Small conductance calcium-activated potassium channels (SK) are a subfamily of potassium channels activated by intracellular calcium comprising four members (SK1-4) encoded by different genes (KCNN1-4). KCNN2 encodes the SK2 channel. SK2 is highly expressed in neurons and plays important roles in the regulation of neuron membrane excitability by calcium, synaptic transmission and plasticity.
Clinical features
KCNN2-related channelopathy exhibit variable clinical manifestations including developmental delay, intellectual disability, autistic features, and frequent movement disorders. Movement disorders include cerebellar ataxia, tremors, dyskinesia, bradykinesia/parkinsonism, myoclonus-dystonia, and motor tics.
A few patients have normal or borderline cognitive abilities and only present with movement disorders while others have only developmental delay, intellectual disability and behavioral disturbances.
Prevalence
The exact prevalence is not yet known but it is a rare disorder, with less than 20 patients reported so far.
Inheritance
KCNN2-related disorders follow autosomal dominant inheritance. Mutations causing severe sporadic disorders usually occur de novo while mutations associated with milder phenotypes can be inherited from affected parents, or be transmitted over several generations.
KCNN2