Primary Ciliary Dyskinesia (PCD) is a highly heterogeneous syndrome characterized by congenital impairment of mucociliary clearance (MCC). The underlying cause is a defect of cilia in the airways, making them unable to beat normally and move respiratory secretions. This defect also has an impact in sperm flagella, generating living but immotile spermatozoa and making patients infertile.
The most common defects causing this disease are found in any polypeptide within the axoneme of cilia, in proteins present in the ciliary membrane and matrix, or in proteins needed for the proper assembly of cilia. Depending on the component missing or defective, different clinical manifestations may develop, being the symptoms and disease onset dependent on the underlying genetic defect. Some mutations result in abnormal ultrastructure, while others cause abnormal function but preserved structure. Since nodal cilia are also defective in embryos, body asymmetry occurs randomly so that approximately 50 percent of the patients have situs inversus totalis. The mode of inheritance is mainly autosomal recessive.
The Igenomix Primary Ciliary Dyskinesia Precision Panel can be used to make an accurate and directed diagnosis as well as a differential diagnosis ultimately leading to a better management and prognosis of the disease. It provides a comprehensive analysis of the genes involved in this disease using next-generation sequencing (NGS) to fully understand the spectrum of relevant genes involved.
The Igenomix Primary Ciliary Dyskinesia Precision Panel is indicated for those patients with a clinical diagnosis or suspicion presenting with or without the following manifestations:
- Respiratory distress
- Situs inversus
- Frequent otitis media
- Fatigue and headaches
- Decreased fertility or infertility
The clinical utility of this panel is:
- The genetic and molecular confirmation for an accurate clinical diagnosis of a symptomatic patient.
- Early initiation of multidisciplinary treatment including pharmacological treatment in form of mucolytic agents and antibiotics to deal with frequent infections and exacerbations. Daily chest physiotherapy is commonly used to help reduce the microbial load. Surgical intervention in form of bilateral lung transplantation is also an option for patients with end-stage respiratory insufficiency.
- Risk assessment and genetic counselling of asymptomatic family members according to the mode of inheritance.
- Improvement of delineation of genotype-phenotype correlation.
Afzelius B. A. (1976). A human syndrome caused by immotile cilia. Science (New York, N.Y.), 193(4250), 317–319. https://doi.org/10.1126/science.1084576
Noone, P. G., Leigh, M. W., Sannuti, A., Minnix, S. L., Carson, J. L., Hazucha, M., Zariwala, M. A., & Knowles, M. R. (2004). Primary ciliary dyskinesia: diagnostic and phenotypic features. American journal of respiratory and critical care medicine, 169(4), 459–467. https://doi.org/10.1164/rccm.200303-365OC
Kuehni, C. E., Frischer, T., Strippoli, M. P., Maurer, E., Bush, A., Nielsen, K. G., Escribano, A., Lucas, J. S., Yiallouros, P., Omran, H., Eber, E., O’Callaghan, C., Snijders, D., Barbato, A., & ERS Task Force on Primary Ciliary Dyskinesia in Children (2010). Factors influencing age at diagnosis of primary ciliary dyskinesia in European children. The European respiratory journal, 36(6), 1248–1258. https://doi.org/10.1183/09031936.00001010
Leigh, M. W., Ferkol, T. W., Davis, S. D., Lee, H. S., Rosenfeld, M., Dell, S. D., Sagel, S. D., Milla, C., Olivier, K. N., Sullivan, K. M., Zariwala, M. A., Pittman, J. E., Shapiro, A. J., Carson, J. L., Krischer, J., Hazucha, M. J., & Knowles, M. R. (2016). Clinical Features and Associated Likelihood of Primary Ciliary Dyskinesia in Children and Adolescents. Annals of the American Thoracic Society, 13(8), 1305–1313. https://doi.org/10.1513/AnnalsATS.201511-748OC
Ellerman, A., & Bisgaard, H. (1997). Longitudinal study of lung function in a cohort of primary ciliary dyskinesia. The European respiratory journal, 10(10), 2376–2379. https://doi.org/10.1183/09031936.97.10102376
Tkebuchava, T., Niederhäuser, U., Weder, W., von Segesser, L. K., Bauersfeld, U., Felix, H., Lachat, M., & Turina, M. I. (1996). Kartagener’s syndrome: clinical presentation and cardiosurgical aspects. The Annals of thoracic surgery, 62(5), 1474–1479. https://doi.org/10.1016/0003-4975(96)00493-6