Indeed, in family 16DG1465 that lost four children with Hirschsprung disease, gastroesophageal reflux disease, coarse facial features, severe global developmental delay, agenesis of the corpus callosum, failure to thrive, and cataract, exome sequencing was negative but RNA-seq as described before [36] highlighted an abnormal profile of EPG5 and subsequent analysis revealed a homozygous deletion of exon 1 (Fig. 5). The gene discussed is EPG5; the disease is Hirschsprung disease.