Neuroaxonal Dystrophy, NAD (Giant Schnauzer Type)

 

Gene: MFN2

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, MFN2 gene; c.1617_1619 del. GGA, p.(E539 del), exon14

Medical system: Neurological, neuromuscular, skeletal

Breeds: Schnauzer - Giant

Age of onset of symptoms: At birth

Neuroaxonal Dystrophy caused by a mutation in the MFN2 gene is a fatal neonatal genetic neurological disorder.  It involves defective development of the motor neurons of the central nervous system with swelling of axons in the brain stem, spinal cord and peripheral nerves.  Additional clinical features include curvature of the spine (scoliosis) and contracted joints.  There are no voluntary movements of limbs, and puppies die at birth due to respiratory failure.

Note that Neuroaxonal Dystrophies (NADs) of differing severities and age of onset are seen in different breeds and are caused by mutations in different genes.  Here is a summary:

NAD, Giant Schnauzer type.  A severe disease that is lethal at birth.  MFN2 gene, OMIA [2153].

NAD, Papillon type: A progressive neurological disease with onset of symptoms by 3-4 months and death by 7-8 months.  PLA2G6 gene, OMIA [2105]

NAD, Rottweiler type.  A slowly progressive degenerative disease with a young adult onset usually resulting in ethical euthanasia.  VPS11 gene, OMIA [2152].

NAD, Spanish Water Dog type. A progressive degenerative disease with an onset of 6-11 months and ethical euthanasia by 2 years. TECPR2 gene, OMIA [1975]

 

References:

OMIA link: [2153-9615]

Stee K, Van Poucke M, Lowrie M, et al. (2023) Phenotypic and genetic aspects of hereditary ataxia in dogs. J Vet Intern Med. [pubmed/37341581]

Fyfe JC, Al-Tamimi RA, Liu J, et al. (2011) A novel mitofusin 2 mutation causes canine fetal-onset neuroaxonal dystrophy.  Neurogenetics 12:223-232. [pubmed/21643798]

Fyfe JC, Al-Tamimi RA, Castellani RJ, et al. (2010) Inherited neuroaxonal dystrophy in dogs causing lethal, fetal-onset motor system dysfunction and cerebellar hypoplasia. J Comp Neurol. 518(18):3771-84. [pubmed/20563033]