Genetics and Inheritance of Canine Deafness
Dr. George M. Strain, Louisiana State University Comparative
Biomedical Sciences, School of Veterinary Medicine, Baton Rouge, Louisiana
70803
Congenital deafness in dogs (or other animals) can be acquired
[caused by intrauterine infections, ototoxic drugs like gentamicin, liver
disorders, or other toxic exposures before or soon after birth] or inherited.
Inherited deafness can be caused by a gene defect that is autosomal dominant,
recessive, sex-linked, or may involve multiple genes (more on this later).
It is usually impossible to determine the cause of congenital deafness
unless a clear problem has been observed in the breed, or carefully planned
breedings are performed. In this article I will discuss what is currently
known about the genetics of deafness in dogs so that breeders can make
the best informed decisions possible when attempting to reduce or eliminate
deafness.
Congenital deafness has been reported for approximately 80 breeds, with
the list growing at a regular rate (see list of Dog
Breeds with Reported Congenital Deafness); it can potentially appear
in any breed but especially those with white pigmentation. Deafness may
have been long-established in a breed but kept hidden from outsiders to
protect reputations. The disorder is usually associated with pigmentation
patterns, where the presence of white in the hair coat increases the likelihood
of deafness. Two pigmentation genes in particular are often associated
with deafness in dogs: the merle gene (seen in the Collie, Shetland Sheepdog,
Dappled Dachshund, Harlequin Great Dane, American Foxhound, Old English
Sheepdog, and Norwegian Dunkerhound among others) and the piebald gene
(Bull Terrier, Samoyed, Greyhound, Great Pyrenees, Sealyham Terrier, Beagle,
Bulldog, Dalmatian, English Setter). However, not all breeds with these
genes have been reported to be affected. The deafness, which usually develops
in the first few weeks after birth while the ear canal is still closed,
usually results from the degeneration of part of the blood supply to the
cochlea (the stria vascularis). The nerve cells of the cochlea subsequently
die and permanent deafness results. The cause of the vascular degeneration
is not known, but appears to be associated with the absence of pigment
producing cells (melanocytes) in the blood vessels. All of the function
of these cells are not known, but one role is to maintain high potassium
concentrations in the fluid surrounding the hair cells of the cochlea;
these pigment cells are critical for survival of the stria. Deafness in
the Doberman, which is also accompanied by vestibular (balance) disturbance,
results from a different mechanism, where hair cell death is not the result
of degeneration of the stria. Deafness may also occur later in life in
dogs from other causes such as toxicities, infections, or injuries, or
due to aging (presbycusis); these forms of deafness almost never have
a genetic cause in animals and thus do not present a concern in breeding
decisions.
The prevalence of congenital deafness in different breeds is seldom known
because of the limited number of studies (see table on Breed-Specific
Deafness Prevalence In Dogs). In the Dalmatian, where the incidence
is highest, 8% of all dogs in the US are bilaterally deaf and 22% are
unilaterally deaf. In the English Setter, English Cocker Spaniel, Australian
Cattle Dog, and Bull Terrier, where fewer numbers of dogs have been hearing
tested, the incidence appears to be about one third to one half that of
Dalmatians. Unilateral or bilateral deafness is found in 75% of all white
Norwegian Dunkerhounds, but the incidence in normal-color dogs is unknown.
Other breeds with a high incidence are the Catahoula and Australian Shepherd.
The incidence of all types of deafness in the general dog population is
low, reported to be 2.56 to 6.5 cases per 10,000 dogs seen at veterinary
school teaching hospitals, but these data predate the availability of
hearing testing devices and so are much lower that actual values. Recognition
of affected cases is often difficult, because unilaterally deaf dogs appear
to hear normally unless a special test (the brainstem auditory evoked
response, BAER) is performed; facilities to perform the BAER are usually
only available at veterinary schools (see list of BAER
Testers). It should be noted that a unilaterally deaf dog can be as
great a genetic risk for transmission of deafness to its offspring as
is a bilaterally deaf dog.
The method of genetic transmission of deafness in dogs is usually not
known. There are no recognized forms of sex-linked deafness in dogs, although
this does occur in humans. The disorder has been reported to have an autosomal
recessive mechanism in the Rottweiler, Bull Terrier, and Pointer, but
this suggestion is not reliable because the reports were before the availability
of BAER testing and the ability to detect unilaterally deaf dogs. References
usually state that deafness transmission in most other breeds is autosomal
dominant, but this is false, as will be discussed below. Pigment-associated
inherited deafness is not restricted to dogs. Similar defects have been
reported for mice, mink, pigs, horses, cattle, cats, and humans. Deafness
in blue-eyed white cats is common and is known to be passed on as an autosomal
dominant defect. Blue eyes, resulting from an absence of pigment in the
iris, is common with pigment-associated deafness but is not, in and of
itself, an indication of deafness or the presence of a deafness gene;
however, in several breeds dogs (Dalmatian, English Setter, English Cocker
Spaniel, Bull Terrier) with blue eyes are statistically more likely to
be deaf. Waardenburg's syndrome, a human condition, presents with deafness,
a stripe of white in the hair and beard, blue or different colored eyes
(even in blacks and asians), no pigment behind the retina, and minor structural
deformities around the nose and eyes. This is an autosomal dominant disorder
with incomplete penetrance, which means that individuals that inherit
the disorder may not show all components of the syndrome - i.e., they
may not be deaf. Incomplete penetrance of a defect greatly complicates
the determination of mode of inheritance. At present there is no documentation
that incomplete penetrance is a factor in any canine deafness.
In simple Mendelian genetics, each dog carries two copies of each gene,
one from each parent. The possible outcomes of breedings can be demonstrated
with tables showing the genotype of both parents and the possible combinations
in their offspring. If deafness is carried as a theoretical simple autosomal
recessive gene (d), the breeding of two hearing carriers (Dd) (Table
1) will result, on average, in 25% affected dogs (dd), 50% hearing
carriers (Dd), and 25% free of the defect (DD). The breeding of a carrier
to a dog free of the defect (Table 2) will result in
no affected dogs but 50% carriers and 50% free. The breeding of an affected
dog to a carrier (Table 3) will result in 50% affected,
50% carriers, and no free. Finally, the breeding of an affected dog to
a dog free of the defect (Table 4) will result in 100%
carriers and no affected or free.
If instead the deafness is carried as a simple autosomal dominant gene
(D), the breeding of an affected dog (Dd) to a free dog (dd) (Table
3) would result on average in 50% affected and 50% free. Dogs with
the genotype DD would be unlikely to occur unless two deaf dogs had been
bred. All of the above assumes that incomplete penetrance is not acting.
If more than one gene (recessive and/or dominant) is involved in producing
the deafness, the possible combinations become much more complicated.
In humans more than 50 different autosomal recessive or dominant deafness
genes or loci have been identified. The children of two deaf parents with
two different recessive deafness can be unaffected but carry both genes.
If deafness in dogs results from more than one recessive gene, the possible
outcomes of breedings are more numerous and determination of the mechanisms
of transmission will be difficult.
As stated above, deafness is often associated with the merle (dapple)
gene, which produces a mingled or patchwork combination of dark and light
areas. This gene (M) is dominant so that affected dogs (Mm) show the pattern,
which is desirable in many breeds. However, when two dogs with merle are
bred, 25% will end up with the MM genotype (i.e., Table
1). These dogs usually have a solid white coat and blue irises, are
often deaf and/or blind, and are sterile. Breeders of these dogs breeds
know not to breed merle to merle. In this case the deafness is neither
dominant nor recessive, but is linked to a dominant gene that disrupts
pigmentation and secondarily produces deaf dogs.
Genetic transmission of deafness in dogs with the piebald (sp) and extreme
white piebald (sw) pigment genes, such as the Dalmatian, is less clear.
These genes affect the amount and distribution of white areas on the body.
Deafness in Dalmatians does not appear to be autosomal dominant, since
deaf puppies result from hearing parents. It does not appear to be a simple
recessive disorder: we have bred pairs of deaf Dalmatians and obtained
bilaterally hearing and unilaterally hearing puppies, when all should
have been deaf if the disorder was recessive. These findings might be
explained by a multi-gene cause, the presence of two different autosomal
recessive deafness genes, or a syndrome with incomplete penetrance. Further
studies (in progress) will be required to determine the mechanisms. Several
candidate genes known to cause pigment-related deafness in humans or mice
have been eliminated as the possible cause of pigment-associated deafness
in Dalmatians. Whole-genome screens will hopefully identify the cause
in this and other breeds.
Recent studies have shown that deafness in Dobermans, which do not carry
the merle or piebald genes, results from direct loss of cochlear hair
cells without any effects on the stria vascularis. Vestibular (balance)
system signs, including head tilt and circling, are seen, and the deafness
is transmitted by a simple autosomal recessive mechanism. A similar pathology
has been described for the Shropshire Terrier.
So what should breeders do when deafness crops up? The most conservative
approach would be to not breed the affected animal and not repeat the
breeding that produced deafness. It is frequently recommended (i.e. Dalmatian
Club of America) that bilaterally deaf puppies should be euthanized,
since they make poor pets, are difficult to train, are prone to startle
biting, frequently die from misadventure (cars), and require excessive
care. There is considerable controversy on this point, and there is no
question that many people have successfully raised deaf dogs. For every
story of a problem deaf dog there seems to be a story of one that was
successfully raised. Unfortunately, there is no way to predict how a deaf
puppy will turn out. Unilaterally deaf dogs can make good pets but should
not be bred. When deafness is uncommon in a breed, affected dogs should
not be bred, but this does not mean that all related dogs are a risk and
must be retired from breeding. An understanding of simple autosomal recessive
and dominant patterns, as explained above, can allow the breeder to make
better informed decisions and likely avoid future deaf animals without
sacrificing a breeding line that has been shaped over many years. However,
extreme caution must be used when line breeding of dogs related to deaf
dogs, whether the deafness is unilateral or bilateral. To make these decisions
in an informed manner for breeds with known deafness, it is important
that advantage be taken of hearing testing facilities at veterinary schools.
Unilaterally deaf dogs cannot be detected by other means, and these dogs
will pass on their deafness genes.
Tables:
Table 1: Theoretical outcomes of breeding of
two carriers of a recessive deafness gene (d)
| Table 1
|
Dd |
| Dd |
DD |
Dd |
| Dd |
Dd |
Table 2: Theoretical outcomes of breeding a carrier and a dog free of the recessive deafness gene.
| Table 2
|
DD
|
| Dd |
DD |
DD |
| Dd |
Dd |
Table 3:Theoretical outcomes of breeding a carrier
and an affected dog with the recessive deafness gene.
| Table 3
|
Dd
|
| dd |
Dd |
dd |
| Dd |
dd |
Table 4: Theoretical outcomes of breeding an
affected dog and a dog free of the recessive gene.
| Table 4 |
DD
|
| dd |
Dd |
Dd |
| Dd |
Dd |
