Even though the dysregulation of the SHH pathway and enhanced expression of the PTCH1 receptor in DS [209, 223, 252, 253] has been attributed, at least partially, to the triplication of APP [252], both SHH and PTCH1 are targets for transcriptional repression by PRC2 members [68, 236], and dysregulation of the SHH pathway can be caused by increased transcription of key pathway genes due to the increased dosage of HMGN1 and alleviation of PRC2 repression. The gene discussed is HMGN1; the disease is Dravet syndrome.