title: Atlanto-axial malformation and instability in dogs with pituitary dwarfism due to an LHX3 mutation.
abstract: 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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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
  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.
authors.affiliation: Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
authors.forename: A M W Y
authors.initials: AM
authors.lastname: Voorbij
authors.forename: B P
authors.initials: BP
authors.lastname: Meij
authors.forename: L W L
authors.initials: LW
authors.lastname: van Bruggen
authors.forename: G C M
authors.initials: GC
authors.lastname: Grinwis
authors.forename: Q E M
authors.initials: QE
authors.lastname: Stassen
authors.forename: H S
authors.initials: HS
authors.lastname: Kooistra
mesh_terms: D000818:Animals; D001268:Atlanto-Axial Joint / Q000002:abnormalities*; D004283:Dog Diseases / Q000151:congenital* / Q000235:genetics; D004285:Dogs; D004393:Dwarfism, Pituitary / Q000235:genetics / Q000662:veterinary*; D005260:Female; D060850:LIM-Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009154:Mutation; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D060850:LIM-Homeodomain Proteins; C094898:Lhx3 protein; D014157:Transcription Factors
keywords: Ataxia; Canine; Growth hormone; Hypermetria; Opisthotonus