Cerebellar Hypoplasia

Cerebellar hypoplasia is a disease that affects the development of the cerebellum in dogs and causes non-progressive cerebellar ataxia.

Symptoms

Symptoms of cerebellar hypoplasia usually appear around 6 weeks of age in puppies and include uncoordinated jerky movements, loss of balance and severe tremors, especially during voluntary movements. Seizures and nystagmus may also occur. Fortunately, dogs with this condition usually show no signs of pain or discomfort.

Disease Management

There is currently no cure for cerebellar hypoplasia. Treatment generally involves managing symptoms and providing a safe environment that minimizes the chances of injury due to lack of coordination and balance. In some cases, dogs with cerebellar hypoplasia can lead relatively normal lives with proper care and support.

Genetic basis

This disease follows an autosomal recessive mode of inheritance. Autosomal recessive inheritance means that the dog, regardless of sex, must receive two copies of the mutation or pathogenic variant to be at risk of developing the disease. Both parents of an affected dog must carry at least one copy of the mutation. Animals with only one copy of the mutation are not at increased risk of developing the disease, but may pass the mutation on to future generations. Breeding between dogs carrying genetic variants that can cause disease, even if they do not show symptoms, is not recommended.

Technical report

The cerebellum is the part of the brain that regulates the control and coordination of movement. In cerebellar hypoplasia, also known as Dandy-Walker malformation, the nerve cells of the cerebellum do not develop properly, affecting balance and coordination. In dogs, cerebellar hypoplasia may be related to parvovirus infection in utero and, in some cases, is hereditary and caused by alterations in the VLDLR gene. The VLDLR gene encodes for the very low density lipoprotein receptor and together with apolipoprotein E receptor 2 (APOER2) forms part of the reelin signaling pathway that directs the process of neuroblast migration to the cerebral cortex and into the cerebellum. If these receptors are altered, the neuroblasts (which will give rise to nerve cells) do not migrate normally and the nervous system fails to develop properly. Gerber et al. identified the VLDLR mutation responsible for the disease in Eurasier dogs. They observed that those dogs that have two copies of the c.1713del mutation produce an afunctional VLDLR protein.

Most affected breeds

Eurasier

Bibliography

Bernardino F, Rentmeister K, Schmidt MJ,et al. Inferior cerebellar hypoplasia resembling a Dandy-Walker-like malformation in purebred Eurasier dogs with familial non-progressive ataxia: a retrospective and prospective clinical cohort study. PLoS One. 2015 Feb 10;10(2):e0117670.

Gerber M, Fischer A, Jagannathan V,et al. A deletion in the VLDLR gene in Eurasier dogs with cerebellar hypoplasia resembling a Dandy-Walker-like malformation (DWLM). PLoS One. 2015 Feb 10;10(2):e0108917.