Primary Ciliary Dyskinesia

Primary Ciliary Dyskinesia

National Organization for Rare Disorders, Inc.

Important

It is possible that the main title of the report Primary Ciliary Dyskinesia is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.

Synonyms

  • immotile cilia syndrome
  • PCD

Disorder Subdivisions

  • Kartagener syndrome

General Discussion

Primary ciliary dyskinesia (PCD) is an autosomal recessive genetic condition in which the microscopic cells in the respiratory system called cilia do not function normally. Ciliary dysfunction prevents the clearance of mucous from the lungs, paranasal sinuses and 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).

Symptoms

The symptoms of primary ciliary dyskinesia vary greatly in affected individuals. Symptoms often begin shortly after birth and can include coughing, gagging, choking and lung collapse (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 obstruction 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 men are often 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, half of the PCD patients with heterotaxy have congenital heart defects that can be serious and life threatening.

Causes

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.

Affected Populations

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 32,0000 to 40,000 births.

Standard Therapies

Diagnosis

Primary ciliary dyskinesia is diagnosed definitively through examination of lung or sinus tissue obtained from a biopsy. 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. Research is underway to develop a screening test for nasal nitric oxide that would help to identify individuals who may have PCD and should proceed with a biopsy. Research to develop testing for genes responsible for PCD is also underway. Currently, 14 genes are known to be mutated in PCD. These do not account for all cases of PCD and hence more PCD genes are yet to be identified. Two genes, DNAI1 and DNAH5 together account for approximately 38% of cases. Molecular genetic testing by full gene sequencing for all known PCD-causing genes is available.



Treatment

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.

Investigational Therapies

The Genetic Disorders of Mucociliary Clearance Consortium is a network of nine centers in North America (University of North Carolina at Chapel Hill, Washington University in St. Louis, University of Washington in Seattle, University of Colorado in Denver, Stanford University in Palo Alto, National Institute for Allergy and Infectious Diseases in Bethesda, National Jewish Health in Denver, 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:



Beth Godwin

Administrative Assistant

Cystic Fibrosis/Pulmonary Research & Treatment Center

7019 Thurston Bowles Bldg.

CB#7248

Chapel Hill, NC 27599-7248



FAX: 919-966-7524

Email: godwine@med.unc.edu

Susan Minnix, RN, BSN

Research Coordinator

4007 Thurston Bowles Bldg.

CB#7248

Chapel Hill, NC 27599-7248



FAX: 919-843-5309

Email: sminnix@med.unc.edu



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 web site.



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: prpl@cc.nih.gov



For information about clinical trials sponsored by private sources, contact:

www.centerwatch.com

References

TEXTBOOKS

Bartoloni L. Primary Ciliary Dyskinesia. In: The NORD Guide to Rare Disorders, Philadelphia, PA: Lippincott, Williams and Wilkins; 2003:675.



JOURNAL ARTICLES

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 celiopathies: an emerging class of human genetic disorders. Annu Rev Genomis Hum Genet. 2006;7:125-148.



Zariwala MA, Leigh MW, Ceppa F, et al. Mutations of DNAI1 in primary ciliary dyskinesia: evidence of founder effect in a common mutation. Am J Respir Crit Care Med. 2006;174(8):858-66.



Hornef N, Olbrich H, Horvath J, et al. DNAH5 mutations are a common cause of primary ciliary dyskinesia with outer dynein arm defects. Am J Respir Crit Care Med. 2006;174(2):120-6.



Bush A, Ferkol T. Movement: the emerging genetics of primary ciliary dyskinesia. Am J Respir Crit Care Med. 2006;174(2):109-10.



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.

Fliegauf M, Olbrich H, Horvath J, et al. Mislocalization of DNAH5 and DNAH9 in respiratory cells from patients with primary ciliary dyskinesia. Am J Respir Crit Care Med. 2005;171;1343-9.



Chodhari R, Mitchison HM, Meeks M. Cilia, primary ciliary dyskinesia and molecular genetics. Paediat Respir Rev. 2004;5:69-76.



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.



Coren ME, Meeks M, Morrison I, et al. Primary ciliary dyskinesia: age at diagnosis and symptom history. Acta paediatr. 2002;91:667-9.



INTERNET

Zariwala MA, Knowles MR, Leigh MW . (Updated March 8, 2012). Primary Ciliary Dyskinesia In: GeneReviews at GeneTests: Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1997-2012. Available at http://www.genetests.org. Accessed June 1, 2012.

Resources

American Lung Association in Connecticut, East Hartford

45 Ash Street

E. Hartford, CT 06108

USA

Tel: (860)289-5401

Fax: (860)289-5405

Tel: (800)586-4872

Email: info@lungne.org

Internet: http://www.lungne.org



American Lung Association

1301 Pennsylvania Ave NW

Suite 800

Washington, DC 20004

USA

Tel: (202)785-3355

Fax: (202)452-1805

Tel: (800)586-4872

Email: info@lungusa.org

Internet: http://www.lungusa.org



Primary Ciliary Dyskinesia Foundation

10137 Portland Avenue South

Minneapolis, MN 55420

USA

Tel: (612)386-1261

Fax: (952)303-3178

Email: info@pcdfoundation.org

Internet: http://www.pcdfoundation.org



Genetic and Rare Diseases (GARD) Information Center

PO Box 8126

Gaithersburg, MD 20898-8126

Tel: (301)251-4925

Fax: (301)251-4911

Tel: (888)205-2311

TDD: (888)205-3223

Internet: http://rarediseases.info.nih.gov/GARD/



Madisons Foundation

PO Box 241956

Los Angeles, CA 90024

Tel: (310)264-0826

Fax: (310)264-4766

Email: getinfo@madisonsfoundation.org

Internet: http://www.madisonsfoundation.org



British Paediatric Orphan Lung Disease

Email: admin@bpold.co.uk

Internet: http://www.bpold.co.uk



For a Complete Report

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