Overgrowth syndromes are characterized by a global or regional bulk increase in tissue volume. In fetal brain, these are generally characterized by a disorganized neural architecture in the affected areas; particularly in Tuberous sclerosis abnormal cytology is obvious in fetal life. Generally, overgrowth is initiated by constitutional or somatic mutations in elements of the PIK3–AKT–mTOR pathway. These include AKT1, AKT3, DEPDC5, FGFR2 and FGFR3, MTOR, NPRL2, NPRL3, PIK3CA, PIK3R2, PTEN, TSC1, and TSC2. Poorly regulated activation of a major promitotic pathway in either the germline or as somatic mutations in pluripotent central nervous system cells seems to lead to an excess generation of differentiated elements, as well as their abnormal migration and differentiation.