by Lisa Des Camps and Loretta McDonald
This is the first article in a series that addresses the disease found in the Bichon Frise called Primary Ciliary Dyskinesia. The purpose of the series is to bring awareness to breeders so that they can recognize the disease, identify and effectively treat affected puppies and hopefully prevent the disease. Only by eliminating affected dogs from the breeding population and by limiting the breeding of suspected carriers to non-carriers can this goal be accomplished. We also hope the information will lead to interest in breed specific research to identify the mode of inheritance and provide answers to so many questions about the disease. The information presented in this paper was obtained from three published papers, research presented on the Internet and from interviews with the authors and other veterinarians.
Talk to breeders of the Bichon Frise and you’ll hear stories of ‘snorkeling’ puppies. While most puppies are born healthy, there are some that have a rattling, raspy sound coming from their noses. Search further and you’ll hear reports of puppies born with pneumonia, others with a nasal discharge that often turns green or yellow and other forms of respiratory distress.
Naturally, breeders turn to their veterinarians for help. The usual prescribed treatment is a course of antibiotics for a suspected respiratory infection. Fortunately, the drugs usually clear up the symptoms. Unfortunately, the problem is not solved and the symptoms return.
While the puppies tend to outgrow the symptoms of snorkeling, as older dogs they may have recurring episodes of sinus infections, upper respiratory problems and chest infections that are not identified as symptoms of the same malady. Again, the antibiotic regimen targets only the symptoms and not the cause.
Thus, the questions presented are: What is the cause of snorkeling? Does it correct itself over time or do the symptoms only change? Are there other physical affects and problems? And, of course, breeders want to know how they can avoid the ailment all together. This paper explains what the condition is, how it’s diagnosed, its treatment, outcome, and how to prevent it.
Primary Ciliary Dyskinesia, Kartagener Syndrome and Immotile Cilia Syndrome
The search for a diagnosis of what causes a Bichon puppy to snorkel leads in many directions. The condition is found not only in other breeds of dogs but also in other species, including humans. Fortunately for the Bichon, the condition has been accurately diagnosed as Primary Ciliary Dyskinesia (PCD). Unfortunately, the symptoms can dissipate or become less frequent which has led breeders to believe the problem is not serious. This has helped to mask its identification and consequently has contributed to its perpetuation. A basic understanding of the disease is necessary for further discussion.
In 1933, Manes Kartagener first described the three symptoms common to the illness, situs inversus, bronchiectasis and chronic sinusitis, as a distinct congenital syndrome and thus, it was named after him, Kartagener Syndrome (KS). During the next four decades, researchers further discovered that the cilia (the hair-like structures on the mucus membranes lining such areas as the nose and lungs) involved in all these cases were abnormal, poorly mobile and deformed. Thus, in 1977, the descriptive phrase Immotile Cilia Syndrome was used to characterize the same condition.
Four years later, however, it was found that not all the cilia were immotile, they were however, uncoordinated and inefficient, and thus the name Primary Ciliary Dyskinesia (PCD) was coined to describe all ciliary disorders.
A distinction in a case of KS is what is called situs inversus. Situs inversus is when some organs in the body are mirrored left-right, or found on the opposite side of where they’re normally found. A patient with a ciliary disorder and situs inversus is considered as having KS. Kartagener Syndrome is a part of the larger group of disorders, PCD.
The theory why the organs are reversed is that the ciliary movement is abnormal during embryonic development. Approximately one half of patients with PCD has situs inversus and, thus, is classified as having KS. In patients with PCD, organ rotation occurs as a random event; therefore, half the patients have situs inversus (KS) and the other half have normal situs (PCD).
As mentioned, cilia are the hair-like structures on the mucus membranes lining such areas as the nose and lungs. When properly formed, the cilia move in a wave-like fashion to move fluids through the system and protect the respiratory system from inhaled pathogens (infectious agents that cause illness) such as dust, dirt, and microbes. The cilia are also responsible for the transporting these particles out of the lungs. The beating of the cilia transports the fluid upwards until it can be coughed out.
However, when the cilia are deformed both in structure and in the way they are anchored, they cannot move in unison (dyskinesia) so fluids and pathogens collect and become trapped in the airways. The result is chronic respiratory infections leading to bronchitis and pneumonia.
Cilia are also present in the male and female reproductive tracts. The tail of a sperm itself is a very long cilium. A consequence of the deformed cilia in these areas is that it can lead to infertility.
Cilia are also responsible for moving the cerebrospinal fluid in the brain. Consequently, a small proportion of affected Bichons have hydrocephalus. Hydrocephalus is the abnormal buildup of cerebrospinal fluid in the ventricles (cavities) of the brain. The form of hydrocephalus seen in the Bichon does not cause any clinical signs and does not impair the dog’s quality of life.
It is important to note, however, there are forms of PCD in humans that are also associated with hydrocephalus. This observation strengthens the theory that we are truly dealing with PCD in the Bichon and not, as previously thought an immune disease. The Irish Wolfhound study through the University of Pennsylvania further investigated this important distinction.
The study concluded that Irish Wolfhound Rhinitis, or PCD, is not caused by an immune system defect. The main reason Wolfhound Rhinitis was thought to be caused by an immune defect was because, in the past, the immune systems of affected dogs were always examined during phases of severe illness; the immune system is never normal in very sick or dying individuals. For their studies, they treated the affected dogs and waited until they were clinically healthy to examine their immune systems. After an exhaustive examination and comparison of the immune system of affected dogs and their normal littermates they found no differences, thus dispelling the immune system defect.
It is understandable why more cases of PCD are not diagnosed. The usual problems of misdiagnoses are apparent. Newly whelped puppies may be incorrectly diagnosed as ‘fading puppies,’ or as having pneumonia due to inhalation of maternal fluid or having neonatal respiratory virus infection. Furthermore, carriers of PCD may be less fertile and thus produce fewer puppies than unaffected and carrier dogs. Finally, affected puppies may die before birth or shortly thereafter and are thus not seen by a veterinarian. The breeder has no reason to suspect an underlying genetic disease.
The Symptoms and Diagnosis
PCD normally presents itself in the neonatal period or prior to three months of age. As previously discussed, a breeder’s first glimpse of the problem is the puppy that has a rattling, snorkeling sound coming from its nose. It’s a reasonable conclusion for the breeder to suspect the amniotic fluid has not been cleared from the puppy’s airway. There may also be a nasal discharge. It is common for the affected puppies to lay with their heads up the wall of the whelping box after birth in order to catch their breaths.
As the puppies get older, the snorkeling becomes chronic. It may disappear for a few days but will return. As the puppies continue to age, they may become completely symptom-free around the age of one and one half years. Some breeders and owners report the symptoms persist but recur less often and are easier to manage.
The symptoms of the adult dog are harder to recognize. These Bichons have repeated bouts of sinus infections, upper respiratory problems and pneumonia. Antibiotics are generally prescribed but the infections are difficult to treat. It is reasonable to suspect PCD as the cause of these recurring infections.
Recognition of the signs of PCD is the first step in diagnosing the disease. However, only an electron microscope or Gama-ray examination of the suspected cilia can make a firm diagnosis. Moreover, samples cannot be taken from a puppy until it is five weeks old.
In addition to the deformed cilia, a radiographic examination (dorsal- ventral or ventral-dorsal and not lateral) will find about fifty percent of the dogs’ hearts to be on the right instead of the left side of the chest. In some cases, other internal organs may also be transposed.
The male sperm are also adversely affected because the tail of the sperm is formed from cilia. Consequently, the affected males are sub- or infertile with a large number of the sperm being immotile. In bitches, the reproductive organs are likely to be immature.
A radiograph may show evidence of bronchitis, bronchiectasis and bronchopneumonia. These findings are responsible for a large number of misdiagnoses of canine distemper viral infection. Other organs can also be affected by PCD. The dog may develop middle ear infections (otitis media), the kidneys may acquire lesion leading to the need for dialysis or kidney transplantation (renal fibrosis), there may be abnormal bone growth (sternum, vertebrae, and ribs) and, as mentioned earlier, the brain may develop hydrocephalus.
The breeder, scientist and veterinarian look forward to the day when PCD has been eradicated. In that direction, research continues to find the gene mutation that affects the cilia. Despite the advances in science, the process is slow. The dog has a complicated genome with 78 chromosomes. Fortunately, the human genome is widely mapped and is fairly similar to the canine genome.
The mutation is likely to affect one of the proteins present in the cilia. Therefore, if the genes known to be related to ciliary proteins are examined first, only 1 – 200 genes need investigation, not 80,000 – 100,000. The advent of a canine genome map has made this type of research much quicker.
What researches are looking for is a genetic marker, which is a gene or DNA sequence that has a known location on a chromosome and is associated with a particular gene or trait. Genetic markers associated with certain diseases can be detected in the blood and used to determine whether an individual is at risk for developing a disease.
These markers can be used to identify groups of genes, and if an individual inherits a particular marker with a genetic disease, the gene responsible must lie close to the marker on the same chromosome. The nearer a marker lies to the mutated gene, the more likely they are to be inherited together. Once a close marker has been identified, the mutated gene becomes easier to find.
Once the mutated gene responsible for a genetic disease has been identified, a simple, reliable test can be developed which will identify the presence of that gene on an affected individual’s ‘DNA fingerprint’, or in a carrier. This means that a blood sample or cheek swab can identify carriers before they are bred. The disadvantages with this type of DNA test are that it can only be performed in specialist centers and each test is usually specific to only one disease in one breed.
Mode of Inheritance / Breeding
For the breeder, it is most important to know the mode of inheritance in order to avoid producing puppies with PCD. At this time the mode of inheritance is not known. It is currently believed to be Autosomal Recessive as it is in humans and some other breeds of dogs. However more in depth breed specific studies on the Bichon Frise need to be done to be able to accurately state the mode of inheritance. It is thought by some researchers to be based on more than one gene which would not then be a simple autosomal recessive inheritance but a complex mode of inheritance with the major contribution being autosomal recessive. This means that a dog that has PCD has gotten two defective genes: one (or more) from its sire and one (or more) from its dam. Most alarming for the breeder is that the parents show no signs of PCD and are physically healthy. Despite the fact they are healthy, they are in fact carriers of the gene that causes PCD and can pass it on to their get.
Currently, there is no reasonable way to distinguish carriers from normal dogs because they look the same and do not have the disease. To eliminate PCD from the breeding population, a DNA-based test would be extremely valuable, but the marker is not known, and thus no scientific test exists.
At this time, there are only two ways to know if potential parents are carriers. The first scenario is to breed them and wait to see if puppies with PCD are born. The second way is to breed a known carrier of the PCD gene to a suspected non-carrier. If more than 11 normal pups are born, the suspected non-carrier parent is most likely not a carrier. Clearly, this is a crude method of "genetic testing" and is unacceptable to most breeders.
However if there was a PCD affected pup in a litter it can be assumed that approximately 50% of the pup’s litter mates would be carriers of the gene/s.
Long Term Care of an Affected Dog
In general, dogs with this condition can live long and in relative comfort if they are maintained properly and have the right combination of antibiotics. If the symptoms are severe, other treatment may be necessary, such as frequent inhalation of steam. Another effective treatment is ‘coupage,’ patting the affected dog on the side of the chest for several minutes on each side, which helps loosen any mucous that is stuck in the deeper airways, allowing the dog to breathe more easily.
As noted, Bichon puppies may actually improve as they get older. Some are completely symptom free at or around the age of one and a half years. Others have symptoms that are easier to manage but still recur. In either case, proper care is necessary when respiratory ailments are present.
The next article in the series will address how to care for puppies/dogs that have PCD.
Primary Ciliary Dyskinesia in Bichon Frise Litter Mates, Journal of the American Animal Hospital Association, November/December 1991 Vol. 27, Shelly Vaden, DVM, Charles Henrikson, PhD, Michael Metcalf, DVM, Leah Cohn, DVM and William Craig, Jr., MA
Primary Ciliary Dyskinesia in the Dog, Problems in Veterinary Medicine, April-June 1992, Vol 3, No. 2, David Edwawrds, DVM, Clark Patton, MS, DBM, and John Kennedy, PhD
Kartagener’s (Immotile Cilia) Syndrome in Bichon Frise, W. Jean Dodds, DVM, Steven Craft, DVM, Mark Kopit, DVM, Lon Rich, DVM, PhD, Dennis Wilson, DVM, PhD
Wolfhound Rhinitis/Primary Ciliary Dyskinesia, Margret L. Casal, med. vet, PhD
Genome: The ordering of genes in a haploid set of chromosomes of a particular organism
A genome map identifies where particular genes lie on each chromosome.