Ehlers-Danlos Syndrome (Chihuahua)

Gene: COL5A2

Transmission: Autosomal dominant

For an autosomal dominant genetic disease, an animal must have at least one copy of the mutation in question to be at risk of developing the disease.  Animals with two copies of the mutation generally have more severe symptoms and an earlier onset of the disease than animals with just one copy of the mutation.  One or both of the parents of an animal with the mutation has one or two copies of the mutation.  Animals that have one or two copies of the mutation can pass the mutation on to future generations.

Mutation: Deletion, COL5A2 gene; c.3388_3414 del, p.(Lys1130_Asp1138 del)

Medical system: Dermal

Breeds : Chihuahua, Chinese Crested, Danish Swedish Farmdog, German Pinscher, German Shorthaired Pointer, Miniature Pinscher, Pomeranian, Poodle - Toy, Shih Tzu

Age of onset of symptoms: young age

Ehlers-Danlos Syndrome is a defect in a collagen gene (COL5A2) that can lead to skin hyperextensibility, skin tissue fragility, delayed healing, ocular degeneration and joint hypermobility. A history of lacerations is frequently noted in the anamnesis.  Diagnosis includes a skin extensibility index greater than 14.5% and histopathology of the dermis showing abnormal collagen.  Although there is no cure, a dog suffering from Ehlers-Danlos syndrome can enjoy a good quality of life thanks to a well-controlled environment that protects it from injury.  The mutation in the COL5A2 gene was first reported in the Chihuahua although in a recent survey of pathogenic mutations, Donner et al. (2023) reported the presence of the mutation in several additional breeds.

It should be noted that the same disease can be caused by a mutation in another collagen gene (COA5A1), this time seen in Labrador and mixed breed dogs [OMIA 2165-9615].

References:

OMIA link: [2295-9615]

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]

Kiener S, Chevallier L, Jagannathan V, et al. (2022) COL5A2 in-frame deletion in a Chihuahua with Ehlers-Danlos syndrome. Genes (Basel) 13:934. [pubmed/35627319]

Vroman R, Malfait AM, Miller RE, et al. (2021) Animal models of Ehlers-Danlos syndromes: Phenotype, pathogenesis, and translational potential. Front Genet 12:726474. [pubmed/34712265]

Malfait F, Castori M, Francomano CA, et al. (2020) The Ehlers-Danlos syndromes. Nat Rev Dis Primers 6:64. [pubmed/32732924]

Bauer A, Bateman JF, Lamandé SR, et al. (2019) Identification of two independent COL5A1 variants in dogs with Ehlers-Danlos syndrome.  Genes (Basel) 10(10):731. [pubmed/31546637]

Contributed by: Sandrine Beaumont-Courteau and Jay Muir, class of 2027, Veterinary Medicine Faculty, University of Montreal.  (Translation: DWS).