Atlanto-axial malformation and instability in dogs with pituitary dwarfism due to an LHX3 mutation

J Vet Intern Med. 2015 Jan;29(1):207-13. doi: 10.1111/jvim.12523. Epub 2015 Jan 14.


Background: Canine pituitary dwarfism or combined pituitary hormone deficiency (CPHD) in shepherd dogs is associated with an LHX3 mutation and can lead to a wide range of clinical manifestations. Some dogs with CPHD have neurological signs that are localized to the cervical spine. In human CPHD, caused by an LHX3 mutation, anatomical abnormalities in the atlanto-axial (C1-C2) joint have been described.

Objectives: To evaluate the presence of atlanto-axial malformations in dogs with pituitary dwarfism associated with an LHX3 mutation and to investigate the degree of similarity between the atlanto-axial anomalies found in canine and human CPHD patients with an LHX3 mutation.

Animals: Three client-owned Czechoslovakian wolfdogs and 1 client-owned German shepherd dog, previously diagnosed with pituitary dwarfism caused by an LHX3 mutation, with neurological signs indicating a cervical spinal disorder.

Methods: Radiography, computed tomography, and magnetic resonance imaging of the cranial neck and skull, necropsy, and histology.

Results: Diagnostic imaging identified abnormal positioning of the dens axis and incomplete ossification of the suture lines between the ossification centers of the atlas with concurrent atlanto-axial instability and dynamic compression of the spinal cord by the dens axis. The malformations and aberrant motion at C1-C2 were confirmed at necropsy and histology.

Conclusions and clinical importance: The atlanto-axial abnormalities of the dwarf dogs resemble those encountered in human CPHD patients with an LHX3 mutation. These findings suggest an association between the LHX3 mutation in dogs with CPHD and atlanto-axial malformations. Consequently, pituitary dwarfs should be monitored closely for neurological signs.

Keywords: Ataxia; Canine; Growth hormone; Hypermetria; Opisthotonus.

MeSH terms

  • Animals
  • Atlanto-Axial Joint / abnormalities*
  • Dog Diseases / congenital*
  • Dog Diseases / genetics
  • Dogs
  • Dwarfism, Pituitary / genetics
  • Dwarfism, Pituitary / veterinary*
  • Female
  • LIM-Homeodomain Proteins / genetics
  • LIM-Homeodomain Proteins / metabolism*
  • Male
  • Mutation
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*


  • LIM-Homeodomain Proteins
  • Lhx3 protein
  • Transcription Factors