Congenital Hypothyroidism with Goiter (CHG)
John C. Fyfe, D.V.M., Ph.D. for TheDogPlace.org 2005
Congenital Hypothyroidism With Goiter is a "thyroid problem" but unlike idiopathic, dietary, or environmentally induced thyroid hormone imbalance, there is little breeders can do other than never repeat a Toy Fox Terrier breeding that produced CHG and test any related dogs before breeding.
The information below is provided by Dr. Fyfe. He is no longer with Michigan State University but is associated with a research company. As a breeder and student of real-life genetics, I urge you to read the information, then form your own opinion regarding the necessity of testing your Toy Fox Terriers. If you missed Part 1 about GHG in the Toy Fox Terrier, you should read that first. Testing Cost & Procedure link at end.
Genetic Basis and Cause for CHG
Dr. John C. Fyfe - In a cooperative effort of TFT breeders, veterinarians,
and a canine genetics researcher at the Michigan State University College of
Veterinary Medicine, the genetic basis of congenital hypothyroidism with goiter
(CHG) in Toy Fox Terriers (TFT) has been discovered, and a DNA-based carrier
test is now available. Thyroid hormone is essential for normal development and
metabolism in dogs, especially in the rapid growth period that puppies
experience. Pups affected with CHG are abnormal from just a few days of age.
They do not move around as much as normal pups, and the head may appear large in
comparison to the body. Most have died or were euthanized by 3 weeks of age. If
nursing care is given and they survive as long as 3 weeks, the eyes do not open,
the ear canals remain very small, and the hair coat is abnormally bristly. By
the second week of age, a swelling on the underside of the neck can be felt and
continues to enlarge with time. The swelling may be mistaken for lymph nodes in
making an incorrect diagnosis of puppy strangles. Delay in lengthening of bones
in the legs, spine, and face causes dwarfism. Most all abnormalities are
alleviated by early diagnosis and daily oral administration of thyroid hormone
medication, but this does not stop the goiter from continuing to enlarge and
constricting the airway. Even treated, this is a disfiguring disorder. Many TFT
breeders have been aware for years that pups as described above have been born
occasionally, but until recently few have received a correct diagnosis or
indication that the disorder was inherited. Affected puppies have occurred in
breeding programs across the United States of America and in New Zealand.
Recent studies have demonstrated that the disorder is inherited as a simple
autosomal recessive trait. For a puppy to have CHG, it must received the mutated
copy (allele) of the disease gene from both parents, and male and female
puppies are equally affected. The parents of affected pups show no outward signs
of disease, but they are obligate carriers, by definition. In a breeding
program, both male and female carriers will pass on their mutant alleles to 50%
of all their offspring, on average. When two carriers are inadvertently mated,
on average 25% of the puppies will have CHG. That means that in litters from
such matings, there may be some combination of CHG and normal pups, all
CHG puppies, or all normal puppies. Unidentified carriers in breeding programs
continue to spread the mutant allele throughout the TFT breed.
CHG in TFT is caused by lack of thyroid peroxidase (TPO), an enzyme in the thyroid
gland responsible for adding iodine to a protein called thyroglobulin. A
mutation in the TPO gene prevents production of the enzyme and the consequent
inability to produce thyroid hormones. Identification of the TPO mutation has
allowed design of a laboratory test to detect the mutation in DNA from dog
blood, cheek cells, and frozen semen. DNA isolated from samples is subjected to
a polymerase chain reaction (PCR) to amplify the portion of the TPO gene
harboring the mutation. Normal and mutant alleles are differentiated by their
susceptibility to cutting with a molecular scissors called a restriction enzyme.
Thus, in a DNA sample from a genetically normal TFT all of the PCR product cuts,
but in a carrier only the half of the product amplified from the normal allele
cuts. Therefore, carrier dogs can be positively identified in the laboratory on
the basis of the presence of the mutant allele in their DNA.
This test is offered to TFT breeders through the Laboratory of Comparative
Medical Genetics at Michigan State University in hopes that it will be used to
eliminate CHG from TFT breeding programs. Testing results are given only to the
person submitting the dog’s sample and are kept strictly confidential. For
instructions on submitting samples, please point your internet browser to http://www.msu.edu/unit/mic/facpages/fyfeform.asp or contact Dr. John C. Fyfe by email: firstname.lastname@example.org or at the address below.
After May 20, 2002 our address will be:
Laboratory of Comparative Medical Genetics
2209 Biomedical Physical Sciences
Michigan State University
East Lansing, MI 48824
Part 1 Congenital Hypothyroidism with Goiter (CHG) and Part 3 Info on testing procedure and cost
As editor, I feel compelled to stipulate that as of May 2012, we are unaware of any results of this study. We are trying to determine If any data was released to the Toy Fox Terrier Club or to OFA. We again request the same data from breeders that was provided to Dr. Fyfe. If you KNOW of a Toy Fox
Terrier litter that contained congenital hypothyroidism with goiter (CHG) we ask you to email
the editor. If you request anonymity, we will respect your wishes. The numerical results of this survey will be reported here and to the Toy Fox Terrier Club Of America.
Editors Note: Only one report of suspected Congenital Hypothyroidism With Goiter has been received. Go on
to GHC Testing and Cost...