Congenital Hypothyroidism with Goiter

 

Gene: TPO

Transmission: Autosomal recessive

For an autosomal recessive genetic disease an animal must have two copies of the mutation in question to be at risk of developing the disease.  Both parents of an affected animal must be carriers of at least one copy of the mutation.  Animals that have only one copy of the mutation are not at risk of developing the disease but are carrier animals that can pass the mutation on to future generations.

Mutations:

French Bulldog mutation: Splicing error, TPO gene; c.2242+2 T>C

Rat Terrier mutation: Substitution TPO gene; c.331 C>T, p.(Q111Stop)

Spanish Water Dog mutation: Insertion, TPO gene; c.39_40 ins.G

Tenterfield Terrier mutation: Substitution, TPO gene; c.1777 C>T, p.(R594W)

Medical system: Endocrine

Breeds: American Hairless Terrier, American Staffordshire Terrier/Amstaff, Beagle, Carlin Pinscher, Chihuahua, Dachshund Miniature Longhair/Shorthair, Decker Terrier, Fox Terrier, Fox Terrier - Miniature, French Bulldog, Rat Terrier, Spanish Water Dog, Teddy Roosevelt Terrier, Tenterfield Terrier, Yorkshire Terrier

Age of onset of symptoms: Around the age of 3 to 8 weeks

Congenital Hypothyroidism with goiter of the Tenterfield Terrier is a genetic metabolic disease of the newborn. Affected animals lack an enzyme necessary for the production of thyroid hormones.  These individuals are smaller than normal and are lethargic.  Additional signs include goiter (swelling in the neck), dwarfism with a disproportionately large head, delayed epiphyseal ossification, and delayed development of guard hairs.  The condition, if diagnosed early, can be treated by medication.  If goiter is present, it can develop to the point of interfering with normal breathing.  It can continue to develop and can sometimes prevent the animal from breathing normally.

 

References:

OMIA link: [0536-9615]

Bugbee A, Rucinsky R, Cazabon S, et al. (2023) 2023 AAHA selected endocrinopathies of dogs and cats guidelines. J Am Anim Hosp Assoc 59:113-135.  [pubmed/37167252]

Donner J, Freyer J, Davison S, et al. (2023) Genetic prevalence and clinical relevance of canine Mendelian disease variants in over one million dogs.  PLoS Genet. 19(2):e1010651. [pubmed/36848397]

Ringstad NK, Lingaas F, Thoresen SI. (2022) Breed distributions for diabetes mellitus and hypothyroidism in Norwegian dogs. Canine Med Genet 9:9. [pubmed/35610669]

Soler Arias EA, Castillo VA, Garcia JD, Fyfe JC (2018) Congenital dyshormonogenic hypothyroidism with goiter caused by a sodium/iodide symporter (SLC5A5) mutation in a family of Shih-Tzu dogs. Domest Anim Endocrinol 65:1-8. [pubmed/29777899]

Åhlgren J, Uimari P. (2016) Heritability of hypothyroidism in the Finnish Hovawart population. Acta Vet Scand 58:39. [pubmed/27267591]

Bianchi M, Dahlgren S, Massey J, et al. (2015) A Multi-Breed Genome-Wide Association Analysis for Canine Hypothyroidism Identifies a Shared Major Risk Locus on CFA12. PLoS One. 10(8):e0134720. [pubmed/26261983]

Fyfe JC, Lynch M, Olsen J, Louёr E. (2013) A thyroid peroxidase (TPO) mutation in dogs reveals a canid-specific gene structure. Mamm Genome 24(3-4):127-133. [pubmed/23223904]

Dodgson SE, Day R, Fyfe JC. (2012) Congenital hypothyroidism with goiter in Tenterfield terriers. J Vet Intern Med 26:1350-1357. [pubmed/23113744]