Craniomandibular Osteopathy (SLC37A2 gene)

Craniomandibular osteopathy is a disease that affects the normal development of the bones of the jaw and face. The gene involved is SLC37A2, which encodes a key protein in glucose metabolism.

Symptoms

Symptoms usually appear between two and twelve months of age. Excessive salivation is the most commonly observed sign, although some animals also experience fever or other symptoms, such as depression or listlessness. Other warning signs include signs of distress when trying to eat, lack of appetite, intermittent fever, difficulty opening the mouth, protrusion of the eyes and swelling of the jaw.

Disease Management

Although there is no definitive cure for this disease, there are some treatments that can help relieve pain, such as the administration of anti-inflammatory drugs. In more severe cases, surgery may be used to correct the symptoms. It is important to note that the disease is self-limiting and tends to improve as the dog grows. However, the excess bone that forms in the jaw may not disappear completely and could persist beyond the dog's first year of life.

Genetic basis

This disease follows an autosomal dominant mode of inheritance with incomplete penetrance. Autosomal dominant inheritance means that dogs only have to inherit one copy of the mutation or pathogenic variant to be at risk of developing the disease. Incomplete penetrance occurs when not all dogs that carry the mutation eventually develop the disease or the symptoms vary in severity from one dog to the next. Each puppy born to a parent carrying one copy of the mutation has a 50% chance of inheriting one copy of the mutation and being at risk for the disease. Breeding between dogs carrying genetic variants that can cause disease is not recommended, even if they do not show symptoms.

Technical report

Craniomandibular osteopathy is a genetic disease caused by mutations in the SLC37A2 gene. This gene appears to play an essential role in the glucose homeostasis of key cells involved in osteogenesis. A synonymous variant has been described in exon 15 of the SLC37A2 gene consisting of the substitution of a C for a T (c.1332 C>T). Despite being a synonymous mutation, the mutant T allele eliminates a potential binding site for the ASF/SF-2 splicing factor. A study by Letko et al. (2020) identified in the Basset Hound breed another variant in heterozygosity in the SCL37A2 gene, which is likely to be pathogenic (c.1446+1G>A). However, this variant is not included in our test.

Most affected breeds

Cairn Terrier
Scottish Terrier
West Highland White Terrier

Bibliography

Hytönen MK, Arumilli M, Lappalainen AK,et al. Molecular Characterization of Three Canine Models of Human Rare Bone Diseases: Caffey, van den Ende-Gupta, and Raine Syndromes. PLoS Genet. 2016 May 17;12(5):e1006037.

Letko A, Leuthard F, Jagannathan V,et al. Whole Genome Sequencing Indicates Heterogeneity of Hyperostotic Disorders in Dogs. Genes (Basel). 2020 Feb 4;11(2):163.