Megalencephaly (or macrencephaly; abbreviated MEG) is a growth development disorder in which the brain is abnormally large. It is characterized by a brain with an average weight that is 2.5 standard deviations above the mean of the general population. Approximately 1 out of 50 children (2%) are said to have the characteristics of megalencephaly in the general population.A mutation in the PI3K-AKT pathway is believed to be the primary cause of brain proliferation and ultimately the root cause of megalencephaly. This mutation has produced a classification of brain overdevelopment that consists of two syndromes including megalencephaly-capillary malformation (MCAP) and megalencephaly-polydactyly-polymicrogyria-hydrocephalus (MPPH). Megalencephaly is usually diagnosed at birth and is confirmed with an MRI. There are several neuropsychiatric disorders linked with megalencephaly; however, studies have shown that autism is the most prevalent association with the malformation of MEG. Although no treatment currently exists for megalencephaly, management methods are focused at reducing deficits linked with autism. Most recent research is targeted at creating inhibitors to reduce the mutational pathway that causes megalencephaly. Classification
Macrocephaly
Macrocephaly is a term used to refer to a person who has an abnormally large head. The circumference of the head must be above the 95th percentile or at least 2.5 standard deviations from the mean of normal weight and gender groups in the United States. A person with macrocephaly does not necessarily indicate that megalencephaly is also present. Large skulls usually exhibit no neurodevelopment conditions at all, meaning most individuals with macrocephaly are healthy.
However, there is no definitive evidence that autism is the primary cause/result of megalencephaly.Since most children with megalencephaly also have autism, the goal of treatment for MEG is focused on managing the signs and symptoms associated with autism. Other associations
Achondroplasia
Beckwith–Wiedemann syndrome
Neurofibromatosis type I (NF1)
Tuberous sclerosis (TS)
Klippel–Trénaunay syndrome
Epidermal nevus syndrome

Causes
Although very little is still known as to the direct cause of megalencephaly, recent studies have begun to provide early indications of possible sources for its formation. Recent research has shown that there is a strong link between genetic pathways that cause brain develop and mutations in that pathway that result in brain overgrowth. PI3K-AKT
Recent studies have shown that mutations in phosphoinositide 3-kinase (PI3K) and AKT (also known as protein kinase B) pathway have been identified in MCAP and MPPH. This pathway has proven to be an integral part of brain growth and development and is an area of interest to many researchers who study the cause of megalencephaly. Mutations in this pathway have been shown to cause a gain of function in the activation of the PI3K-AKT pathway. This cellular pathway is critical in the regulation of diverse cell functions including, cell growth, proliferation, metabolism, survival, apoptosis, angiogenesis, tumorigenesis and most importantly in regards to megalencephaly, brain development. AKT is a crucial signaling molecule part of the PI3K pathway and is also involved in many cellular functions. These functions include, brain development, synaptic plasticity and neurodevelopment. Loss of function in AKT can cause microcephaly in humans while inactivation of the pathway can cause hemimegalencephaly.