Congenital hypothyroidism is a hereditary disease in which the thyroid gland does not produce sufficient thyroid hormones from birth, usually due to a defect in hormone synthesis (iodine organification) that presents with goitre. It affects metabolism and development: kittens grow poorly, are apathetic and constipated and have altered skin and coat. Without levothyroxine treatment, growth retardation and cognitive impairment become irreversible, but with early diagnosis the prognosis is reasonable.

Van Poucke et al. (2022) found the c.514G>A variant in 15 breeds, with an estimated allele frequency of 9 % in the undiagnosed cats analysed; all affected cats were homozygous. The breeds include British shorthair, Russian Blue and domestic shorthair, semi-longhair and longhair populations. Breed-specific frequencies are scarce: limited data.

- Growth retardation and disproportionate dwarfism with short bones\n- Lethargy, drowsiness and little willingness to play\n- Persistent constipation\n- Thick skin, alopecia and dry, brittle coat\n- Goitre (enlargement of the thyroid gland) perceptible in the neck\n- Delayed tooth eruption, large skull with short jaw and ears\n- Central and peripheral nervous system alterations

Congenital hypothyroidism with goitre was documented in colonies and families of domestic cats, and its autosomal recessive pattern was established by studying affected litters (Mazrier et al., 2003). Biochemical characterisation pointed to a defect in thyroid peroxidase (TPO). Morrow et al. (2006) proposed a deletion in intron 9 of TPO, and Giger et al. (2015) described the variant c.1333G>A p.(Ala445Thr) (current nomenclature c.1418G>A p.(Ala473Thr)) in domestic shorthair cats. Van Poucke et al. (2022) identified the main current causal variant, c.430G>A p.(Gly144Arg) (current nomenclature c.514G>A p.(Gly172Arg)), in 11 affected cats from 10 families and 15 breeds. Gallego-Munevar et al. (2024) published a clinical case with a new mutation in TPO and heterozygous variants of uncertain significance, with suspected monoallelic expression.

- Test breeding animals of the included breeds: identifies clear and carrier animals.\n- Do not mate two carriers together.\n- A carrier may be mated to a clear animal; test the offspring intended for breeding.\n- In kittens with retarded growth and lethargy, request a full thyroid profile (total and free T4, TSH) before ruling out other causes.

Differential diagnosis with pituitary dwarfism, malnutrition, other congenital bone diseases and feline hepatic lipidosis. Laboratory findings show low T4 with elevated TSH and frequently high cholesterol; thyroid scintigraphy is compatible with a defect in iodine organification. Levothyroxine treatment is effective if started early: the growth and activity response within a few weeks confirms the diagnosis. Monitor for overdosing (tachycardia, weight loss, restlessness) with periodic hormone checks. The main variant c.514G>A and the historical variant c.1418G>A must be distinguished, as they are not equivalent.

1. Van Poucke M, Van Renterghem E, Peterson ME, et al. Association of recessive c.430G>A (p.(Gly144Arg)) thyroid peroxidase variant with primary congenital hypothyroidism in cats. J Vet Intern Med. 2022;36(5):1597-1606. PMID: 36054182.
2. Lyons LA. DNA mutations of the cat: the good, the bad and the ugly. J Feline Med Surg. 2015;17(3):203-219. PMID: 25701860.
3. Gallego-Munevar C, Carrillo-Godoy N, Rondón-Barragán IS. Molecular detection of a novel mutation in the TPO gene associated with congenital hypothyroidism in a cat: Case report. J Adv Vet Anim Res. 2024;11(4):1030-1036. PMID: 40013294.
4. OMIA:000536-9685. Hypothyroidism, congenital in Felis catus. https://omia.org/OMIA000536/9685/