Primary Ciliary Dyskinesia - Causes, Symptoms, Diagnosis, and Treatment

What Is Primary Ciliary Dyskinesia?

Primary ciliary dyskinesia is a rare autosomal recessive genetic condition. The respiratory system's microscopic organelles (cilia) have a defective function, and cilia are tiny structures that play a vital role in breathing and reproduction functions. They are tiny finger-like projections that extend from cells. The cilia movement may also play its part in organ placement in the developing embryo. Ciliary dysfunction restricts mucus clearance from the lungs, paranasal sinuses, and middle ears—this prevention of the release of mucus results in the frequent occurrence of respiratory infections. In addition, rarely X-linked and autosomal dominant inheritance has been observed.

Primary ciliary dyskinesia occurs in approximately one in 16,000 to 20,000 births.

What Are the Signs and Symptoms of Ciliary Dyskinesia?

• Neonatal Respiratory Distress - In newborn babies, symptoms begin shortly after birth and can include gagging, coughing, choking, and lung atelectasis (complete or partial collapse of an entire lung).

• Frequent infections in the middle ear, sinus, and lungs are seen.

• Hearing loss and otitis media (middle ear infection in air-filled space behind the eardrum)

• Chronic coughing with excess mucus.

• Bronchiectasis (damage in the bronchi).

• Recurring respiratory infections result in scarring and dilation in the bronchi and severe lung damage.

• Due to the abnormal motility (movement) of sperm, affected males are infertile.

• In females, it is associated with infertility and ectopic pregnancy due to the dysfunction of oviductal cilia.

What Are the Causes of Ciliary Dyskinesia?

• Primary ciliary dyskinesia usually follows autosomal recessive genetic inheritance. The recessive genetic disorder happens when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one for the disease, the person will be a carrier and not associated with any of the symptoms.

• Consanguineous (married within close relatives) parents have a higher chance than unrelated parents of carrying the same abnormal gene, which increases the risk of children having a recessive genetic disorder.

• Patients with primary ciliary dyskinesia (PCD) show approximately 50 % of Kartagener syndrome. The internal organs such as the heart, liver, spleen, and intestine are on the opposite side of the body (situs inversus totalis).

• Some individuals with primary ciliary dyskinesia (PCD), in which the internal organs are abnormally positioned and with abnormal structures, refer to heterotaxy (situs ambiguous).

• Approximately 12 % of PCD patients present with heterotaxy, and some are associated with congenital heart defects that can be serious and life-threatening.

What Is the Pathophysiology of Ciliary Dyskinesia?

Primary ciliary dyskinesia is a genetically inherited disorder. The absence or dysfunction of structures involved in the formation of cilia, including inner and outer dynein (belong to the family of cytoskeletal motor proteins), arms, central apparatus, radial spokes (multi-unit protein structure in axonemes of cilia or flagella), results in the inability of axoneme structures to move. Axoneme refers to the elongated structures that make up cilia and flagella. In the presence of adequate structures, some chemical defects may occur which interfere with ciliary function. In some cases, whatever may be the cause, cilia dysfunction begins and impacts during the embryonic phase of development.

What Are the Related Disorders Associated With Ciliary Dyskinesia?

Symptoms of the following disorders can be similar to those of primary ciliary dyskinesia.

Cystic Fibrosis: Cystic fibrosis refers to a genetic disease that affects approximately 30,000 children and adults in the United States. Due to the defective gene (CFTR), mucus within the lining of the lung's airways is not hydrated properly, which leads to thick, sticky mucus secretions. It clogs the airways, promotes bacterial growth, and results in chronic obstruction, inflammation, and infection of the airways. This thick mucus also obstructs the pancreatic ducts, preventing digestive enzymes from reaching the intestines to help in breaking down and absorbing food.

IgG Deficiency: IgG subclass deficiency manifests with symptoms like recurrent infections of the ears, sinuses, bronchi, and lungs. An IgG is a group of antibodies containing four different IgG molecules. Individuals who are missing or have low levels of one or two types are highly at risk for respiratory infections.

Granulomatosis With Polyangiitis: Granulomatosis with polyangiitis is a rare disorder with inflammation of blood vessels (vasculitis) that damages the respiratory tract and kidneys, including various other organ systems of the body. Symptoms include-

• Chronic middle ear infection (otitis media) resulting in hearing loss.

• Ulceration of the mucous membrane in the nose with secondary bacterial infection associated with sinus pain.

• Persistent runny nose.

• Patients with kidney abnormalities may progress to severe complications like kidney failure.

• If lungs are affected, inflammation of the membranes lining the lungs is associated with cough, and expectoration of blood is observed.

Gastroesophageal Reflux (GERD): Gastroesophageal reflux is a digestive disorder characterized by the flowing back of the stomach's contents or small intestines into the esophagus. Symptoms of gastroesophageal reflux include dysphagia (swallowing difficulties), chest pain, and heartburn or pyrosis (sensation of warmth or burning sensation rising to the neck area).

How Is Ciliary Dyskinesia Diagnosed?

Various diagnostic tests have been carried out. These include-

• Evaluation of Nasal Nitric Oxide Levels: Nitric oxide levels are examined and carried out as a screening test.

• Microscopic Examination: Light microscopic examination of biopsies for evaluating the ciliary beat pattern and frequency.

• Electron Microscopic Analysis of Dynein Arms: This test is considered to be a definitive diagnostic method. The absence of outer dynein arms can be easily identified, whereas the absence of inner dynein arms is difficult to confirm due to the low contrast on electron microscopy. Conventional electron microscopy defines the ultrastructural phenotype of inner dynein arms. Hence, computer-assisted analysis of electron microscopic micrographs is developed to improve inner dynein arm visualization.

• Genetic Evaluation: Genetic testing is a problematic method of testing due to the involvement of multiple genes.

What Are the Treatments for Ciliary Dyskinesia?

• Airway clearance therapy is maintained to keep the lung tissue healthy for as long as possible. It includes routine washing and suctioning of the sinus and ear canals.

• Medications like antibiotics, bronchodilators, steroids, and mucolytics (mucus thinners) are also used to treat ciliary dyskinesia.

• The routine hearing evaluation is done in young children.

• Speech therapy and hearing aids are provided for children with hearing loss and speech problems.

• In case of heart defects, surgery is indicated.

• Lung transplantation is opted for in case of severe or advanced lung diseases.

Conclusion

Primary ciliary dyskinesia is not considered to be life-threatening, but lung and airway diseases can lead to permanent damage. Long-term observation for people with primary ciliary dyskinesia is dependent on the severity of respiratory symptoms. Proper medical history and timely management aid in the better prognosis of this condition.