Atlantoaxio-Occipital Malformation

 

Gene: HOXD3

Transmission: Autosomal recessive

For an autosomal recessive genetic disease an animal must have two copies of the mutation in question to be at risk of developing the disease. Both parents of an affected animal must be carriers of at least one copy of the mutation. Animals that have only one copy of the mutation are not at risk of developing the disease but are carrier animals that can pass the mutation on to future generations.

Mutation: Deletion of 2,7kb between genes HOXD4 and HOXD3, chr.18.

Medical system: Skeletal

Breeds: Arabe

Age of onset of symptoms: Between birth and 8 months.

A phenotype of occipitoatlantoaxial malformation (OAAM) is observed in Arabian foals.  This is a structural anomaly whereby the 1st cervical vertebra (atlas bone) resembles the base of the skull (occiput bone) and the 2nd cervical vertebra (axis bone) resembles the atlas.  Malformations mainly lead to joint defects, spinal canal stenosis and associated proprioceptive and motor neurological problems.  Affected animals have an abnormal posture, a loss of flexibility of the neck, and can suffer from progressive ataxia.   Diagnosis is based on clinical signs and confirmed by X-ray.Molecular studies revealed a 2.7 kb deletion between the HOXD3 and the HOXD4 genes located on chromosome 18.  The HOX genes are important for organizing the axial and appendicular skeleton during early embryo development; HOX3 in particular is important for the organization of the occiput, atlas and axis bones.  A survey of 162 Arabian horses revealed a carrier frequency of 1.2% for the mutation, and a DNA test will now allow breeders to eliminate this mutation from their animals through selective breeding.  It should be noted however that not all Arab foals with a diagnosis of OAAM are positive for the 2.7 kb deletion genotype.  Furthermore, variations in details of the OAAM phenotype suggest that the condition involves genetic heterogeneity.

 

References:

OMIA link: [0081-9796]

Bordbari MH, Penedo MC, Aleman M, et al. (2017) Deletion of 2.7 kb near HOXD3 in an Arabian horse with occipitoatlantoaxial malformation. Anim Genet 48(3):287-294.  [pm/28111759]

Mayhew IG, Watson AG, Heissan JA. (1978) Congenital occipitoatlantoaxial malformations in the horse. Equine Vet J 10:103-13.  [pm/565704]

 

Contribution par : Justine Gagnon and Sarah-Maude Grondin, promotion 2028, Faculté de médecine vétérinaire, Université de Montréal.