The literature indicates that high ID diagnostic yields are attained by applying the following sequential testing strategy using validated methods, after a detailed clinical evaluation: numeric and structural chromosomal abnormalities analysis, FXS testing, MECP2 (females) and PTEN genes investigation (in the presence of ASDs with macrocephaly) [183], CNVs screening by CMA [184] and exome sequencing [87, 185]. The gene discussed is MECP2; the disease is Macrocephaly.