primary ciliary dyskinesia

Primary ciliary dyskinesia (PCD) is usually an autosomal recessive genetic condition in which the microscopic organelles (cilia) in the respiratory system have defective function. Ciliary dysfunction prevents the removal of secretions from the lungs, paranasal sinuses, and middle ear. Bacteria and other irritants in the mucosa lead to frequent respiratory infections.

Kartagener syndrome is a type of PCD associated with mirror-image orientation of the heart and other internal organs (situs inversus). Rare cases of X-linked and autosomal dominant inheritance have also been observed. Primary ciliary dyskinesia occurs in approximately 1 in 16,000 to 20,000 births, meaning that Kartagener syndrome occurs in about 1 in 32,000 to 40,000 births.

Symptoms and signs:
The severity of symptoms in primary ciliary dyskinesia varies among affected individuals. Symptoms often begin shortly after birth and may include coughing, vomiting, choking, and pulmonary atelectasis (neonatal respiratory distress). Affected individuals frequently have chronic infections of the sinuses, middle ear, and lungs, as well as chronic cough, excess mucus production, and hearing loss. Recurrent respiratory infections may lead to irreversible scarring and dilation of the bronchi (bronchiectasis) and severe lung damage.

Cilia are also present in the brain ventricles and reproductive system, so ciliary dysfunction can affect other body systems as well. Affected men are usually infertile due to abnormal sperm motility. PCD may also be associated with infertility and ectopic pregnancy in women.

Ciliary movement may also be important for positioning organs in the developing embryo. Approximately 50% of individuals with PCD have Kartagener syndrome, in which internal organs, including the heart, liver, spleen, and intestines, are located on the opposite side of the body (situs inversus totalis). Some individuals with PCD have a condition called heterotaxy (situs ambiguus), in which internal organs are abnormally positioned and may also have abnormal structure. About 12% of patients with PCD have heterotaxy, and a subgroup of these patients has congenital heart defects, which can be severe and life-threatening.

Diagnosis:
Primary ciliary dyskinesia is definitively diagnosed by examination of lung or sinus tissue obtained via biopsy or by genetic testing. Specific structural defects present in these tissues can be detected using electron microscopy. Early diagnosis is important to allow prophylactic treatment to prevent or reduce damage to the respiratory system caused by recurrent infections. Screening of nasal nitric oxide levels (in patients older than 5 years who can cooperate with maneuvers to close the soft palate) is useful for identifying individuals who may have PCD and should proceed to biopsy. Currently, mutations in 44 genes are known to be associated with PCD. These do not account for all cases, so additional PCD-related genes are still being identified. Clinical genetic testing for PCD is available for some of these genes in commercial laboratories, and new genes are regularly added to testing panels.

Primary ciliary dyskinesia (PCD) usually follows an autosomal recessive pattern of inheritance. Recessive genetic disorders occur when an individual inherits the same abnormal gene for a trait from each parent. If an individual receives one normal gene and one disease gene, they become a carrier of the disorder but usually do not show symptoms. The risk that two carrier parents pass on the defective gene and therefore have an affected child is 25% for each pregnancy. The risk of having a child who is also a carrier is 50% for each pregnancy. The chance that a child receives normal genes from both parents and is genetically unaffected is 25%. The risk is the same for males and females.

All individuals carry multiple abnormal genes for different traits. Parents who are close relatives (consanguineous parents) are more likely than unrelated parents to carry the same abnormal gene, which increases the risk of having children with a recessive genetic disorder.

Therapy:
Treatment is symptomatic. Oxygen therapy or inhalers are recommended. Antibiotics, bronchodilators, steroids, and mucolytics are also used in the treatment of PCD. Routine hearing checks are important for young children. Hearing aids may be appropriate for children with hearing impairment, and speech therapy can help with speech difficulties. Lung transplantation is an option for severe lung disease. If congenital heart defects are present, surgery may be indicated.

• Heterotaxy (abnormally positioned internal organs with abnormal structure)
• Congenital heart defects (in ~50% of cases)
• In about 50% of patients, Kartagener syndrome is diagnosed (internal organs on the opposite side of the body)
• Possible cystic fibrosis
• Frequent infections of the ears, sinuses, bronchi, and lungs
• Rarely granulomatosis with polyangiitis (a vasculitis characterized by inflammation of blood vessels, leading to damage of various organ systems, most commonly the respiratory tract and kidneys)
• Gastroesophageal reflux disease (GERD) – a digestive disorder characterized by the backflow (reflux) of stomach or duodenal contents into the esophagus