Genetic basis of Congenital Hypothyroidism - in cats is a rare autosomal recessive inherited endocrine disorder primarily caused by mutations in the thyroperoxidase (TPO) gene. The TPO gene encodes the enzyme thyroid peroxidase, which is essential for the synthesis of thyroid hormones by enabling iodine organification in the thyroid gland. Identified mutations include missense and other polymorphisms such as c.1333G>A (p.Ala445Thr) and c.430G>A (p.Gly144Arg), which impair TPO function. Affected cats inherit two copies of the mutation. Carriers with one copy do not usually show clinical signs but can pass the mutation to offspring. Molecular genetic testing is available to identify affected, carrier, and normal cats.
Pathophysiology - Thyroid peroxidase catalyzes iodination of tyrosine residues on thyroglobulin, a crucial step for producing thyroid hormones T3 and T4. Defective TPO enzyme function leads to: Reduced thyroid hormone synthesis (particularly T4), causing hypothyroidism. Feedback increase in thyroid-stimulating hormone (TSH), resulting in goiter (thyroid enlargement). Follicular hypoplasia and decreased colloid production in the thyroid gland tissue. Clinical hypothyroidism manifests as reduced metabolism and developmental abnormalities reflecting low thyroid hormone levels.
Complications - Affected cats present with: Disproportionate dwarfism with characteristic features such as large skull, short mandible, square trunk, short limbs, and occasionally kyphosis. Delayed eruption of deciduous and permanent teeth. Persistent juvenile hair coat and possible goiter. Mental deficiency and abnormalities of the central and peripheral nervous system. Other signs including hypothermia, lethargy, anorexia, constipation, and obesity. Secondary complications related to organ dysfunction caused by prolonged hormone deficiency.
Why This Matters to Breeders and Vets - Breeders: Genetic testing for TPO mutations enables identification of carriers and prevention of at-risk matings, reducing incidence of this serious developmental disorder. Domestic cats across multiple breeds have been shown to carry the mutations. Veterinarians: Awareness of clinical features suggestive of congenital hypothyroidism in young cats should prompt thyroid hormone testing and, where possible, genetic testing. Early diagnosis improves management outcomes. Recognition also helps differentiate CH from other growth or neurological disorders in kittens. Genetic counseling can support informed breeding decisions and reduce disease prevalence.
Summary - Feline Congenital Hypothyroidism is a rare autosomal recessive disorder caused by pathogenic mutations in the TPO gene, resulting in deficient thyroid hormone synthesis. This leads to developmental abnormalities including dwarfism, neurological deficits, goiter, and metabolic derangements in affected kittens. Diagnosis involves clinical signs, laboratory thyroid hormone assays, histopathology, and molecular confirmation of TPO mutations. Genetic testing is a valuable tool for breeders and veterinarians to identify carriers and affected cats and to guide breeding strategies for disease control.