Product Description

Dandy-Walker-Like Malformation (DWLM)

Dandy-Walker-Like malformation (DWLM) is a genetic disorder affecting the Eurasier dog breed. It is a result of abnormal brain development caused by a genetic mutation. The Eurasier dog breed originated in Germany in 1960 and was created by crossing the Samoyed, Chow Chow and the Wolfspitz dog breed. Since the Eurasier are a young dog breed and have started with only small number of dogs, inbreeding rate was high which significantly increased the risk of obtaining puppies affected by recessive inherited disorders.

Name of the disorder, Dandy-Walker-Like malformation (DWLM), comes from inherited brain malformation in humans, the Dandy-Walker syndrome (DWS). DWS was named after American neuroscientists, Walter Dandy and Arthur Earl Walker.

Symptoms

The brain malformation involves the cerebellum and the fluid-filled spaces around it. Cerebellum, or also known as the little brain, plays an important role in motor control through regulation of coordination, precision and motor learning. Any disease that affects the cerebellum has an effect on the coordination and can cause ataxia. Main characteristic of the disorder is cerebellar hypoplasia, enlargment of the fourth ventricle and very small or completely absent part of the brain that is located between two hemispheres, known as cerebellar vermis. Fourth ventricle is part of ventricular system and it is one of the cavities filled with fluid within the brain and it is a site of common occurrence of a form of brain tumor-intracranial ependymomal tumour. Other examinations can also show the posterior midline area of cerebellar cortex responsible for coordination of the muscles and cyst formation near the internal base of the skull. Visible symptoms may be vomiting, mental retardation, intracranial pressure seen as macrocephaly, prominent forehead and irritability. All these abnormalities commonly result in problems with movement, coordination, intellect, mood, and other neurological functions. DWLM affected dogs display a non-progressive form of cerebellar ataxia. The ataxia varies among dogs in its severity, from mild truncal sway, mild lack of movement coordination, subtle dysmetric gait, imbalance and pelvic limb ataxia to severe cerebellar ataxia in puppies and episodic falling or rolling. Some affected dogs exhibits epileptic seizures.

Genetics

Dandy-Walker-Linke malformation (DWLM) is caused by a mutation in the VLDLR gene. VLDLR gene is encoding for a transmembrane receptor VLDLR that belongs to the low density lipoprotein receptor family (LDL). Together with another receptor, it has a role in biochemical pathway that controls neuroblast migration in the cerebral cortex and cerebellum. Neuroblast is a cell that will develop into a neuron after this migration phase. When VLDLR receptor is absent or unfunctional, neuroblast migration cannot occur, which results in an undeveloped central nervous system.

The disorder is inherited in an autosomal recessive manner. Regarding the mutated gene, dog can be clear, carrier or affected. Healthy parents of an affected puppy are obligate heterozygotes, and therefore carry one mutant allele. Heterozygotes have no symptoms. Dogs homozygous for the mutation will display the symptoms of the Dandy-Walker-Linke malformation (DWLM). At conception, each cub has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. In a research conducted in Switzerland, 16% of tested dogs were heterozygous carries. This high carrier rate proves importance of DWLM genetic testing, in order to avoid obtaining affected puppies.

References:

Gerber M,Fischer A,Jagannathan V, Drögemüller M,Drögemüller C,Schmidt MJ et al. (2015): A Deletion in the VLDLR Gene in Eurasier Dogs with Cerebellar Hypoplasia Resemblinga Dandy-Walker-Like Malformation (DWLM). PLoS ONE10(2): e0108917.doi:10.1371/journal. pone.0108917.