What is needed to diagnose of Megalencephaly with ribbon-like heterotopia?
The diagnosis can be suspected on brain imaging features. These features include an abnormally formed gray matter (polymicrogyria-like cortex), an extra band of gray matter (ribbon-like heterotopia), enlarged brain (megalencephaly), and underdeveloped connection between the left and right hemisphere (corpus callosum agenesis). Also enlargement of the fluid-filled cavities of the brain is frequent (ventriculomegaly) sometimes leading to high pressure in the brain (hydrocephalus).
The diagnosis can be confirmed with genetic testing, when a change (mutation) is found in both copies of the EML1 gene.
There are two possible strategies to identify the EML1 changes:
Testing the DNA sequence of multiple genes, including EML1, using a multi-gene panel or exome sequencing.
If the suspicion is high, targeted testing of the EML1 gene is also an option, but this is not available in most genetic laboratories.
The genetic testing can be arranged by a clinical geneticist and involves the collection of a sample of blood or saliva from the affected individual (and possibly the parents). Analysing the DNA of the patient and comparing it with the parents’ DNA may facilitate the detection of the disease-causing changes in the EML1 gene.
Family members
The inheritance of this disorder is autosomal recessive. Usually the parents are healthy and carry a mutation in one copy of the EML1 gene. The change of having another child affected by Megalencephaly with ribbon-like heterotopia is 25%. Healthy siblings can also be a carrier of one mutation.