Main Clinical Features
The KCNMA1-linked channelopathy is a heterogenous multisystem disorder characterized by overlapping combinations of seizure/epilepsy disorder, movement disorder phenotypes, developmental delay, intellectual disability and in some cases brain and structural malformations.
Prevalence
KCNMA1-linked channelopathy is a rare condition. Due to the small number of identified cases there is difficulty determining unbiased prevalence of the condition. Currently there are 103 documented patients and further studies are needed to determine the precise prevalence. The allele frequencies are estimated to be 1:100,000 for KCNMA1 variants, like other rare diseases estimated by Lek et al. (2016).
Inheritance
KCNMA1-linked channelopathy is associated with several single nucleotide variant (SNV) alleles including gain of function variants, loss of function variants and variants of unknown significance. Miller et al. summarized data from the Sanford Research Rare Disease Registry and published literature including 37 KCNMA1 alleles from 69 patients. Of these variants, the vast majority of alleles presented as apparent autosomal dominant heterozygous de novo occurrences. Only two alleles were confirmed autosomal recessive homozygotes, and one allele was a de novo homozygous occurrence.
KCNMA1