Genetic basis - Caused by mutations in the MYO5A gene, which encodes the motor protein myosin VA. The specific mutation causing this syndrome in dogs is a frameshift insertion in MYO5A, leading to a truncated nonfunctional protein. The mode of inheritance is autosomal recessive; dogs must have two copies of the mutation to be affected. Carrier dogs (one copy) show no symptoms but can pass the mutation to offspring
Pathophysiology - MYO5A protein is critical for the transport of melanosomes in pigment cells (melanocytes) and for neuronal function in the brain. Mutation leads to failure of melanosome transport resulting in coat color dilution (graying). Neurological symptoms occur due to disrupted intracellular transport in Purkinje cells of the cerebellum affecting motor control and coordination. Affected dogs exhibit neurological deficits shortly after birth such as inability to hold up their heads, lack of motor coordination, and poor response to stimuli.
Complication - Affected dogs have diluted fur color and severe neurological impairments. They cannot maintain upright posture, show poor reflexes, and often fall or collapse. The condition severely affects mobility and quality of life, requiring humane euthanasia in severe cases.
Why This Matters to Breeders and Vets - For breeders, identification of carriers prevents propagation of a devastating neurological and pigmentary disorder. Veterinarians rely on genetic and clinical data for early diagnosis, supportive care, and owner counseling. Knowledge of the autosomal recessive inheritance aids in breeding decisions and health management. Early diagnosis enables proper care and prevents unnecessary breeding of affected dogs.