Kartagener Syndrome

Kartagener syndrome is a rare autosomal recessive genetic disorder with a prevalence of 1:32,000, constituting about 50% of the primary ciliary dyskinesias and characterized with a course including the triad of sinusitis, bronchiectasis and situs inversus. It was first described by Siewert in 1904, but Kartagener recognized in 1933 the triad of disorders as a distinct congenital syndrome.

Primary Ciliary Dyskinesia

Approximately one half of patients with primary ciliary dyskinesia have situs inversus and, thus, are classified as having Kartagener syndrome. Primary ciliary dyskinesia is a rare , ciliopathic, autosomal recessive genetic disorder that causes defects in the action of cilia lining the respiratory tract (lower and upper, sinuses, Eustachian tube, middle ear, fallopian tube, and flagellum of sperm cells. More than 35 genes mutations that causing in disorder of ciliary morphology and function, are known to cause primary ciliary dyskinesia.

The phrase "immotile ciliary syndrome" is no longer favored as the cilia do have movement, but are merely inefficient or unsynchronized.

Respiratory epithelial motile cilia, which resemble microscopic "hairs" (although structurally and biologically unrelated to hair), are complex organelles that beat synchronously in the respiratory tract, moving mucus toward the throat. Normally, cilia beat 7 to 22 times per second, and any impairment can result in poor mucociliary clearance, with subsequent upper and lower respiratory infection. Cilia also are involved in nitric oxide production.

Cause

Kartagener syndrome can be caused by changes (mutations) in many different genes. These genes encode proteins that are important to the structure and function of cilia. Cilia are tiny, hair-like structures that are found on the surface of cells in various parts of the body such as the lining of the airway, the reproductive system, and other organs.

The coordinated movement of cilia in wave-like motions is important to the normal functioning of certain organs and tissues throughout the body and ensures the proper placement of organs in the developing embryo. Mutations in these genes cause the cilia to be either immotile (unable to move) or dysmotile (they move incorrectly), which leads to the many signs and symptoms of Kartagener syndrome.

Inheritance

Kartagener syndrome is inherited in an autosomal recessive manner. This means that to be affected, a person must have a mutation in both copies of the responsible gene in each cell. The parents of an affected person usually each carry one mutated copy of the gene and are referred to as carriers. Carriers typically do not show signs or symptoms of the condition. When two carriers of an autosomal recessive condition have children, each child has a 25% (1 in 4) risk to have the condition, a 50% (1 in 2) risk to be a carrier like each of the parents, and a 25% chance to not have the condition and not be a carrier.

Symptoms

Most of the symptoms of Kartagener syndrome result from the inability of the respiratory cilia to function correctly, such as: chronic sinus infection, frequent lung infections, such as pneumonia and bronchitis, bronchiectasis — lung damage from frequent infections and frequent ear infections.

The important symptom that distinguishes Kartagener syndrome from other types of primary ciliary dyskinesia is the positioning of the internal organs on the side opposite from normal (called situs inversus). For example, the heart is on the right side of the chest instead of the left.

Neonatal respiratory distress may occur. Upper respiratory symptoms may include: chronic rhinorrhoea from early childhood, reduced sense of smell and chronic rhinitis. Recurrent otitis media may occur. Chronic obstructive pulmonary disease (COPD), bronchiectasis and recurrent pneumonia may all be components of the syndrome. Male infertility due to immobile spermatozoa and decreased fertility in females may also occur.

Treatment

Medical care for a person with Kartagener syndrome focuses on the prevention of respiratory infections and prompt treatment of any that may occur. Antibiotics can relieve sinusitis, and inhaled medications and respiratory therapy can help if chronic lung disease develops.

Small tubes may be placed through the eardrums to allow infections and fluid to drain out of the middle ear. Adults, especially men, may have difficulty with fertility and may benefit from consulting a fertility specialist. In severe cases, some inpiduals may require a full lung transplant.

In many inpiduals, the number of respiratory infections begins to decrease by about age 20, and as a result, many people with Kartagener syndrome have near-normal adult lives.

Situs Inversus Totalis

Situs Inversus totalis (SIT) is a rare, genetic, developmental defect during embryogenesis characterized by total mirror-image transposition of both thoracic and abdominal viscera across the left-right axis of the body. SIT is an anatomical variation without specific symptomatology that has a polygenic inheritance pattern, without an established direct relation.

It has an estimated incidence of 1 case per 10,000 in the general population, and has a relation female-male of 1.51, without racial predilection. Usually, the diagnosis is incidental.

The condition affects all major structures within the thorax and abdomen. Generally, the organs are simply transposed through the sagittal plane. The heart is located on the right side of the thorax, the stomach and spleen on the right side of the abdomen and the liver and gall bladder on the left side.

The heart's normal right atrium occurs on the left, and the left atrium is on the right. The lung anatomy is reversed, and the left lung has three lobes while the right lung has two lobes. The intestines and other internal structures are also reversed from the normal, and the blood vessels, nerves, and lymphatics are also transposed.

If the heart is swapped to the right side of the thorax, it is known as "situs inversus with dextrocardia" or " SIT ". If the heart remains on the normal left side of the thorax, a much rarer condition (1 in 2,000,000 of the general population), it is known as "situs inversus with levocardia" or "situs inversus incompletus".

Kartagener Syndrome and Appendicitis

Appendicitis is an acute inflammation of the vermiform appendix, most likely due to luminal obstruction by a fecalith and/or lymphoid hyperplasia, among other possibilities. Typically, the patient describes anorexia, acute ill-defined abdominal pain, beginning in the mesogastric region and then moving to the right iliac fossa, associated with fever, nausea, and vomiting.

Since pain located in the left iliac fossa resulting from acute appendicitis is extremely rare, it may be related to congenital abnormalities such as intestinal malrotation or SIT. This symptom may delay the diagnosis, because other possibilities are more likely perticulitis, renal colic, ruptured ovarian cyst, Meckel’s perticulitis, epididymitis, prostatitis, intestinal obstruction, incarcerated hernia, enteritis, pelvic inflammatory disease, and mesenteric ischemia.

A delayed diagnosis increases the risk of complications such as perforation.

Abnormal ciliary motility leads to recurrent paranasal, sinus, and pulmonary infections, as well as to infertility due to impaired sperm motility. Furthermore, poor ciliary motility during embryogenesis predisposes to laterality defects such as SIT or dextrocardia with situs solitus.

Although Kartagener syndrome is rare, health professionals should be aware of its characterization, mainly in patients with a surgical emergency, because of its atypical clinical presentation, which may lead to misdiagnoses. Therefore, appendicitis should be among the differential diagnoses of pain in the left iliac fossa during emergency care. Imaging exams such as CT, ultrasonography, thoracic X-ray, and diagnostic laparoscopy are of paramount importance for the early diagnosis of appendicitis and can help avoid unfavorable outcomes.

Read also: Symptoms of Sinusitis