Most of our information on SAS, including inheritance of the defect,
has come from colony breeding studies on Newfoundland dogs. Information
from this breed is identical to the clinical features observed in other
breeds with SAS, such as Rottweilers and Golden retrievers, and would be
considered relevant to our breed until proven otherwise. The mode of transmission
found in the Newfoundland dog breeding studies suggests an autosomal dominant
gene trait with variable expression or penetrance, with the variability
probably due to modifying gene factors. This makes the true mode of inheritance
complex, and presents a more challenging problem in eliminating the defect
from the population of dogs.
To help understand the complex genetics of SAS, here is a quick genetics primer:
Mendelian genetics describes a simple genetic trait as having a pair of genes (termed "genotype", with each single gene being called an "allele") that dictates the physical expression of the gene. The location of the gene is called the "locus", with multiple sites taking the plural form as "loci". The physical expression of the gene pair is often observable, giving us the traits that we visually see, feel, or hear (the observed traits being called the "phenotype"). What we see as the phenotype may not clearly indicate all the underlying genes that the dog is carrying for the trait, explaining why we sometimes see an inherited trait expressed in offspring of normal parents. With "dominant" gene expression, the dominant allele becomes the observed phenotype irregardless of what the other allele in the pair contains. With "recessive" gene expression, both alleles of the pair must be the recessive gene type for the observed trait to be seen as the phenotype. There are sometimes a hierarchy of allele types, with a relative dominance/recessive "ladder".
With a dominant gene trait that has variable expression, it is generally
understood that the variability may be due to complex gene factors that
exist at other loci (i.e. locations). It is often considered that the variability
comes from multiple genes that modify the expression of a major dominant
gene (or small number of major dominant genes), having a cumulative effect.
Although not yet directly shown in SAS, the more severe the defect, the
more the cumulative affect is. Regardless of the severity of the case,
any affected SAS animal can produce a degree of severity in its offspring
because
of the dominant genetics of the disease.
Subaortic stenosis has been graded in Newfoundlands based on postmortem
exam: Grade 1 is the mildest form, with raised white nodules occurring
in the area under the aortic valve; Grade 2 is intermediate, with a fibrous
ridge occurring that partially encircles the outflow tract; Grade 3 is
the most severe form, with a fibrous band encircling the entire outflow
tract just under the aortic valve, and may also cause changes in the mitral
valve complex. The mildest lesions create the most frustrating problem
for breeders. While 95% of all cardiac defects cause a heart murmur, the
Grade 1 lesion of SAS does not always create enough change in blood flow
to cause a clinically detectable heart murmur. In studies performed on
Newfoundlands, it was found that ausculation (stethosope exam), cardiac
catheterization, and echocardiography (ultrasound), the most technologically
advanced methods to detect and define heart murmurs, failed to reliably
detect some, if not most, of the mildly affected dogs, as determined by
postmortem exam. The Grade 2 lesions are often associated with soft cardiac
murmurs and minimal changes in the pressure gradient across the aortic
valve. The Grade 3 lesions are usually associated with the more severe
clinical signs, including moderate to severe murmurs, exercise intolerance,
syncope (fainting), congestive heart failure, and sudden death. The importance
of this clinical data is clear - while the genetic makeup for SAS may truly
be present in a dog, the actual detection of subaortic stenosis becomes
difficult in mild cases, with definitive diagnosis of the true carrier
depending on postmortem exams. This makes genetic counseling for this genetic
trait fraught with error and leaves breeders frustrated.
Medical therapy for SAS can also be frustrating. For mild cases, therapy
is usually not indicated, as affected dogs are usually asymptomatic and
can live a full and productive life. The only exception would be prophylactic
antibiotics for potential bacterial problems, such as dental procedures,
surgery, and wounds due to the established risk of endocarditis (bacterial
colonization of the heart valves), causing damage to the valves and potentially
worsening the severity of the clinical signs. For moderate to severe cases
of SAS, therapy is limited to medicines aimed at decreasing the clinical
symptoms, such as those associated with congestive heart failure, but the
benefits of the therapy are minimal and many of these dogs may develop
acute heart arrhythmias as a result of heart muscle ischemia and sudden
death.
So, what do breeders do to try to decrease the incidence of subaortic stenosis? First of all, we must realize the limitations of our current diagnostics in recognizing mildly affected dogs, but also realize that most affected animals will be identified in a comprehensive program of screening. Pursuit of such a program of screening and definitively diagnosing heart murmurs coupled with genetic counseling will result in a decrease in the incidence of the defect in a few generations. This includes screening all breeding stock and retaining those free of the defect, and carefully screening all offspring for the defect and eliminating parents which have produced affected offspring. Dr. Don Patterson describes a program for breeders working to decrease the frequency of SAS.
Conservative Program to Screen Dogs for Discrete Subaortic Stenosis (see reference1)
1). Most, but not all, discrete subaortic lesions will produce a murmur, and it is reasonable to use ausculation as the main screening method. Some very mildly affected defects will go undetected, but neither are these likely to be detected by ultrasound or catheterization.
2). Because the lesion develops postnatally, screening should not be begun until 6-8 weeks of age. Pups with murmurs should be examined by more definitive methods, as needed, to make a diagnosis. Moderate to severe subaortic stenosis can be diagnosed by this age. Pups with mild lesions may not be distinguishable from those with innocent flow murmurs.
3). Pups with low grade murmurs and no other evidence of heart disease should be reexamined at 12-14 weeks of age. If the murmur disappears, the pup can be considered clear of clinically significant congenital heart disease. However, if there are close relatives with subaortic stenosis, it is prudent not to use such animals for breeding stock or use them only if their offspring are carefully screened for congenital heart disease. Discontinue breeding such dogs if they produce pups with confirmed subaortic stenosis.
4). Pups with a low grade murmur that persists beyond 12 weeks should
be reexamined by more definitive methods to make an accurate diagnosis.
If echocardiography or cardiac catheterization and angiocardiography are
used, it should be possible to reduce the number of false positives. Pups
that have a persistent murmur consistent with subaortic stenosis, but have
no evidence of a congenital heart defect after further studies can be considered
clear of a clinically significant lesion, but a very mild lesion cannot
be ruled out. Such animals should not be used for breeding unless there
are other compelling reasons for it. If bred, the offspring of such dogs
should be carefully screened for evidence of congenital heart disease and
breeding discontinued if any affected pups are produced.
References:
1. Genes and the Heart: Congenital Heart Disease. Donald F. Patterson DVM, DSc, Diplomate ACVIM; 1991 Academy of Veterinary Cardiology Proceedings, as presented in conjunction with the 58th Annual Meeting of the AAHA and the Ontario Veterianary Medical Association Meeting, April 13-14, 1991, Toronto, Ontario, Canada.
2. The Genetics and Pathology of Discrete Subaortic Stenosis in the Newfoundland Dog. R.L. Pyle VMD, MS, D.F. Patterson DVM, DSc, S. Chacko DVM, PhD, American Heart Journal, Vol. 92, No. 3, pp. 324-334, September 1976.
3. CVT Update: Canine Subvalvular Aortic Stenosis. Linda B. Lehmkuhl and John B. Bonagura, Kirk's Current Veterinary Therapy, Volume XII, 1994.
4. OFA Congenital Heart Disease Registry: General Procedures. Orthopedic Foundation for Animals, 1996.