Ataxia and cerebellar anomalies - narrow panelGene: KCNN2
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.
Created: 10 Feb 2021, 2 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability; seizures; movement disorder
Gene: kcnn2 has been classified as Amber List (Moderate Evidence).
gene: KCNN2 was added gene: KCNN2 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature Q2_21_rating tags were added to gene: KCNN2. Mode of inheritance for gene: KCNN2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: KCNN2 were set to 33242881 Phenotypes for gene: KCNN2 were set to Intellectual disability; seizures; movement disorder Review for gene: KCNN2 was set to GREEN