We're celebrating
40 years!
Last updated:
4/12/2024
Years published: 1988, 1989, 1996, 1999, 2007, 2008, 2012, 2015, 2020, 2024
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 a genetic condition in which the microscopic organelles (cilia) in the respiratory system do not function properly. 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). PCD usually follows autosomal recessive inheritance, but rare cases of X-linked and autosomal dominant inheritance have been observed.
The severity of symptoms of primary ciliary dyskinesia varies in affected individuals. Symptoms often begin shortly after birth and can include coughing, gagging, choking and neonatal respiratory distress (lung atelectasis). 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 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 PCD patients have heterotaxy and a subset of those have congenital heart defects that can be serious and life threatening.
PCD is known to be caused by changes (disease-causing variants) in over 50 genes. This does not account for all cases of PCD, therefore, more PCD genes are yet to be identified.
Primary ciliary dyskinesia usually follows autosomal recessive inheritance. Recessive genetic disorders occur when an individual inherits a disease-causing gene variant from each parent. If an individual receives one normal gene and one disease-causing gene variant, 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 gene variant and have an affected child is 25% with each pregnancy. The risk of having a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents is 25%. The risk is the same for males and females.
Autosomal dominant and X-linked inheritance patterns have been observed in fewer patients.
Dominant genetic disorders occur when only a single copy of a disease-causing gene variant is necessary to cause the disease. The gene variant can be inherited from either parent or can be the result of a new (de novo) changed gene in the affected individual that is not inherited. The risk of passing the gene variant from an affected parent to a child is 50% for each pregnancy. The risk is the same for males and females.
X-linked genetic disorders are conditions caused by a disease-causing gene variant on the X chromosome and mostly affect males. Females who have a disease-causing gene variant on one of their X chromosomes are carriers for that disorder. Carrier females usually do not have symptoms because females have two X chromosomes and only one carries the gene variant. Males have one X chromosome that is inherited from their mother and if a male inherits an X chromosome that contains a disease-causing gene variant, he will develop the disease.
Female carriers of an X-linked disorder have a 25% chance with each pregnancy to have a carrier daughter like themselves, a 25% chance to have a non-carrier daughter, a 25% chance to have a son affected with the disease and a 25% chance to have an unaffected son.
If a male with an X-linked disorder can reproduce, he will pass the gene variant to all his daughters who will be carriers. A male cannot pass an X-linked gene to his sons because males always pass their Y chromosome instead of their X chromosome to male children.
Primary ciliary dyskinesia occurs in approximately 1 in 16,000 to 20,000 births. Only half of primary ciliary dyskinesia results in Kartagener syndrome. Recent studies have estimated the overall global prevalence of primary ciliary dyskinesia to be at least 1 in 7,554 individuals.
Primary ciliary dyskinesia is diagnosed definitively through examination of ciliary ultrastructure of cilia from lung or nose or sinus tissue obtained from a biopsy and/or through genetic testing. Specific structural defects that are present in these tissues can be detected under an electron microscope. Early diagnosis is important to provide 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. Molecular genetic testing is available to look for variants in some of the genes associated with PCD.
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 be 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 McGill University in Montreal) 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:
Kelli Sullivan
Research Coordinator
4206D Mary Ellen Jones Building CB#7578
Chapel Hill, NC 27599-7578
FAX: 919-966-7524
Email: Kelli_Sullivan@med.unc.edu
Nicole Capps
Research Coordinator
4206D Mary Ellen Jones Building CB#7578
Chapel Hill, NC 27599-7578
FAX: 919-962-9786
Email: nicole_capps@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 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: prpl@cc.nih.gov
Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/
For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com
For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/
TEXTBOOKS
Bartoloni L. Primary Ciliary Dyskinesia. In: The NORD Guide to Rare Disorders, Philadelphia, PA: Lippincott, Williams and Wilkins; 2003:675.
JOURNAL ARTICLES
Ringshausen FC, Shapiro AJ, Nielsen KG, et al. Safety and efficacy of the epithelial sodium channel blocker idrevloride in people with primary ciliary dyskinesia (CLEAN-PCD): a multinational, phase 2, randomised, double-blind, placebo-controlled crossover trial. Lancet Respir Med. 2024;12(1):21-33. doi:10.1016/S2213-2600(23)00226-6
Barber AT, Shapiro AJ, Davis SD, et al. Laterality defects in primary ciliary dyskinesia: relationship to ultrastructural defect or genotype. Ann Am Thorac Soc. 2023;20(3):397-405. doi:10.1513/AnnalsATS.202206-487OC
Castillo M, Freire E, Romero VI. Primary ciliary dyskinesia diagnosis and management and its implications in America: a mini review. Front Pediatr. 2023;11:1091173. Published 2023 Sep 8. doi:10.3389/fped.2023.1091173
Kaspy KR, Dell SD, Davis SD, et al. Situs ambiguus Is associated with adverse clinical outcomes in children with primary ciliary dyskinesia. Chest. Published online December 9, 2023. doi:10.1016/j.chest.2023.12.005
Kim S, Li L, Lin FC, et al. Histologic characterization of primary ciliary dyskinesia chronic rhinosinusitis. Int Forum Allergy Rhinol. Published online November 23, 2023. doi:10.1002/alr.23303
Kinghorn B, Rosenfeld M, Sullivan E, et al. Airway disease in children with primary ciliary dyskinesia: impact of ciliary ultrastructure defect and genotype. Ann Am Thorac Soc. 2023;20(4):539-547. doi:10.1513/AnnalsATS.202206-524OC
Newman L, Chopra J, Dossett C, et al. The impact of primary ciliary dyskinesia on female and male fertility: a narrative review. Hum Reprod Update. 2023;29(3):347-367. doi:10.1093/humupd/dmad003
Raidt J, Loges NT, Olbrich H, Wallmeier J, Pennekamp P, Omran H. Primary ciliary dyskinesia. Presse Med. Published online July 27, 2023. doi:10.1016/j.lpm.2023.104171
Zawawi F, Shapiro AJ, Dell S, et al. Otolaryngology manifestations of primary ciliary dyskinesia: a multicenter study. Otolaryngol Head Neck Surg. 2022;166(3):540-547. doi:10.1177/01945998211019320
Shapiro AJ, Kaspy K, Daniels MLA, et al. Autosomal dominant variants in FOXJ1 causing primary ciliary dyskinesia in two patients with obstructive hydrocephalus. Mol Genet Genomic Med. 2021;9(7):e1726. doi:10.1002/mgg3.1726
Wallmeier J, Nielsen KG, Kuehni CE, et al. Motile ciliopathies. Nat Rev Dis Primers. 2020;6(1):77. Published 2020 Sep 17. doi:10.1038/s41572-020-0209-6
Davis SD, Rosenfeld M, Lee HS, et al. Primary ciliary dyskinesia: longitudinal study of lung disease by ultrastructure defect and genotype. Am J Respir Crit Care Med. 2019;199(2):190-198. doi:10.1164/rccm.201803-0548OC
Hannah WB, DeBrosse S, Kinghorn B, et al. The expanding phenotype of OFD1-related disorders: Hemizygous loss-of-function variants in three patients with primary ciliary dyskinesia. Mol Genet Genomic Med. 2019;7(9):e911. doi:10.1002/mgg3.911
Leigh MW, Horani A, Kinghorn B, O’Connor MG, Zariwala MA, Knowles MR. Primary ciliary dyskinesia (PCD): a genetic disorder of motile cilia. Transl Sci Rare Dis. 2019;4(1-2):51-75. doi:10.3233/TRD-190036
Wallmeier J, Frank D, Shoemark A, et al. De novo mutations in FOXJ1 result in a motile ciliopathy with Hydrocephalus and randomization of left/right Body asymmetry. Am J Hum Genet. 2019;105(5):1030-1039. doi:10.1016/j.ajhg.2019.09.022
Shapiro AJ, Davis SD, Polineni D, et al. Diagnosis of primary ciliary dyskinesia. an official American Thoracic Society Clinical Practice Guideline. Am J Respir Crit Care Med. 2018;197(12):e24-e39. doi:10.1164/rccm.201805-0819ST
Lucas JS, Barbato A, Collins SA, et al. European espiratory Society guidelines for the diagnosis of primary ciliary dyskinesia. Eur Respir J. 2017;49(1):1601090. Published 2017 Jan 4. doi:10.1183/13993003.01090-2016
Knowles MR, Zariwala M, Leigh M. Primary ciliary dyskinesia. Clin Chest Med. 2016;37(3):449-461. doi:10.1016/j.ccm.2016.04.008
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.
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.
Zariwala MA, Knowles MR, Omran H. Genetic defects in ciliary structure and function. Ann Rev Physiol. 2007; 69: 423-450.
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.
INTERNET
Zariwala MA, Knowles MR, Leigh MW. Primary Ciliary Dyskinesia. 2007 Jan 24 [Updated 2019 Dec 5]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1122/ Accessed March 27, 2024.
NORD strives to open new assistance programs as funding allows. If we don’t have a program for you now, please continue to check back with us.
NORD and MedicAlert Foundation have teamed up on a new program to provide protection to rare disease patients in emergency situations.
Learn more https://rarediseases.org/patient-assistance-programs/medicalert-assistance-program/Ensuring that patients and caregivers are armed with the tools they need to live their best lives while managing their rare condition is a vital part of NORD’s mission.
Learn more https://rarediseases.org/patient-assistance-programs/rare-disease-educational-support/This first-of-its-kind assistance program is designed for caregivers of a child or adult diagnosed with a rare disorder.
Learn more https://rarediseases.org/patient-assistance-programs/caregiver-respite/