We propose that (1) causal genes should be trisomic in mouse models with cerebellar hypoplasia; (2) variation in causal genes may be linked to SHH phenotypes outside of the context of Down syndrome; (3) in the absence of genetic interactions, causal genes should inhibit SHH signaling when overexpressed; and (4) causal genes should be expressed in the relevant cell types and misexpressed in trisomic cells. This evidence concerns the gene SHH and Down syndrome.