Genetic basis of CCD in Hungarian Vizslas - is caused by a splice donor site mutation (c.2653+1G>A) in the SNX14 gene (Sorting Nexin 14). The SNX14 gene is involved in maintaining normal neuronal excitability and synaptic transmission. This mutation leads to degeneration and loss of Purkinje cells in the cerebellum, with secondary degeneration of granular and molecular cell layers, resulting in cerebellar atrophy. The disease is inherited in an autosomal recessive manner: affected dogs have two copies of the mutation (P/P), carriers one copy (N/P) and are asymptomatic, and clear dogs have no copies (N/N).
Pathophysiology - The mutation causes primary degeneration of Purkinje neurons in the cerebellar cortex. This leads to progressive loss of motor coordination due to dysfunction in cerebellar circuitry. Secondary effects include thinning of other cerebellar layers and overall cerebellar atrophy.
Clinical Signs and Progression - Progressive cerebellar ataxia (lack of coordination), Intention tremors and head tremors, Truncal sway and hypermetric/dysmetric gait, Insufficient menace response (loss of protective reflex), Positional horizontal nystagmus (involuntary eye movement), The progression is relatively fast after onset, severely impairing coordination and balance.
Summary - Cerebellar Cortical Degeneration in Hungarian Vizslas is a fatal autosomal recessive neurodegenerative disorder caused by a splice site mutation in the SNX14 gene. It presents with progressive cerebellar ataxia starting around 3 months of age due to Purkinje neuron loss and cerebellar atrophy. Genetic testing facilitates early diagnosis and supports breeding programs to reduce disease prevalence and prevent affected puppies.
