Researchers Identify Genetic Cause of Lennox-Gastaut Syndrome
Article published on News-Medical.net
In a recent study, researchers at Baylor College of Medicine and collaborating institutions provided a rare genetic diagnosis in a child with Lennox-Gastaut syndrome, a type of developmental epileptic encephalopathy (DEE) associated with a severe, complex form of epilepsy and developmental delay.
In the study, the team reported the case of a young child with DEE whose previous genomic studies did not provide a genetic diagnosis. Researchers found that a highly complex rearrangement of fragments from certain chromosomes altered the typical organization of genes, leading to a rare condition known as 5q14.3 microdeletion syndrome.
“The child and the family came to Texas Children’s for answers and our team took a closer look at their genome,” said co-author Dr. Hsiao-Tuan Chao. “We reevaluated the child’s genomic condition and found a highly complex reshuffling of chromosomes 3 and 5 resulting in 5q14.3 microdeletion syndrome.”
This reshuffling of chromosomes, or chromothripsis, is a very intricate chromosomal rearrangement. For reasons that are not yet clear, one or several chromosomes can suddenly break down simultaneously into up to thousands of fragments. The cell then pieces the fragments of the chromosomes back together but in a reshuffled order that is different from the original. This reshuffling usually disrupts the normal function of genes in the chromosome fragments, leading to disease. Chromothripsis is more commonly found in cancer; however, this and other studies increasingly support that chromothripsis also is involved in neurodevelopmental disorders. This is the first reported case of specific chromosomes reshuffling leading to a form of DEE due to the disruption of 5q14.3.
The findings highlight the diagnostic importance of identifying chromothripsis in neurological disorders, such as DEE, that are associated with chromosomal alterations. Precise diagnosis is prognostically important because chromothripsis can be associated with increased cancer risk, which may require these individuals to receive enhanced cancer screenings throughout their lives.