Primary ciliary dyskinesia

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Primary ciliary dyskinesia is a disorder that is characterized by chronic respiratory tract infections, abnormally positioned internal organs, and difficulties having biological children (decreased fertility). The signs and symptoms of this condition are caused by abnormal cilia and flagella. Cilia are microscopic, finger-like projections that stick out from the surface of cells. Cilia help cells move where they are needed; they also help move substances within the body. Flagella, which are similar to cilia, are tail-like structures that propel sperm cells forward.

Without properly functioning cilia, people with primary ciliary dyskinesia often have problems removing fluid and particles from their airways. Most babies with primary ciliary dyskinesia experience breathing problems at birth (neonatal respiratory distress), which suggests that cilia also play an important role in clearing fetal fluid from the lungs. Children with primary ciliary dyskinesia typically have year-round nasal congestion and a chronic cough beginning in the first year of life. Because affected individuals also have trouble removing bacteria from the respiratory tract, they may experience frequent respiratory tract infections beginning in early childhood. Chronic respiratory tract infections can result in a condition called bronchiectasis, which damages the passages that lead from the windpipe to the lungs (bronchi). Bronchiectasis can cause life-threatening breathing problems.

Another feature of primary ciliary dyskinesia is recurrent ear infections (otitis media), especially in young children. Otitis media can lead to permanent hearing loss if left untreated. These ear infections are likely related to abnormal cilia within the inner ear.

About 40 percent of people with primary ciliary dyskinesia have a mirror-image reversal of their internal organs (situs inversus totalis). For example, the heart is on the right side of the body instead of the left in these individuals. These abnormalities arise early in embryonic development when the differences between the left and right sides of the body are established. Situs inversus totalis does not typically cause additional health problems. When someone with primary ciliary dyskinesia has situs inversus totalis, they are often said to have Kartagener syndrome.

Heterotaxy syndrome (sometimes also called situs ambiguous) is another disorder of organ development that can be associated with primary ciliary dyskinesia. Approximately 9 to 12 percent of people with primary ciliary dyskinesia have heterotaxy syndrome, which is characterized by abnormalities of the heart, liver, intestines, or spleen. These organs may be structurally abnormal or improperly positioned. In addition, affected individuals may lack a spleen (asplenia) or have multiple spleens (polysplenia). Heterotaxy syndrome is also a result of problems establishing the left and right sides of the body during embryonic development. The severity of heterotaxy syndrome varies widely among affected individuals, and people with this condition may have heart abnormalities that can be life-threatening.

Primary ciliary dyskinesia can also cause fertility problems. Vigorous movements of the flagella are necessary to propel the sperm cells forward to the egg cell. Because their sperm do not move properly, males with primary ciliary dyskinesia often have decreased fertility. Decreased fertility also occurs in some affected females and is likely due to abnormal cilia in the fallopian tubes, which impairs the movement of the egg cell from the ovary to the uterus.

In rare cases, individuals with primary ciliary dyskinesia have an accumulation of fluid in the brain (hydrocephalus). Researchers do not fully understand why some people with primary ciliary dyskinesia develop hydrocephalus.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Variants (also called mutations) in one of over 50 different genes can cause primary ciliary dyskinesia. Many of these genes provide instructions for making proteins that form the inner structure of cilia and produce the force needed for cilia to bend. Coordinated back and forth movement of cilia is necessary for the normal functioning of many organs and tissues. The movement of cilia also supports cell transport and helps establish the left-right axis (the imaginary line that separates the left and right sides of the body) during embryonic development.

Many of the variants that cause primary ciliary dyskinesia disrupt the coordinated movement of cilia. Because cilia have many important functions within the body, abnormalities in the structure or function of cilia can cause a variety of signs and symptoms.

Variants in the DNAH5 and DNAH11 genes account for approximately 33 percent of all cases of primary ciliary dyskinesia. These genes provide instructions for producing proteins that are part of a larger group of proteins (a complex) called dynein. Dynein makes up the structures (arms) within the cilia that generate the force needed for cilia to move.

Variants in the CCDC40 gene account for approximately 9 percent of cases of primary ciliary dyskinesia. This gene provides instructions for producing a protein that helps with the proper assembly of dynein arms. This protein also helps assemble a protein complex that regulates the movement of the dynein arms.

Variants in each of the other genes associated with this condition are found in only a small percentage of cases. In 20 to 30 percent of people with primary ciliary dyskinesia, the cause of the disorder is unknown.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

Primary ciliary dyskinesia is typically inherited in an autosomal recessive pattern, which means both copies of the gene in each cell must have a variant to cause the disorder. The parents of an individual with an autosomal recessive condition each carry one copy of the altered gene, but they typically do not show signs and symptoms of the condition.

In some cases, primary ciliary dyskinesia is inherited in an X-linked pattern. A condition is considered to follow an X-linked pattern if the altered gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes in each cell. In males (who have only one X chromosome) a variant in the only copy of the gene in each cell is sufficient to cause the condition. In females (who have two copies of the X chromosome) one altered copy of the gene may or may not cause the features of the condition.

In rare cases, primary ciliary dyskinesia is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most of these cases, the condition is a result of new (de novo) variants in the gene that occur during the formation of reproductive cells (eggs or sperm) in an affected individual's parent or during early embryonic development. These affected individuals typically have no history of the disorder in their family.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

It is estimated that as many as 1 in 7,500 people worldwide have primary ciliary dyskinesia.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Abnormal sperm motility · Frequent (79-30%)

An anomaly of the mobility of ejaculated sperm.

Abnormal sputum · Frequent (79-30%)

Abnormal appearance of material expectorated (coughed up) from the respiratory system and that is composed of mucus but may contain other substances such as pus, blood, microorganisms, and fibrin.

Chronic otitis media · Frequent (79-30%)

Chronic otitis media refers to fluid, swelling, or infection of the middle ear that does not heal and may cause permanent damage to the ear.

Chronic rhinitis · Frequent (79-30%)

Chronic inflammation of the nasal mucosa.

Chronic sinusitis · Frequent (79-30%)

A chronic form of sinusitis.

Nasal congestion · Frequent (79-30%)

Reduced ability to pass air through the nasal cavity often leading to mouth breathing.

Nasal polyposis · Frequent (79-30%)

Polypoidal masses arising mainly from the mucous membranes of the nose and paranasal sinuses. They are freely movable and nontender overgrowths of the mucosa that frequently accompany allergic rhinitis.

Neonatal respiratory distress · Frequent (79-30%)

Respiratory difficulty as newborn.

Other findings in the same source

From: Orphanet

Additional reported features include Productive cough (Frequent (79-30%)); Recurrent otitis media (Frequent (79-30%)); Recurrent sinopulmonary infections (Frequent (79-30%)); Respiratory tract infection (Frequent (79-30%)); Male infertility (Frequent (79-30%)); Abnormal cardiovascular system morphology (Occasional (29-5%)); Abnormal heart morphology (Occasional (29-5%)); Abnormality of the genitourinary system (Occasional (29-5%)); Abnormality of the skeletal system (Occasional (29-5%)); Airway obstruction (Occasional (29-5%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Primary ciliary dyskinesia is Pulmonology, with a pulmonologist / chest physician as the relevant type of clinician. General physician / Family Medicine; paediatrician for children. Referral depends on symptoms.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• What is the likely explanation for the breathing symptoms?
• Would a breathing test or another investigation change management?
• If symptoms worsen, what written action plan should be followed?

Treatment discussions and follow-up

Where the source describes treatments, these are an overview of possible care, not a prescription for an individual. Ask which option applies to the confirmed diagnosis, what benefit is expected, what adverse effects to watch for and how progress will be assessed. Availability, approvals and local practice can differ from the country described in the source.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.