Bi-allelic NRXN1 loss-of-function, also referred to as Pitt-Hopkins-like syndrome 2 (OMIM #614325), represents the most severe end of the clinical spectrum associated with NRXN1 disruption (Zweier et al., 2009; Castronovo et al., 2020; Fuccillo and Pak, 2021). This evidence concerns the gene NRXN1 and Pitt-Hopkins-like syndrome 2.