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Forebrain Commissural Malformation, Ventriculomegaly, and Interhemispheric Cysts

Forebrain Commissural Malformation, Ventriculomegaly, and Interhemispheric Cysts

Commissural malformation of the prosencephalon in cats, accompanied by ventriculomegaly and interhemispheric cysts, is a congenital brain malformation that causes ataxia and neurological problems. This disease is associated with a deletion in the GDF7 gene involved in the formation of the nervous system and bone and cartilage development.

Symptoms

Clinical signs of commissural malformation of the prosencephalon, ventriculomegaly and interhemispheric cysts include mild generalized ataxia on walking and postural reaction deficits ranging from mild to severe. In addition, cats with neurological symptoms have midline and limbic structure abnormalities. The severity of the brain malformation is variable, with most cats showing hydrocephalus (excessive accumulation of cerebrospinal fluid). The phenotype of affected cats is characterized by short, rounded ears and a domed head.

Disease Management

Disease management includes supportive care to improve quality of life, as well as physical therapy to help improve uncoordinated movement.

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

Commissural malformation of the forebrain, accompanied by ventriculomegaly (abnormally large ventricles) and interhemispheric cysts is a congenital disease and comparable to a mild form of holoprosencephaly in humans. The gene affected in this disease is GDF7, also known as bone morphogenetic protein 12 (BMP12), which belongs to the transforming growth factor beta (TGF-β) superfamily. GDF7 is crucial for the specification of neuronal identity in the spinal cord in addition to participating in bone and cartilage formation. The genetic variant described is a 7 base pair deletion in the coding region of GDF7 (c.221_227delGCCGCGC), resulting in a truncated protein. The deletion is responsible for the production of a dysfunctional protein, which is associated with the brain malformations observed in these cats.

Most affected breeds

Toyger

Bibliography

Keating MK, Sturges BK, Sisó S, et al. Characterization of an Inherited Neurologic Syndrome in Toyger Cats with Forebrain Commissural Malformations, Ventriculomegaly and Interhemispheric Cysts. J Vet Intern Med. 2016 Mar-Apr.