Since a considerable proportion of CS, CS-like, BRRS and ASD-macrocephaly patients (from 20 to 90%, depending on the clinical entity) do not carry a PTEN germline pathogenic variant [2–5], it is relevant to continue searching for new genetic factors involved in PHTS development, to improve counseling, risk assessment and therapeutic measures for each patient. Here, PTEN is linked to Macrocephaly.