PRRT2 and autism spectrum disorder: In Subject #5 with severe NDD, we identified a c.649dup (p.R217fs*8) pathogenic variant in the PRRT2 gene in trans with the recurrent 16p11.2 BP4-BP5 deletion, providing compelling evidence for a novel disease AR trait inheritance mechanism for PRRT2. The 16p11.2 BP4-BP5 recurrent deletion is known to be associated with mild dysmorphisms, macrocephaly, and neuropsychiatric phenotypes including DD/ID and autism spectrum disorder (ASD) with incomplete penetrance, a NDD [73, 74].