Craniomandibular osteopathy (SLC35D1-related)

Gene: SLC35D1

Transmission: Autosomal dominant (complex genetics)

Mutation: Deletion, SLC35D1 gene: c.1021_1024 del.TCAG, p.(Ser341Arg frame shift STOP 22), Chr.5.

Medical system: Skeletal

Breed: Weimaraner

Age of onset of symptoms: Young dogs in growth phase (3 to 7 months)

Craniomandibular osteopathy (CMO) is a non-neoplastic proliferative bone disease that primarily affects the skull and mandible in young growing dogs and has been reported in many breeds. It involves complex genetics, with possibly multiple genes involved and mutations that may be breed specific.  In many cases, the disease remains transient and may even go undetected, which complicates studies of the genes and mutations involved.  CMO manifests as excessive new bone formation, leading to mandibular swelling, significant pain upon opening the mouth, difficulty eating (dysphagia), hypersalivation, and often fever during the active phase. In some cases, pain in the long bones (radius, ulna) may also be observed. The disease is generally self-limiting, meaning that clinical signs resolve once bone growth stabilizes and normal ossification is completed. Diagnosis is based on clinical examination and imaging that reveal irregular bone proliferation in the mandible or skull.

CMO was diagnosed in a Weimaraner dog where computed tomography (CT) scans revealed new, atypical bone formation in the mandible. Whole genome sequencing identified a heterozygous mutation in the SLC35D1 gene. The SLC35D1 gene codes for a nucleotide-sugar transporter involved in the biosynthesis of chondroitin sulfate, an essential component of cartilage formation and thus important for normal endochondral bone formation.  Further studies are now needed to determine if this mutation is indeed causative for CMO.

See also: Craniomandibular osteopathy (SLC37A2 linked), as seen in the West Highland White Terrier and related terrier breeds.

References:

OMIA link: [0236-9615]

Letko A, Leuthard, F, Jagannathan V, et al. (2020) Whole genome sequencing indicates heterogeneity of hyperostotic disorders in dogs. Genes (Basel) 11:163.  [pm/32033218]

With contributions by: Maxime Portmann and Laurent Savard, Class of 2030, Faculty of Veterinary Medicine, University of Montreal.  (Translation: DWS).