Clinical Characteristics

Most patients with KCNN2 pathogenic variants show delays in acquiring motor milestones and a speech delay or a regression of language abilities. 90% of patients also have intellectual disability although the degree of cognitive impairment is variable, ranging from mild to severe. Autism spectrum disorder (ASD) or autistic features can be observed, with an incomplete penetrance. Movement disorders are present in at least 60% of patients and present as cerebellar ataxia, dyskinesia, bradykinesia/parkinsonism, myoclonus-dystonia or choreic movements. Less frequent neurological features may motor tics (head jerking, eye blinking), nystagmus, peripheral neuropathy, or pyramidal signs. Movement disorders usually start in childhood or adolescence but may appear at mater stages and/or progress over time. 20% of patients exhibit seizures. MRI may reveal white matter abnormalities. Older subjects may present psychotic episodes or psychiatric features.

Clinical variability
The clinical presentation and severity of KCNN2-related disorders is highly variable from one family to the other but individuals with the same mutations tend to show more similar phenotypes.