Consistent with the previously reported findings, the present pediatric case heterozygous for a de novo missense change (p.Glu1289Lys) in POLR2A was affected by a severe and progressive form of neurodevelopmental syndrome with hypotonia, cognitive deficits, attention and behavioral disorders, associated with orofacial cleft, urological, skeletal, and facial anomalies. The gene discussed is POLR2A; the disease is Atypical behavior.