Genetic screening of PTEN in the whole sample of ASD-macrocephaly, either with or without epilepsy\EEG abnormalities, revealed the presence of a novel heterozygous frameshift mutation (c.43delA; p.R15Dfs*9) (Figure 1A) in one case with “extreme” macrocephaly, autism, intellectual disability and history of a first unprovoked seizure. This evidence concerns the gene PTEN and Macrocephaly.