Primary vs Secondary Ciliary Dyskinesia
It is getting to be more and more important to understand the distinction between primary and secondary ciliary defects.* Here is a brief overview:
When you Hear PCD, Think Proteins
Primary or inherited defects are the result of genetic mutations that impact the production or expression of specific proteins. In the case of PCD (which includes KS, SI, ciliary aplasia, etc), those proteins are important in building the structure of cilia and flagella. They are also turning out to be very important in regulating organ placement and development. We have yet to discover what other things may be impacted by these proteins. If, because of a genetic mutation, your body can not make or use a protein adequately–EVERY SYSTEM THAT RELIES ON THAT PROTEIN WILL BE AFFECTED. PCD is not “selective.” You won’t have some cilia that work and others that don’t. You either have the functioning protein or you don’t, so it is a global or systemic problem for which there is no fix until we come up with treatments that work at the genetic level–thus the importance of genetic research.
Also, a faulty protein is with you forever so the problems associated with PCD, unlike SCD, are almost always apparent from birth or shortly thereafter. You won’t develop PCD over time–it is with you from day one. Granted, it may take a few months to recognize that the symptoms are not typical, but if your PCD symptoms started when you were an adolescent or only as an adult, you most likely do not have PCD.
Different Ultrastructural Changes
Secondary ciliary dyskinesia mimics PCD in symptoms. There may also be ultrastructural changes in ciliary biopsies in SCD, but these changes are very different and distinct from primary changes and a pathologist familiar with the two conditions will be able to distinguish between them. Every time anyone has a cold, they experience secondary ciliary dyskinesia. Any viral or bacterial insult will damage and/or destroy cilia. Repeated infections resulting in SCD can have the appearance of genetic ciliary dysfunction, but they are not the same. People with SCD can eventually recover fully functional cilia, assuming the underlying infection or condition can be treated adequately–people with PCD can not. Treatments for SCD and PCD may be very similar or even identical, but that does not mean they are the same disorder.
PCD vs. SCD What Difference Does it Make?
So why does it matter? There are several reasons:
1.) The long-term outlook is different. PCD is progressive and, for many, debilitating. If my child had SCD (or I did) and there was the possibility that whatever is causing the condition could be “cured,” I’d want to know that.
2.) PCD is genetic. It runs in families. Telling someone with SCD that they have PCD will give them the mistaken impression that they are at risk of passing on the genetic mutation that causes PCD when they are not.
3.) If someone is sick enough to have symptoms of SCD, it is important to find out what the actual cause is so that it can be treated appropriately. Clearly, something is wrong. If it is mislabeled PCD, then the true problem may never be identified.
4.) New information about the PCD phenotype (physical expression of the protein defect) is coming to light all the time. For instance, recent papers indicate that some of the proteins associated with PCD are also implicated in congenital heart disease. The new recommendation is that all people with PCD have a thorough cardiac evaluation. Because these proteins are not an issue in SCD, this recommendation does not apply to individuals with SCD. People with SCD who have been misdiagnosed with PCD are then put through an expensive, frightening and unnecessary cardiac evaluation.
5.) Millions of dollars are going into defining the “phenotype” of PCD–what the disease looks like and how it responds over time. This effort will be compromised if people who don’t actually have the genetic mutation are included in the data collection.
If You Think You May be Misdiagnosed
It is frustrating for all of us that the diagnostic picture in PCD is so mangled right now. However, the clinical picture of PCD, and the fact that it is a distinct clinical entity that can be distinguished from other conditions like SCD, is getting clearer all the time. Hopefully, this information will start to make its way into clinical practice so patients don’t have to face the frustration of misdiagnosis as often as they do now–and it is very common. The best way to be sure of your diagnosis is to participate in the research program or to contact one of the six PCD clinical centers who have expertise in this area. These centers are also valuable resources for information about collecting, preparing and analyzing ciliary biopsies for centers not affiliated with the PCD studies.
*PCD—Primary Ciliary Dyskinesia (inherited)
SCD—Secondary Ciliary Dyskinesia (acquired)
Michele