Genetics research leads to better understanding of children with ACC

Agenesis of the corpus callosum (ACC) is a birth defect in which there is a complete or partial absence of the corpus callosum - the major pathway for communication between the brain’s two hemispheres. It occurs when the corpus callosum fails to develop normally during pregnancy.

Agenesis of the corpus callosum (ACC) is a birth defect in which there is a complete or partial absence of the corpus callosum - the major pathway for communication between the brain’s two hemispheres. It occurs when the corpus callosum fails to develop normally during pregnancy.

ACC
MRI showing complete ACC                         MRI showing partial ACC

ACC is frequent, affecting one in 4,000 newborns, and is common in children with developmental disabilities, affecting 3-5% of children with intellectual disability. It is also a common reason for late-pregnancy termination.

The outcomes for children with ACC range enormously but it is not clear why. Some children attend mainstream school and perform similarly to their peers; these children may not necessarily come to clinical attention. Yet, other children will be severely impaired and will require tailored education in a Special Developmental School environment.  

Collaborating with researchers around the world, MICCN’s Dr Megan Spencer-Smith and team have been investigating genetic causes of ACC as well as mirror movement disorder (where movements in one limb are mirrored by the other limb).

In their unique dataset of families and individuals with mirror movement disorder and/or ACC with no other brain abnormalities, the team discovered that mutations in a specific human gene, called DCC, led to ACC with favourable developmental outcomes. The results suggest that the prenatal detection of ACC without other brain abnormalities related to the DCC mutation indicates a lower risk of an abnormal neurodevelopmental outcome. It is the position of the mutation in the DCC gene determines whether the individual has mirror movement disorder alone, or the combination of ACC and mirror movement disorder, with favourable developmental outcomes.

Given the high frequency of DCC mutations in ACC, the findings will be helpful in a clinical setting to inform prenatal diagnostic and parental counselling for foetuses with ACC. 

Dr Spencer-Smith and her team have planned follow-up studies with these families, and in a larger Melbourne cohort of children with ACC, using neuropsychological, clinical, and neuroimaging data to better understand why some children with ACC perform similarly to their peers and others suffer severe impairments.

Read Dr Spencer-Smith’s full paper, “Mutations in DCC cause isolated agenesis of the corpus callosum with incomplete penetrance”, in Nature Genetics.

For further information on Dr Spencer-Smith’s work in ACC, contact her on t: 03 9905 9148, e: Megan.Spencer-Smith@monash.edu.

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Dr Megan Spencer-­Smith
Pictured: Dr Megan Spencer-Smith

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