Toy Fox Terrier Congenital Hypothyroidism (TPO): MSU’s 2003 Discovery

SamOne Toy Fox Terrier pup in our litter just lies there while the others nurse. Slow starter?

Elena MarshMaybe, but a pup that stays still while siblings scramble deserves an early vet visit. A 2003 Michigan State paper described an inherited thyroid disorder that began exactly so.

SamThe parents came from a health-testing breeder. Could an inherited problem still appear?

Elena MarshYes, because carriers look healthy. Check which tests the parents had: OFA’s thyroid registry screens adults for autoimmune disease, not this DNA variant.

SamIf it is a hormone problem, can a pill fix it and give us a normal little dog?

Elena MarshHormone replacement helps, yet the scientist who found the gene wrote that treated pups still do not reach normal weight and stature. That is why breeders test first.

Bottom line: Congenital hypothyroidism with goiter (CHG) in Toy Fox Terriers is an autosomal recessive puppy disorder caused by a nonsense variant in the thyroid peroxidase gene (TPO, c.331C>T), which leaves the thyroid unable to make hormone. Michigan State University researchers described it and launched a carrier test in a 2003 paper. The variant is rare in dogs overall (310 carriers and one affected dog among about 1.05 million mostly American dogs tested in 2019-2021), but 4 of the 48 Toy Fox Terriers in that dataset carried it. Under the OFA’s CHIC program the Toy Fox Terrier must have this DNA test; the Rat Terrier, which carries the same variant, does not. A DNA result is risk information, not a diagnosis: a puppy that grows poorly or develops neck swellings needs a veterinarian, who confirms hypothyroidism with blood tests such as T4, free T4 and TSH. A clear result covers this one variant only.

Puppies that barely moved: what the 2003 Michigan State paper recorded

The disorder entered the veterinary literature through the Journal of Veterinary Internal Medicine in 2003, in a paper by John Fyfe and seven co-authors at the Laboratory of Comparative Medical Genetics, Michigan State University. Their subject was a cluster of Toy Fox Terrier puppies that were wrong from the first days of life. According to the abstract, newborn affected pups were inactive, had an abnormal hair coat, narrow (stenotic) ear canals and delayed eye opening. By one week of age a firm swelling could be felt on each side of the lower neck. Those swellings were the thyroid gland itself, enlarged into a goiter.

Blood work matched the picture: thyroid hormone was low and thyroid-stimulating hormone (TSH) was high. Under the microscope the neck masses showed overgrown follicular cells. At eight weeks the team ran radioiodine uptake and perchlorate discharge studies, which revealed an “organification defect”: the gland was taking up iodide but could not attach it to the protein from which thyroid hormone is built.

Two further observations pointed at a single enzyme. Thyroid tissue from affected pups lacked iodide-oxidising activity, and it lacked a particular form of thyroglobulin that normally appears once iodine has been bound. Both are jobs done by thyroid peroxidase. Sequencing the TPO gene then turned up a nonsense mutation that tracked with the disease through the pedigrees. The pattern of affected and unaffected littermates fitted simple autosomal recessive inheritance.

The final sentences of the abstract are the ones breeders still feel. Oral thyroid hormone replacement “restored near-normal growth and development,” and “a DNA-based carrier test was developed and currently is used by TFT breeders to prevent this disorder.” The diagnosis and the preventive tool arrived together. The full text is paywalled, so the study’s puppy and kennel counts are not quoted here.

SamIf a puppy looks fine at birth, how soon would a breeder see something is wrong?

Elena MarshThe 2003 abstract reports neck swellings palpable by one week; Wisdom Panel’s vet notes place slowed growth at three to eight weeks, often before a pup leaves home.

Iodine with nowhere to go: why a broken peroxidase swells the neck

Thyroid hormone is iodine stitched onto a large carrier protein, thyroglobulin. Thyroid peroxidase is the enzyme that does the stitching. A 2015 paper from the same Michigan State group put the consequence plainly: lack of TPO activity causes failure of iodide incorporation into thyroglobulin, which “leads to unrelenting TSH stimulation” and diffuse overgrowth of the thyroid cells “recognized as goiter.”

The logic is a feedback loop that never closes. The pituitary gland senses too little thyroid hormone and releases more TSH. TSH tells the thyroid to grow and work harder. A gland without a working peroxidase cannot respond with hormone, so it responds with size. That is why this form of congenital hypothyroidism comes with a goiter, and why TSH is high rather than low.

The Toy Fox Terrier variant is a single-letter change, written c.331C>T in the OMIA catalogue of inherited animal disorders, that turns an amino-acid codon into a stop signal. The protein is cut off early. Sources disagree on how to name the affected amino acid, so this article sticks to the DNA notation.

Human medicine knows the same mechanism. A 2010 review from the University of Amsterdam describes inactivating TPO variants as a molecular basis of dyshormonogenesis in people, usually autosomal recessive and usually producing a complete organification defect with severe, permanent hypothyroidism. The dog and the child fail at the same step.

Rare across a million dogs, less rare inside one small breed

The best population data come from genetic screening run by Wisdom Panel. In a 2023 PLOS Genetics study, Donner and colleagues analysed 1,054,293 dogs submitted by owners between November 2019 and August 2021; 93.9% lived in the United States, and most were mixed breeds. The Toy Fox Terrier variant appeared in 310 heterozygous dogs and one homozygous dog. Mixed breeds accounted for 299 of the carriers and for the one affected dog; only 11 carriers were classed as purebred.

The breed table in the supplementary data tells a sharper story. Among the 48 dogs labelled Toy Fox Terrier, the allele frequency was 0.0417, which corresponds to 4 carriers out of 48. That is a small, self-selected group from one consumer test, and “purebred” there meant at least seven of eight great-grandparents from one breed, not registered pedigree. It is not a breed-wide carrier rate. The remaining purebred carriers were scattered across other breeds: four Chihuahuas and single dogs labelled American Staffordshire Terrier, Beagle and Miniature Longhaired Dachshund; no clinical cases have been reported in them.

An earlier cohort points the same way. A 2018 study by the same research group, using Wisdom Health and Genoscoper samples collected from 2005 to 2016, found 40 carriers among 83,183 mixed-breed dogs and 3 among 18,081 purebreds, with no affected dogs. The two cohorts overlap in method but not in samples, and their numbers should not be added together.

Wisdom Panel’s own health page states that the variant is “found in 1 in 5,000 dogs in our testing.” That is a company figure across its whole customer base, with no stated period or denominator, and it does not describe Toy Fox Terriers specifically.

An all-dog average says little about a small breed, where the parents of one litter are what count. A representative carrier frequency for Toy Fox Terriers has not been published.

Traced into Rat Terriers, and a different mutation in Tenterfields

In 2007 a team from the University of California, San Diego, Michigan State and Cornell reported the disorder in Rat Terriers in Veterinary Pathology. Three of five puppies in a litter had stunted growth and neurological abnormalities at nine weeks, with firm symmetrical masses at the thyroid. They were homozygous for a TPO nonsense mutation, and the abstract states that “the same mutation” had previously been described in the Toy Fox Terrier. The dam and a healthy littermate were carriers.

The Rat Terrier paper added something the 2003 report had not covered: the brain. At necropsy, myelin, the insulating sheath around nerve fibres, was visibly deficient, most of all in the corpus callosum that links the two halves of the brain. The authors found that “myelin reduction was paralleled by axon reduction,” suggesting that fewer nerve fibres had formed in the first place. Thyroid hormone is needed for that early wiring, which is why this disorder affects learning and behaviour as well as size.

How did a Toy Fox Terrier variant reach Rat Terriers? The authors pointed to the practice of introducing Toy Fox Terrier bloodlines to breed smaller Rat Terriers, and judged it likely that the mutation crossed over relatively recently. That is an inference, not a traced pedigree. One consumer lab’s page says the variant was “first described in the Rat Terrier”; publication order runs the other way.

The Australian Tenterfield Terrier is a separate story. A 2012 Michigan State study found a different TPO change there, a missense variant in exon 9, in every obligate carrier tested, and in 31% of other clinically normal Tenterfield Terriers. That 31% belongs to Tenterfields only. Spanish Water Dogs (2013) and French Bulldogs (2015) carry yet other TPO variants. Each breed has its own, and a test for one does not read the others.

SamSo a Rat Terrier and a Toy Fox Terrier can share the exact same faulty copy?

Elena MarshYes. The 2007 Rat Terrier paper confirmed the identical TPO mutation and judged it likely came in with Toy Fox Terrier lines used to breed smaller Rat Terriers.

One variant, two parent clubs, opposite CHIC rules

The Canine Health Information Center, run with the Orthopedic Foundation for Animals (OFA), issues a CHIC number to a dog once the tests its parent club has chosen are recorded. For the Toy Fox Terrier, the OFA breed page lists three required items, checked on 12 October 2026: a patellar luxation evaluation, a primary lens luxation DNA test, and a congenital hypothyroidism with goiter DNA test from an approved lab.

The Rat Terrier list, published on the same OFA system, requires cardiac, hip, patella and lens luxation results. CHG is not on it at all. Two clubs, one identical mutation, opposite policies.

OFA’s registry numbers mirror that split. For Toy Fox Terriers, 51 CHG results were on file: 49 clear and 2 carriers, with no affected dogs. For Rat Terriers, 81 results were on file and all 81 were clear. These are only the dogs whose owners chose to register a result, so the figures describe the database, not either breed as a whole. OFA’s trend column shows 77.8% clear among Toy Fox Terriers born from 2021 onward, but the count behind that percentage is small, and it should not be read as a rising carrier rate.

The American Toy Fox Terrier Club’s health page lists CHG among the conditions identified in the breed for which DNA tests exist, and asks buyers to request the parents’ results. It suggests sending results from any lab to OFA and mentions CHIC certification. The club names OFA, Embark, Paw Print Genetics and Wisdom Panel, and says it does not favour one lab over another.

Two “thyroid” boxes can trip up a buyer. The AKC’s Toy Group health-testing table lists the club’s recommended tests for the breed as “Patella Evaluation, Thyroid Evaluation, Primary Lens Luxation (PLL).” Meanwhile the OFA thyroid registry is designed to gather data on autoimmune thyroiditis in adult dogs, using free T4, canine TSH and thyroglobulin autoantibodies, and certifies normal dogs from 12 months of age. Neither of those is the CHG DNA test. A Toy Fox Terrier with an adult thyroid certificate may never have been genotyped for TPO, and a CHG-clear dog can still develop autoimmune thyroid disease later. When reading a pedigree, look for the words “Congenital Hypothyroidism w/Goiter” next to a DNA result.

The breed’s two registries even file it differently. The UKC breed standard (revised January 2024) dates registration under the current name to February 24, 1936, and UKC groups it with terriers; the AKC, where it ranks 108 of 210 breeds, puts it in the Toy Group.

Hormone pills help, but they do not build a normal-sized dog

The research record on treatment is encouraging and sobering at once. The 2003 abstract reports near-normal growth and development with oral thyroid hormone. A 2011 review of congenital hypothyroidism in dogs and cats, published in the New Zealand Veterinary Journal, says adequate replacement “results in a successful outcome in the majority of cases, especially when started early in life.”

Fyfe’s own guidance, written for the Spanish Water Dog Club of America, is more cautious. He writes that most abnormalities are alleviated by early diagnosis at four to eight weeks and daily oral hormone replacement thereafter, “but this will not make the goiter disappear. Even with treatment, CHG pups do not achieve normal weight and stature.” He calls prevention through carrier testing the only reasonable solution. Wisdom Panel’s veterinary notes add that the thyroid may keep expanding despite treatment and could eventually press on the airway.

Case reports in related breeds show what can persist. A French Bulldog described in 2015 became more alert within weeks of starting hormone, yet eight months later still had an abnormal gait, did not respond to sound and struggled with house training. A French Bulldog puppy in a 2024 British report improved in activity, weight and gait within five weeks but kept struggling with house and lead training. Both were diagnosed at seven to nine months, far later than the newborn signs described in Toy Fox Terriers, so they are not a forecast for every case, but they show the brain effects are not always reversible.

Treatment is lifelong, and dose and monitoring belong to the treating veterinarian. No study has followed treated Toy Fox Terriers to report lifespan or long-term cognition.

Human medicine shows what prevention at scale can look like. Newborn screening for congenital hypothyroidism began in Canada in 1974, according to a 2025 review in the European Thyroid Journal, and North America is among the regions the review credits with efficient programmes and adequate coverage. A 2021 European consensus puts primary congenital hypothyroidism at roughly 1 in 2,000 to 1 in 3,000 births. Puppies have no equivalent heel-prick test. For dogs, the screening step has to happen earlier, at the parents.

SamIf treatment works fairly well, why must CHIC-certified Toy Fox Terriers be DNA-tested?

Elena MarshBecause treated pups still fall short: Fyfe wrote that even early-treated CHG pups miss normal weight and stature, and the goiter stays. Clear-to-carrier matings avoid that.

Small, slow or swollen-necked is not always TPO

Most hypothyroid dogs are adults with an acquired disease, and that is a different illness. A 2007 review in Veterinary Clinics of North America states that most cases “result from irreversible acquired thyroid pathologic changes,” with at least half of primary thyroid failure caused by immune-mediated (lymphocytic) thyroiditis. A 2022 VetCompass study of 905,553 dogs in UK primary-care practices found an annual prevalence of 0.23%, with a median age at new diagnosis of 7.65 years. That adult form is influenced by immune genes and other loci, and a TPO test says nothing about it. According to OMIA, citing the 2011 review, only 3.6% of hypothyroid dogs are under a year old.

Within the puppy group, other causes exist:

• A 2018 study of a Shih Tzu family found congenital goiter caused by a sodium/iodide symporter gene (SLC5A5); the authors found no TPO variant in the affected dog.
• In 2026, researchers described Rottweiler dwarfs with a thyroglobulin (TG) variant and no goiter.
• A 1991 report of a Giant Schnauzer family described congenital hypothyroid dwarfism of pituitary or hypothalamic origin, not of thyroid origin.
• A 2001 Argentine study linked excess iodine in some commercial puppy diets to reduced thyroid function in puppies.

One widely used reference adds confusion. The Merck Veterinary Manual lists Toy Fox Terriers among breeds with congenital secondary, that is pituitary, hypothyroidism. The peer-reviewed Toy Fox Terrier work describes a primary thyroid defect with high TSH. If a vet mentions both, the published genetics favour the thyroid explanation for this variant.

For a Toy Fox Terrier puppy, the warning signs in the research are concrete: a pup that is inactive compared with littermates, eyes and ear canals that open late, a coat that looks wrong, swellings on both sides of the neck, and growth that stalls while littermates surge ahead. Wisdom Panel’s notes also describe disproportionate dwarfism with a broad head, a short thick neck and short legs. Any of these is a reason to see a vet promptly, whatever the parents’ results.

Panels, single-gene labs and the cost of reading c.331C>T

The variant appears on all three large US consumer panels. Prices below were displayed on 12 October 2026, without sales tax, and sale prices change often.

• Embark: its condition page covers the Rat, Toy and Hairless Terrier TPO variant and tags it “Provisional” without explaining the label. Breed + Health was $129 on sale (regular $159); Embark for Breeders was $139.
• Wisdom Panel Premium: includes the variant; $127.99 on sale (regular $159.99), results within 3 weeks.
• Orivet: the Toy Fox Terrier Full Breed Profile lists “Congenital Hypothyroidism with Goiter (Toy Fox Terrier Type)” alongside lens luxation and other conditions, at $139.00 with free shipping. Paw Print Genetics test pages now show a merger notice with Orivet.
• Genomia (Czech Republic): a single-variant test for Rat and Toy Fox Terriers at $56.00 excluding VAT, usually 12 business days plus international mail time from the US.

OFA’s own laboratory, run with the University of Missouri, does not offer CHG. OFA’s DNA-test matrix lists Betagene, Embark, HealthGene (Canada), Helica, MyDogDNA, Orivet and Wisdom Health, for CHG in this breed, with a note that OFA cannot guarantee the matrix is current. If CHIC is the goal, confirm with the lab that its result will be accepted, then register it with OFA; the fee for recording an outside DNA result is $15 per test. Michigan State’s laboratory pages could not be checked, so its current offer and price for Toy Fox Terriers are unconfirmed.

What a result means:

• Clear (two normal copies): this variant is absent. It does not exclude other variants, other genes or acquired thyroid disease. One European lab states it outright: the test “excludes only tested mutation but not possible unknown mutations.”
• Carrier (one copy): carriers are described as healthy in the research. Mated to a clear dog, no puppy will be affected by this variant, though about half may be carriers; testing the litter is the usual follow-up.
• Affected (two copies): a reason for prompt veterinary assessment, even in a puppy that seems fine. Two carriers mated together are expected to produce affected puppies about one time in four.

From whelping box to blood test, then the paperwork of a sick puppy

In the United States the first stop is the regular veterinarian, who examines the neck and orders thyroid blood tests. To give a sense of laboratory pricing, the University of Missouri diagnostic lab lists a canine Thyroid Panel 2 (free T4, total T4 and TSH) at $69 and total T4 alone at $30, as fees charged to the submitting clinic, not the owner’s final bill. Puppies with stunted growth or a goiter may be referred to a board-certified small animal internist (ACVIM). A DNA result already in hand can save time; bring the report.

Insurance timing is the hard part, because signs can appear before a puppy is even sold. Embrace covers hereditary and congenital conditions “when not pre-existing at the time of enrollment,” and counts as pre-existing anything noted by the owner or vet before the waiting period ends. Figo also covers inherited illness that is not pre-existing. Embrace offers prescription-drug cover as an option, which matters for a lifelong medicine.

Some states give buyers a remedy. Under Florida Statutes § 828.29, if a licensed vet certifies within one year of sale that a dog is unfit for purchase due to a congenital or hereditary disorder, the buyer may be entitled to a refund, an exchange or vet costs; this applies to breeders selling more than two litters or 20 animals a year, and buyers can sign a waiver. New York’s General Business Law § 753 uses a 180-day window and the term “congenital malformation.” Whether a treated CHG puppy qualifies is a matter for veterinary certification.

UK readers face a different landscape. Neither the Toy Fox Terrier nor the Rat Terrier appears on the Royal Kennel Club’s breed list, so there is no Kennel Club DNA-scheme recording for them. LABOKLIN UK’s CHG test (8434) costs £48.00 including VAT, with a 2-3 week turnaround, but its breed list names Rat Terrier and not Toy Fox Terrier, so ask the lab first; Wisdom Panel Premium costs £144.99. Petplan says it covers hereditary and congenital conditions that had not shown symptoms before the policy started (check the policy wording), and Agria treats them as pre-existing if signs appeared earlier. In England, licensing rules under SI 2018/486 (which apply to anyone breeding three or more litters a year or advertising puppies as a business) state that no dog may be kept for breeding if, on the basis of its genotype, breeding from it could harm its offspring’s health. It does not name CHG, but a known carrier-to-carrier mating is the kind of risk it describes.

Frequently asked questions

Q. How common is CHG in Toy Fox Terriers?
No representative figure exists. In 2019-2021 consumer testing of mostly American dogs, 4 of 48 Toy Fox Terriers carried the variant, and OFA’s registry showed 2 carriers among 51 recorded dogs. Both are small, self-selected groups.

Q. My puppy’s DNA test came back clear. Can it still become hypothyroid?
Yes. The test reads one variant. Adult autoimmune thyroiditis, other genes and non-genetic causes remain possible, so a vet should check any dog with thyroid-type signs.

Q. Is the AKC “Thyroid Evaluation” the same as the CHG test?
Not necessarily. OFA’s thyroid registry screens adults for autoimmune thyroiditis from 12 months. The CHG DNA test is separate and can be done at any age.

Q. Can a CHG puppy live a normal life on hormone treatment?
Treatment improves most signs when started early, but the gene’s discoverer wrote that treated pups do not reach normal weight and stature, and the goiter persists. Treatment is lifelong; your vet decides dose and monitoring.

Q. Do Rat Terriers need this test too?
They carry the same variant, but the Rat Terrier CHIC list does not require it. Breeders using Toy Fox Terrier lines may still choose to test.

Q. Who confirms the diagnosis?
A veterinarian, using examination and blood tests such as T4, free T4 and TSH. A DNA result supports the picture but is risk information, not a diagnosis.

References

• Fyfe JC, Kampschmidt K, Dang V, Poteet BA, He Q, Lowrie C, Graham PA, Fetro VM (2003). Congenital hypothyroidism with goiter in toy fox terriers. J Vet Intern Med 17(1):50-57.
• Pettigrew R, Fyfe JC, Gregory BL, Lipsitz D, Delahunta A, Summers BA, Shelton GD (2007). CNS hypomyelination in Rat Terrier dogs with congenital goiter and a mutation in the thyroid peroxidase gene. Vet Pathol 44(1):50-56.
• Dodgson SE, Day R, Fyfe JC (2012). Congenital hypothyroidism with goiter in Tenterfield terriers. J Vet Intern Med 26(6):1350-1357.
• Major S, Pettigrew RW, Fyfe JC (2015). Molecular genetic characterization of thyroid dyshormonogenesis in a French Bulldog. J Vet Intern Med 29(6):1534-1540.
• Gonzalez KS, Warwick H, Conradie M, Alisauskaite N (2024). Clinical and magnetic resonance imaging findings in a French bulldog puppy with genetically confirmed congenital hypothyroidism. J Vet Intern Med 38(3):1737-1743.
• Donner J, Freyer J, Davison S, Anderson H, Blades M, Honkanen L, Inman L, Brookhart-Knox CA, Louviere A, Forman OP, Chodroff Foran R (2023). Genetic prevalence and clinical relevance of canine Mendelian disease variants in over one million dogs. PLoS Genet 19(2):e1010651.
• Donner J, Anderson H, Davison S, Hughes AM, Bouirmane J, Lindqvist J, Lytle KM, Ganesan B, Ottka C, Ruotanen P, Kaukonen M, Forman OP, Fretwell N, Cole CA, Lohi H (2018). Frequency and distribution of 152 genetic disease variants in over 100,000 mixed breed and purebred dogs. PLoS Genet 14(4):e1007361.
• Bojanic K, Acke E, Jones BR (2011). Congenital hypothyroidism of dogs and cats: a review. N Z Vet J 59(3):115-122.
• Graham PA, Refsal KR, Nachreiner RF (2007). Etiopathologic findings of canine hypothyroidism. Vet Clin North Am Small Anim Pract 37(4):617-631.
• O’Neill DG, Khoo JSP, Brodbelt DC, Church DB, Pegram C, Geddes RF (2022). Frequency, breed predispositions and other demographic risk factors for diagnosis of hypothyroidism in dogs under primary veterinary care in the UK. Canine Med Genet 9(1):11.
• Ris-Stalpers C, Bikker H (2010). Genetics and phenomics of hypothyroidism and goiter due to TPO mutations. Mol Cell Endocrinol 322(1-2):38-43.
• Arrigoni M, Zwaveling-Soonawala N, LaFranchi SH, van Trotsenburg ASP, Mooij CF (2025). Newborn screening for congenital hypothyroidism: worldwide coverage 50 years after its start. Eur Thyroid J 14(1):e240327.
• Online Mendelian Inheritance in Animals (OMIA). OMIA:000536-9615: Hypothyroidism, congenital in Canis lupus familiaris (dog). Sydney School of Veterinary Science, University of Sydney. Accessed 2026-10-12.
• Fyfe JC. Congenital Hypothyroidism with Goiter (CHG) in SWDs. Spanish Water Dog Club of America (SWDCA) health page. Accessed 2026-10-12.
• American Toy Fox Terrier Club (ATFTC). TFT Health Information. Accessed 2026-10-12.

About the author

Elena Marsh

Editor & writer (not a veterinarian)

A writer with a molecular-biology background and a lifelong dog and cat owner. Not a veterinarian — she translates peer-reviewed genetics research and primary data into plain language, always as information rather than diagnosis.