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Craniomandibular Osteopathy (CMO)
| Acronym: | CMO |
| Gene: | SLC37A2 |
| Mutation: | c.1332C>T |
| Inheritance: | Autosomal dominant with incomplete penetrance |
| Sample type: | Cheek Swab, Whole Blood (EDTA) |
Genetics and characteristics
Craniomandibular osteopathy (CMO) is a non-neoplastic (non-tumorous) disease affecting young dogs. It is most common in Scottish terriers, West Highland white terriers, and cairn terriers, but has been diagnosed also in other dog breeds. As the ability to eat and drink is crucial for living, disorders of the eating or drinking system can be extremely severe. The process of eating and drinking are coordinated by activities of the brain and its hunger and thirst center, as well as physical functions of the nose, mouth, esophagus, and gastrointestinal tract. Holding and chewing of the food is allowed by the dog’s bones of the skull, muscles of chewing, attached ligaments, and tendons. Two primary bones of the dog’s mouth are the mandible (the lower jawbone) and the maxilla (the upper jawbone). These two bones meet at the temporomandibular joint (TMJ), which is crucial for the opening and closing of the jaw, coordinated by the muscles of the cheek. Craniomandibular osteopathy (CMO) causes excessive bone formation along the mandible (the lower jaw) and the temporomandibular joint, resulting in difficulties and pain when opening the mouth during eating or drinking.
Symptoms of the disorder appear between 4 to 8 months of puppy’s age, can vary from mild to severe and they appear equally in both genders, male and female. Craniomandibular osteopathy symptoms include progressively worsening pain upon opening the mouth, loss of appetite, difficulty opening the mouth, difficulty picking up food with the mouth and chewing, excessive drooling, bulging eyes due to swelling inside the skull, and jaw swelling. The jaw is thickened from both sides (bilaterally), causing several bones to become so large and tender that full opening of the mouth becomes impossible. The tenderness of the jaw is accompanied by a fever of 3 to 4 days of duration. Fever is reoccurring with every new bone proliferation phase, which is happening every 2 to 4 weeks. Lymphadenopathy or temporal muscle atrophy may be present, as well as hypertrophic bones in the soft tissues adjacent to long bones. CMO can be diagnosed with radiography, which will show abnormal bone growth. Blood tests show normal erythrocytes, leukocytes, hemoglobin, calcium, phosphorus, and alkaline phosphatase levels.
Craniomandibular osteopathy (CMO) is caused by a mutation in the SLC37A2 gene and has been recognized as a disorder with autosomal dominance with incomplete penetrance mode of inheritance. SCLA37A2 is a transporter protein in osteoclasts, and it plays a central role in glucose homeostasis within these cells that participate in osteogenesis. Mutations within this gene cause improper glucose supply in the osteoclasts, resulting in abnormal development of the bone and hyperostosis. Considering the mutated gene, dogs can be clear homozygous, carrier heterozygous, and affected homozygous. Heterozygous carrier has one copy of the mutated gene, is at low risk of developing symptoms of CMO, and has a 50% chance of passing the mutation on to their offspring. The affected homozygous dog has two copies of the mutated gene and is at high risk of developing disorder symptoms. Studies have shown that 84% of the dogs showing symptoms of CMO were homozygous affected. However, it is possible that some of the homozygous affected dogs look normal, and without showing any symptoms, they will 100% transmit the mutation to all their offspring. Research has shown that within the population of 303 West Highland white terriers, the frequency of the mutated gene was high, about 36%.
Results Reported As
Test Result |
Interpretation of test result |
CLEAR |
Tested mutation was not detected in animal with „clear“ result. Animal tested as clear has wild-type allele in homozygous state (i.e. two pairs of healthy alleles). It will not develop disease caused by tested mutation.* It will pass only wild-type allele to its offspring. |
AFFECTED HETEROZYGOTE |
Tested mutation was detected in animal with „affected heterozygote“ result. Animal tested as affected heterozygote has one wild-type and one mutation allele, it is in heterozygous state. It is likely to develop disease caused by tested mutation.* It can pass wild-type or mutation allele to its offspring. |
AFFECTED |
Tested mutation was detected in animal with „affected“ result. Animal tested as affected has two copies of mutation alleles affecting the gene. It is likely the animal will experience a genetic disorder due to this mutation.** It will pass only mutation allele to its offspring. |
*Test excludes only tested mutation but not possible unknown mutations or factors that can lead to similar condition/symptoms.
**Penetrance of tested mutation, and potential unknown mutations or multiple other factors can possibly affect the likelihood of experiencing a genetic disorder.
References:
Marjo K. Hytönen,Affiliations Meharji Arumilli, Anu K. Lappalainen, AffiliationMarta Owczarek-Lipska, Vidhya Jagannathan, AffiliationSruthi Hundi, AffiliationsElina Salmela, AffiliationsPatrick Venta, Eva Sarkiala, Tarja Jokinen, Daniela Gorgas, Juha Kere, Pekka Nieminen, Cord Drögemüller , Hannes Lohi et al. (2016.): Molecular Characterization of Three Canine Models of Human Rare Bone Diseases: Caffey, van den Ende-Gupta, and Raine Syndromes. PLoS Genet 12(5): e1006037. doi:10.1371/journal.pgen.1006037