Cleft Palate with Syndactyly (CPS)

 

Gene: ADAMTS20

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.

Mutation: Deletion, ADAMTS20 gene; c.1360_1361 del.2bp, exon9

Medical system: Skeletal

Breed: Nova Scotia Duck Tolling

Age of onset of symptoms: At birth

Cleft palate with syndactyly (CPS) is a congenital anomaly seen in the Nova Scotia Duck Tolling Retriever (NSDTR) that involves a failure of the palate to close (cleft palate) in addition to fusion of the digits (syndactyly).  Puppies are born with a hole in the palate which makes suckling difficult, resulting in failure to thrive and increasing the chance of aspiration pneumonia.  A mutation in the ADAMTS20 gene is the genetic cause of CPS in the NSDTR.  However, the overall genetics of cleft palate in the NSDTR is complicated.  CP1 is a cleft palate phenotype caused by a mutation in a separate gene, and it is suspected that additional genetic factors (not as yet characterized) can also contribute to the phenotype.

 

References:

OMIA link: [1140-9615], [1919-9615]

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]

Goldschmidt S, Hoyer N. (2022) Management of dental and oral developmental conditions in dogs and cats. Vet Clin North Am Small Anim Pract 52:139-158.  [pubmed/34838248]

Freiberger K, Hemker S, McAnally R, et al. (2021) Secondary Palate Development in the Dog (Canis lupus familiaris). Cleft Palate Craniofac J. 58(2):230-236. [pubmed/32705901]

Roman N, Carney PC, Fiani N, Peralta S. (2019) Incidence patterns of orofacial clefts in purebred dogs. PLoS One. 14(11):e0224574.  [pubmed/31682628]

Peralta S, Fiani N, Kan-Rohrer KH, Verstraete FJM. (2017) Morphological evaluation of clefts of the lip, palate, or both in dogs. Am J Vet Res 78:926-933. [pubmed/28738009]

Wolf ZT, Brand HA, Shaffer JR, Leslie EJ. (2015) Genome-wide association studies in dogs and humans identify ADAMTS20 as a risk variant for cleft lip and palate. PLoS Genet 11:e1005059. [pubmed/25798845]

Wolf ZT, Leslie EJ, Arzi B, et al. (2014) A LINE-1 insertion in DLX6 is responsible for cleft palate and mandibular abnormalities in a canine model of Pierre Robin sequence. PLOS Genetics 10(4):e1004257. [pubmed/24699068]