Genetic basis - The condition in Toy Fox Terriers is caused by an autosomal recessive nonsense mutation in the thyroid peroxidase (TPO) gene. The specific mutation is a c.331C>T transition in the TPO gene. TPO is the enzyme responsible for iodide organification, a critical step in thyroid hormone biosynthesis. Mutation results in defective thyroid hormone production leading to hypothyroidism and goiter.
Pathophysiology - Affected puppies are hypothyroid from birth due to the lack of thyroid hormone production. The thyroid gland enlarges (goiter) due to persistent thyroid-stimulating hormone (TSH) stimulation. Symptoms appear within the first weeks of life when maternal thyroid hormone protection wanes. Hypothyroidism affects metabolism, growth, and neurological development.
Complications - Swelling in the neck due to goiter. Growth retardation, dwarfism. Lethargy, failure to suckle. Delayed tooth eruption, delayed opening of eyes and ear canals. Skeletal deformities such as limb and vertebral dysplasia. Poor coat quality. If untreated, the condition is lethal.
Inheritance - Autosomal recessive; affected dogs inherit two copies of the mutated gene. Carriers harbor one copy and are clinically normal but can pass the mutation to offspring. Clear dogs have no copies and do not carry or transmit the mutation.
Why This Matters to Breeders and Vets - Breeders: DNA testing identifies carriers and supports responsible breeding to avoid affected puppies. Vets: Early diagnosis and thyroid hormone replacement therapy significantly improve outcomes. Untreated puppies generally do not survive.