Congenital hypothyroidism with goitre due to dyshormonogenesis in the French Bulldog, caused by a splicing mutation of the TPO gene that abolishes thyroid peroxidase activity. It presents with cretinism, growth retardation, dysmorphic features and goitre. It is a case described in a single dog and its population frequency is unknown. A complementary test, not a substitute, for clinical examination.

Isolated case documented in the French Bulldog. Carrier frequency unknown. There is no evidence that it is a screening test in routine use in the breed; limited data.

- Growth retardation and small size for age
- Bilateral goitre (ventrolateral cervical masses)
- Lethargy, lack of response and poor suckling in puppies
- Delayed opening of the eyes and ear canals and delayed tooth eruption
- Abnormal hair and subcutis; macroglossia
- Low free and total T4 and elevated TSH
- Epiphyseal dysplasia and vertebral anomalies

In 2015 a case of congenital hypothyroidism with goitre was described in a 9-month-old female French Bulldog, with cretinism, bilateral goitre and undetectable TPO activity and protein. Sequencing identified a T>C transition at position +2 of the splice donor of intron 12 of TPO (c.2242+2T>C), which produces an mRNA with total or partial loss of exon 12. The mutant allele was not found in 125 clinically healthy French Bulldogs, which supports it being a rare variant.

- There is not yet a validated commercial test specific for c.2242+2T>C; the Rat Terrier/Toy Fox Terrier TPO test (c.331C>T) does not detect it
- In a puppy with goitre and elevated TSH, confirm the picture with the veterinarian and consider TPO sequencing
- If a carrier is confirmed, do not mate two carriers (25% affected)
- Do not present TPO-related CHG as common in the breed: the published data are from a single case

Canine congenital hypothyroidism due to TPO has been described in several breeds with different variants (French Bulldog, Spanish Water Dog, Rat Terrier, Toy Fox Terrier, Tenterfield Terrier). The French Bulldog case presented atypical features (survival without treatment for several months, thyroid fibrosis, almost normal epiphyseal maturation). Differential diagnosis with other causes of congenital hypothyroidism (dyshormonogenesis due to other genes, dysgenesis, acquired causes).

1. Major S, Pettigrew RW, Fyfe JC. 2015, Molecular genetic characterization of thyroid dyshormonogenesis in a French Bulldog. J Vet Intern Med 29(6):1534-40. PMID: 26478542. 2. Fyfe JC et al. 2013, A thyroid peroxidase (TPO) mutation in dogs reveals a canid-specific gene structure. Mamm Genome 24(3-4):127-33. PMID: 23223904. OMIA:000536-9615.