NORD gratefully acknowledges Michael R. Knowles, MD, Distinguished Professor, Department of Medicine, and Maimoona A. Zariwala, PhD, MSc, FACMG, Research Professor, Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, for their assistance in the preparation of this report.
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 clearance of mucous from the lungs, paranasal sinuses and middle ears. Bacteria and other irritants in the mucous lead to frequent respiratory infections. Kartagener syndrome is a type of PCD associated with a mirror-image orientation of the heart and other internal organs (situs inversus). Rare cases of X-linked and autosomal dominant inheritance have been observed.
The magnitude symptoms of primary ciliary dyskinesia vary in affected individuals. Symptoms often begin shortly after birth and can include coughing, gagging, choking and lung atelectasis (neonatal respiratory distress). Affected individuals often experience chronic sinus, middle ear and lung infections as well as chronic coughing, excess mucus and hearing loss. The recurring respiratory infections can lead to an irreversible scarring and dilatation in the bronchi (bronchiectasis) and severe lung damage.
Cilia are also present in the ventricles of the brain and in the reproductive system so ciliary dysfunction can also affect other body systems. Affected males are typically infertile because movement of sperm (motility) is abnormal. PCD may also be associated with infertility and ectopic pregnancy in females.
Movement of cilia may also be important in organ placement in the developing embryo. Approximately 50% of individuals with PCD have Kartagener syndrome in which the internal organs including the heart, liver, spleen and intestine are 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 have abnormal structure. Approximately, 12% of the PCD patients present with heterotaxy and a subset of those have congenital heart defects that can be serious and life threatening.
Primary ciliary dyskinesia usually follows autosomal recessive genetic inheritance. Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes for a given trait from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.
All individuals carry multiple abnormal genes for various traits. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.
Primary ciliary dyskinesia occurs in approximately 1 in 16,000 to 20,000 births. That translates to the incidence of Kartagener syndrome as 1 in 32,000 to 40,000 births.
Primary ciliary dyskinesia is diagnosed definitively through examination of lung or sinus tissue obtained from a biopsy or through genetic testing. Specific structural defects that are present in these tissues can be detected under an electron microscope. Early diagnosis is important in order to provide prophylactic treatment to prevent or decrease damage to the respiratory system from recurrent infections. Screening for levels of nasal nitric oxide (in patients over 5 years of age who can cooperate with palate closure maneuvers) is helpful to identify individuals who may have PCD and should proceed with a biopsy. Currently, mutations in 44 genes are known to be associated with PCD. These do not account for all cases of PCD and hence more PCD genes are yet to be identified. PCD clinical genetic testing is available for some of the 44 genes associated with PCD by the commercial laboratories and new genes are being added to their panels periodically.
Airway clearance therapy is used to keep the lung tissue healthy for as long as possible. This therapy may include routine washing and suctioning of the sinus cavities and ear canals. Antibiotics, bronchodilators, steroids and mucus thinners (mucolytics) are also used to treat PCD. Routine hearing evaluation is important for young children and speech therapy and hearing aids may appropriate for children with hearing loss and speech problems. Lung transplantation is an option for severe, advanced lung disease. Surgery may be indicated if heart defects are present.
The Genetic Disorders of Mucociliary Clearance Consortium (GDMCC) is a network of eight centers in North America (University of North Carolina at Chapel Hill, Washington University in St. Louis, University of Washington in Seattle, Children’s Hospital Colorado in Aurora, Stanford University in Palo Alto, National Institute for Allergy and Infectious Diseases in Bethesda, The Hospital for Sick Children in Toronto and St. Michael’s Hospital in Toronto ) that are collaborating in the diagnostic testing, genetic studies and clinical trials in patients with disorders of mucociliary clearance including primary ciliary dyskinesia. Contacts for this consortium are as follows:
Cystic Fibrosis/Pulmonary Research & Treatment Center
Marsico Lung Institute
7215 Marsico Hall
Chapel Hill, NC 27599-7248
Email: [email protected]
7222 Marsico Hall
Chapel Hill, NC 27599-7248
Email: [email protected]
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government website.
For information about clinical trials being conducted at the National Institutes of Health (NIH) in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
Some current clinical trials also are posted on the following page on the NORD website:
For information about clinical trials sponsored by private sources, contact:
For information about clinical trials conducted in Europe, contact:
Bartoloni L. Primary Ciliary Dyskinesia. In: The NORD Guide to Rare Disorders, Philadelphia, PA: Lippincott, Williams and Wilkins; 2003:675.
Boon M, Vermeulen FL, Gysemans W, et al. Lung structure-function correlation in patients with primary ciliary dyskinesia.Thorax 2015;70:339-45.
Lobo J, Zariwala MA, Noone PG Primary ciliary dyskinesia. Semin Respir Crit Care Med. 2015;36:169-79.
Werner C, Onnebrink JG, Omran H Diagnosis and management of primary ciliary dyskinesia. Cilia 2015;4:2
Lucas JS, Burgess A, Mitchison HM, et al. Diagnosis and management of primary ciliary dyskinesia. Arch Dis Child. 2014;99:850-6.
Lucas JL, Leigh MW. Diagnosis of primary ciliary dyskinesia: Searching for a gold-standard. Eur Respir. 2014;J 44:1418-22.
Shapiro AJ, Davis SD, Ferkol TF, et al. Laterality defects other than situs inversus totalis in primary ciliary dyskinesia: Insights into situs ambiguus and heterotaxy. Chest 2014;146:1176-86.
Knowles MR, Daniels LA, Davis SD, et al. Primary Ciliary Dyskinesia: Recent advances in diagnostics, genetics, and characterization of clinical disease. Am J Respir Crit Care Med. 2013;188:913-22.
Leigh MW, Hazucha MJ, Chawla KK, et al. Standardizing nasal nitric oxide measurement as a test for primary ciliary dyskinesia. Ann Am Thorac Soc 2013;10:574-81.
Leigh MW, Pittman JE, Carson JL, et al. Clinical and genetic aspects of primary ciliary dyskinesia/Kartagener syndrome. Genet Med. 2009;11(7):473-87.
Kennedy MP, Omran H, Leigh MW, et al. Congenital heart disease and other heterotaxic defects in a large cohort of patients with primary ciliary dyskinesia. Circulation. 2007;115(22):2814-21.
Zariwala MA, Knowles MR, Omran H. Genetic defects in ciliary structure and function. Ann Rev Physiol. 2007; 69: 423-450.
Brueckner M. Heterotaxia, congenital heart disease, and primary ciliary dyskinesia. Circulation. 2007;115(22):2793-5.
Badano JL, Mitsuma N, Beales PL, et al. The ciliopathies: an emerging class of human genetic disorders. Annu Rev Genomis Hum Genet. 2006;7:125-148.
Van’s Gravesande KS, Omran H. Primary ciliary dyskinesia: clinical presentation, diagnosis and genetics. Ann Med. 2005;37:439-49.
Carlen B, Stenram U. Primary ciliary dyskinesia: a review. Ultrastruct Pathol. 2005;29:217-20.
Noone PG Leigh MW Sannuti A, et al. Primary ciliary dyskinesia: diagnostic and phenotypic features. Am J Respir Crit Care Med. 2004;169:459-67.
Afzelius BA. Cilia-related diseases. J Pathol. 2004;204:470-7.
Zariwala MA, Knowles MR, Leigh MW. Primary Ciliary Dyskinesia. 2007 Jan 24 [Updated 2013 Feb 28]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2015. Available from: http://www.ncbi.nlm.nih.gov/books/NBK1122/ Accessed May 19. 2015.
The information in NORD’s Rare Disease Database is for educational purposes only and is not intended to replace the advice of a physician or other qualified medical professional.
The content of the website and databases of the National Organization for Rare Disorders (NORD) is copyrighted and may not be reproduced, copied, downloaded or disseminated, in any way, for any commercial or public purpose, without prior written authorization and approval from NORD. Individuals may print one hard copy of an individual disease for personal use, provided that content is unmodified and includes NORD’s copyright.
National Organization for Rare Disorders (NORD)
55 Kenosia Ave., Danbury CT 06810 • (203)744-0100