Main clinical features:Mutations in VRK1cause neurological disease. The most common feature is disease of the motor neurons, which progressively affects muscle movement and strength. The age at which muscle weakness begins is highly variable, and onset of weakness ranges from infancy to adulthood. This motor neuron disease, particularly if occurring only in late childhood or adulthood, is usually not associated with cognitive impairment.
However, in some cases there is also brain involvement, which manifests as small head (microcephaly) at birth, often accompanied by various defects in brain structure. Patients with brain involvement usually have developmental delays of varying severity.
Inheritance:VRK1-associated disease is inherited in a manner called “autosomal recessive”. In our cells, there are two copies of every gene, including VRK1. One copy is inherited from the biological mother, and one copy from the biological father. VRK1-associated disease occurs when there is a mutation on both copies of the VRK1gene. This generally occurs when each biological parent is a carrier, i.e. each parent has one copy of VRK1 that is normal, and one copy that harbors a mutation. If both biological parents pass on the copy with the VRK1 mutation, their offspring will have a mutation on both copies of VRK1. Carrier couples have a 25% chance of having a child with VRK1-associated disease in every pregnancy. This can occur equally in female or male children.
Prevalence:VRK1-associated disease is very rare in most populations. Fewer than 30 patients have been described in the medical literature as of 2020. However, among Ashkenazi Jews there is a specific recurring mutation in VRK1. Approximately 1/230 healthy Ashkenazi Jews is a carrier of this mutation, which is associated with a severe form of VRK1disease including congenital brain involvement. Even among Ashkenazi Jewish couples, the prevalence of VRK1-associated disease would be expected to be ~ 1/200,000 births.
VRK1