In 2017, a paper was published in Human Mutation describing a missense variant in ADGRB2 in a patient presenting with developmental delay and progressive spastic paraparesis; features shared with identical twins FAM_4_13 and FAM_4_10 harbouring a de novo pLoF in the same gene.(33) The authors showed that their specific variant demonstrated gain of function. Here, ADGRB2 is linked to Global developmental delay.