Proper function of these proteins is critical for the development of the CNS, particularly the cerebellum.36 Although no effect of rs16859966 on ZIC1 or ZIC4 expression is recorded in the Genotype Tissue Expression database, rare genetic variants or deletions in ZIC1 or ZIC4 result in congenital cerebellar defects.35,36,43 A heterozygous deletion of ZIC1 and ZIC4 causes the Dandy–Walker malformation, a developmental disorder of the cerebellum.35,44 Remarkably, two recent epigenomic analyses in brain tissue of MSA point to ZIC4. This evidence concerns the gene ZIC4 and multiple system atrophy.