The corpus callosum is the largest tract of nerves in the brain, normally containing about 200 million nerves. It is the largest of five nerve tracts that transfer information between the two sides of the brain. There are various anomalies that can impact the corpus callosum- agenesis (absence) can be total or partial, underdevelopment which is called hypoplasia or maldevelopment which is called dysplasia. Problems with the corpus callosum can occur on its own (isolated) or as part of a broader set of problems. There are numerous syndromes in which corpus callosum disorders are described. The genetic basis for many of these is known. A chromosomal anomaly is found in about 15% and a syndromic cause is identified in about a third of those with a disorder of the corpus callosum. Where a disorder of the corpus callosum is isolated, the cause is less often found.

Until about 5 years ago testing to identify the cause of a corpus callosum disorder involved a detailed chromosome study called a microarray and, if this was normal, sometimes testing of one or few genes was performed if a specific genetic cause was suspected. It is now possible to test all 23,000 genes in one test for about the cost of testing two genes in the past. This means it is now possible to test all genes known to predispose to a problem with the corpus callosum in one test. The three main tests done in this setting are whole genome sequencing (WGS), whole exome sequencing (WES) or a gene panel. In WGS, the approximately 3 billion individual chemicals that make up the human genome are tested whilst in WES, the approximately 50 million chemicals that make up the genes are tested. In a panel test, all the genes known to be involved in disorders of the corpus callosum are tested. This quantum leap forward in technology has meant that a specific diagnosis is now possible in many more people with a disorder of the corpus callosum than was the case as recently as 5 years ago. In addition, new genes involved in disorders of the corpus callosum are regularly being identified. An example of this is the identification of faults in a gene called DCC in a subset of individuals with isolated agenesis of the corpus callosum. This work was a major international collaboration involving teams in Australia (Murdoch Children’s Research Institute), Europe and North America. This was a very important discovery because it is the first gene that has been identified for isolated agenesis of the corpus callosum.

Why is it important to identify the cause of disorders of the corpus callosum? Knowing the cause gives individuals and families answers about why this has occurred which is very important for some. It allows some information about what the future may hold. It enables accurate advice about the chance of future children having a similar condition and options to avoid this if couples wish to do so. This may involve testing embryos created by IVF and only having embryos without the genetic cause transferred to the woman’s uterus, a process called preimplantation genetic diagnosis. The ultimate hope is that by knowing the genetic cause, that specific treatments will be possible to improve the health of the person with the disorder.

Professor Martin Delatycki

Medical Director, Victorian Clinical Genetics Services

Co-Director, Bruce Lefroy Centre, Murdoch Children’s Research Institute