Atlanto‐Axial Malformation and Instability in Dogs with Pituitary Dwarfism due to an LHX 3 Mutation

Background Canine pituitary dwarfism or combined pituitary hormone deficiency ( CPHD ) in shepherd dogs is associated with an LHX 3 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 LHX 3 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 LHX 3 mutation and to investigate the degree of similarity between the atlanto‐axial anomalies found in canine and human CPHD patients with an LHX 3 mutation. Animals Three client‐owned Czechoslovakian wolfdogs and 1 client‐owned German shepherd dog, previously diagnosed with pituitary dwarfism caused by an LHX 3 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 LHX 3 mutation. These findings suggest an association between the LHX 3 mutation in dogs with CPHD and atlanto‐axial malformations. Consequently, pituitary dwarfs should be monitored closely for neurological signs.