory infections) which, over time, can cause damage to the bronchi (lower airways) such that they are permanently expanded. This condition is known as bronchiectasis. Additionally, air entry may be absent in parts of the lung (atelectasis) causing collapses in those portions;
• 7. Frequent and persistent sinus infection with headache;
• 8. Nasal congestion;
• 9. Polyps inside the nose;
• 10. Absent or decreased sense of smell;
• 11. Recurrent ear infections with possible partial hearing loss;
• 12. Infertility in males and decreased fertility in females;
• 13. Clubbing (thickening) of finger or toenails;
• 14. Uncommonly, hydrocephalus or increased pressure in the brain;
• 15. Possible heart defects.

Possible Causes

The genetic alteration in KS causes cilia to move improperly. There are many possible places in the gene for mutations that cause this problem.  While there are several confirmed mutations which can cause KS, not all of them have been discovered.  Ineffective movement is often the result of a detrimental ciliary structure change.  The most serious impairment of ciliary function is decreased mucus movement.  Airway mucus serves a protective role. Its stickiness allows it to trap inhaled germs, dust, and other debris. Cilia then work together in a coordinated fashion to push airway mucus and particles away from the nose and lower airways so that they can be swallowed and excreted.  Ineffective ciliary motion in the upper and lower respiratory tract (nose and airways down through the lungs) leads to accumulation of mucus and its associated debris. Extra mucus obstructs the airways and provides an environment for bacterial overgrowth-leading to cough and respiratory and sinus infections. Over time, repeated infections can weaken particular lung airways known as bronchi and cause them to be permanently dilated. This condition is known as bronchiectasis. With bronchiectasis, infection is more likely, mucus clearing is further impaired, and exhalation becomes difficult. Because cilia are present in a number of other locations throughout the body, KS has additional associated symptoms. Ear infections occur more frequently. Additionally, KS causes defective movement of the cilia-like flagella necessary for sperm motility. Consequently, men with KS are infertile. Female fertility is also reduced as cilia are important for transport of the ovum (egg). However, women with KS can still become pregnant, so birth control is necessary if a woman is not trying to become pregnant. Also, ciliary motion is important for organ movement in the womb, explaining why organs are on opposite sides in KS.

Diagnosis

Diagnosis often occurs later in life because the symptoms of KS (upper respiratory infections) also occur commonly in all children.  Sometimes children with KS are diagnosed because of an associated condition, and sometimes the diagnosis is missed until the patient is having difficulty with infertility as an adult.  The diagnosis of KS is based on a series of tests and studies. Simple tests include measuring the amount of nitrous oxide in exhaled breaths or measuring the time it takes for a patient to taste a sugar tablet placed in the nose.  Chest X-rays may show a heart on the right side of the chest and may reveal thickened airway walls. Sinus X-rays or computed tomography (CT) scans (a special type of photographic-like study) display characteristic changes. A biopsy (sampling of a small piece of tissue) of the nasal passages may be done to study ciliary movement and microscopic structure. Additionally, breathing test to measure lung functions and hearing test are recommended.

Treatment

Treatment is directed at alleviating symptoms and preventing bronchiectasis, lung damage, and other complications. Intervening at an early stage likely improves health later on.  Antibiotics are used to treat bacterial infections. It is important that a patient seek treatment at the start of an infection. Some people, especially those who frequently get respiratory infections, need antibiotics on a more constant basis to prevent future illness or infection. Also, in addition to receiving regular childhood vaccinations, those with KS should be vaccinated against the flu and bacterial pneumonia. Patients also need to use special techniques to rid the airways of excess mucus. These include special body positioning methods (postural drainage), wearing a vibrating vest, or using a special pounding technique on the child's back.  These procedures free mucus from the airways and allow it to be coughed up or swallowed.  Families must use these techniques daily as failure to do so will cause an increased infection rate and lead to bronchiectasis.  Other treatments to alleviate respiratory symptoms include the use of mucolytics to break up mucus and coughing.

Although there is no evidence to support the use of asthma medications for respiratory symptoms in these patients, humidified air may help.  Additionally, individuals with KS should avoid tobacco smoke. Finally, though exercise capacity may be decreased, physical activity is important because it helps release adherent airway mucus.  Jumping and playing blowing games are helpful for young children.  Some patients have good results with machines to provide a constant flow of air into their lungs at night (Positive Expiratory Pressure, or PEP).  To treat frequent ear infections and to minimize hearing loss, ears should be cleaned regularly, kept dry, and sometimes treated with antibiotic eardrops.  For serious cases, ear tubes (tympanostomy tubes) may be surgically placed inside the ears. Some children may need sinus surgery.  Reversed organ position usually does not have complications but provides a clue to the diagnosis.

Prognosis

The prognosis is variable depending upon the timeliness of diagnosis, adherence to physician recommendations, and response to therapy. Obtaining treatment early in the disease course, practicing daily mucus drainage techniques, and seeking prompt treatment for infections may prevent bronchiectasis, decrease lung damage, and thus improve long term prognosis. In late adolescence, children's symptoms often improve, and, barring severe lung or airway damage, many children go on to live productive adult lives. Lifespan may be normal. Additionally, advances in fertilization therapies such as in vitro fertilization may eventually allow men with KS to father children. Women with KS have had children as their fertility is not as affected. Research on KS is currently being carried out to further our understanding of the disease and to develop additional therapies. 

Connect with other parents  In the spirit of community and support, Madisons Foundation offers the unique service of connecting parents of children with rare diseases. If you would like to be connected to other parents of children with this disease, please fill out this brief form.

Connect with other parents

In the spirit of community and support, Madisons Foundation offers the unique service of connecting parents of children with rare diseases. If you would like to be connected to other parents of children with this disease, please fill out this brief form.

Weblinks

The PCD Foundation
http://www.pcdfoundation.org/
Excellent comprehensive website with many resources.

PCD Interest Group
http://www.p-c-d.org/en/
Gives a concise overview of PCD and KS and has an informational brochure with helpful pictures and diagrams.

Medconsumer Info
http://www.medconsumer.info/topics/Kartagener.htm
A helpful list of resources and forums available to patients with PCD and KS.

Google Search for Kartagener Syndrome (KS)
http://www.google.com/search?q=Kartagener+Syndrome+%28KS%29

Google Search for Kartagener Syndrome (KS)

References and Sources

Bent J, Olearczyk M, "Kartagener Syndrome," eMedicine, www.emedicine.com/med/topic1220.htm, 2002.

Bush A, et al. "Primary ciliary dyskinesia: current state of the art." Arch. Dis. Child. 2007;92;1136-1140; originally published online 18 Jul 2007; doi:10.1136/adc.2006.096958

Haddad GG, Chapter 417-"Primary Ciliary Dyskinesia," p. 1327-1328, Behrman: Nelson Textbook of Pediatrics, 16th ed., home.mdconsult.com/das/book/30008127/view/873/1107.html/top, 2000.

Sharma G, "Primary Ciliary Dyskinesia," eMedicine, www.emedicine.com/PED/topic1166.htm, 2002.