Ataxia and cerebellar anomalies - narrow panel

Gene: KCNN2

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.

Created: 5 Feb 2023, 5:18 p.m. | Last Modified: 5 Feb 2023, 5:18 p.m.

Panel Version: 3.30

Green List (high evidence)

Comment on list classification: There is enough evidence to promote this gene to Green at the next GMS panel update - cerebellar ataxia, with an early onset from childhood to adolescence, was reported in 4/10 individuals with distinct KCNN2 variants. Pathogenicity of variants was supported by functional data.

Created: 10 Feb 2021, 2:02 p.m. | Last Modified: 10 Feb 2021, 2:02 p.m.

Panel Version: 2.42

- PMID: 33242881 (2020) - 10 patients with de novo KCNN2 variants and one individual with a heterozygous missense variant inherited from an affected parent, detected by WES. Patch-clamp functional studies showed that all but one variant (p.Glu30Gln) tested, which was reclassified VUS, led to to a loss-of-function of SK2 channels.

Excluding the case with the VUS, one patient displayed DD, 4 patients exhibited mild ID, 3 patients had moderate ID, and 2 had severe ID. Other clinical characteristics include a movement disorder (6/10) including tremor (5), cerebellar ataxia (4), and extrapyramidal symptoms (4); epilepsy (2/10); white matter abnormalities (3/6). Authors note that the 4 individuals without a movement disorder were under the age of 16 years at the time of the study and there is a possibility that this manifestation may arise later in life.
Sources: Literature

Created: 10 Feb 2021, 2 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Intellectual disability; seizures; movement disorder

Publications

• 33242881