Scientists studying the largest brain ever recorded in a child, have discovered a genetic defect which causes a rare disease linked to overgrowth, autism and epilepsy.

An international team of researchers from the University of Sussex’s Genome Damage and Stability Centre, England and the Centre for Integrative Brain Research at Seattle Children’s Hospital in the United States, have discovered multiple defects in a gene called AKT3, which causes a condition which results in dramatic brain overgrowth.

As part of the study, the scientists studied the brains of people who had suffered from brain overgrowth (or megalencephaly) and focal cortical malformations, the symptoms of which cause abnormal brain development. Research was undertaken on patients from the UK, Canada, Italy and the US, including a now deceased six year-old from the US, whose brain was found to be almost twice the normal size and is the largest child’s brain ever recorded by scientists.

The scientists discovered the disease, which can cause therapy resistant epilepsy and autism in some people, is triggered by multiple defects in the AKT3 gene, a gene more commonly mutated in cancers such as breast and prostate cancer.

The scientists also discovered that within people suffering from these brain disorders, the affected brains and different brain regions might contain different amounts of mutated cells. This is a phenomenon known as a ‘genetic mosaicism’, which makes it extremely difficult for scientists to accurately genetically diagnose people with the condition.

Following the study, the team now believe current cancer drugs on the market could potentially be used to treat inherited brain overgrowth syndromes associated with epilepsy possibly reducing the need for such patients to undergo complex brain surgery.

Professor Mark O’Driscoll, from the University of Sussex’s Genome Damage and Stability Centre, said:  “We have uncovered a fascinating group of different mutations in the AKT3 gene which is a vital step towards being able to treat this devastating disease. 

“It is now crucial that scientists work to ascertain whether certain pre-existing cancer drugs, originally designed to turn the AKT3 gene off, could be used to treat this devastating condition.”

Dr. Ghayda Mirzaa, from the Centre for Integrative Brain Research at Seattle Children’s Hospital said: “Advances in genetic technologies now allow us to detect genetic changes that occur in only a small number of cells and tissues affected by disease, facilitating the discovery of the genetic changes in AKT3.

The identification of genetic changes in this critical gene in conditions causing childhood overgrowth, epilepsy and autism is a crucial first step towards exploring potential therapies for these disorders in the future”

The paper entitled, ‘Activating mutation of AKT3 are associated with a spectrum of brain malformations including extreme megalencephaly, focal malformations of cortical development and autism’ has been published in BRAIN, a neurology journal, published by Oxford University Press and can be found here.