LGI1 and Encephalopathy: This hypothesis is supported by the presence of 9 truncating variants of the canonical ADAM22 transcript in the ExAC database, whereas there are none for LGI1. Lack of rare biallelic mutations in ADAM22 in other exome data sets (appendix e-1) indicates that ADAM22-associated encephalopathy is rare, which may partially be because complete knockout mutations of ADAM22 are not tolerated and only hypomorphic mutations cause a phenotype similar to that in our study.