Cerebral Dysgenesis

Feline cerebral dysgenesis is a neurological disease characterized by a smooth and lissencephalic brain due to an alteration in the expansion and folding of the cerebral cortex. This disease has been associated with an alteration in the PEA15 gene, which is involved in intracellular signaling.

Symptoms

Symptoms of feline cerebral dysgenesis usually appear between the third and fourth week of the cat`s life, manifesting mainly as spastic tetraparesis (partial weakness and muscle stiffness in all four limbs) and ataxia. These symptoms tend to stabilize between 6 and 9 months of age. At around 18 months of age, affected cats may develop sensory abnormalities, such as staring into empty space or exhibiting attacking or biting behaviors without visible stimuli. In addition, there may be an increased level of aggression and, in some rare cases, seizures.

Disease Management

No preventive or curative treatment is available for this disease. Care focuses on the use of medications, when necessary, to control symptoms such as seizures, tremors or behavioral disturbances.

Genetic basis

This disease follows an autosomal recessive mode of inheritance. Autosomal recessive inheritance means that the cat, 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 cat 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 cats carrying genetic variants that may cause disease, even if they do not show symptoms, is not recommended.

Technical report

Gyrification is a key process in mammalian brain development, where the cerebral cortex expands and folds, being fundamental for its correct functioning. In the case of feline cerebral dysgenesis, a genetic variant related to the alteration of the PEA15 protein, crucial in cell signaling, has been discovered. The pathogenic variant described in this gene consists of a single nucleotide deletion in PEA15 (c.176del), which causes profound abnormalities in brain development in cats, such as microcephaly and polymicrogyria. Although affected cats have no obvious abnormalities in appearance or behavior, PEA15 deficiency is associated with severe neuropathological abnormalities.

Most affected breeds

Not specified

Bibliography

Graff EC, Cochran JN, Kaelin CB, et al. PEA15 loss of function and defective cerebral development in the domestic cat. PLoS Genet. 2020 Dec 8