Researchers from Baylor College of Medicine, the Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Baylor Genetics, and other collaborating institutions have identified a rare genetic diagnosis in a child with Lennox-Gastaut syndrome. This condition is a type of developmental epileptic encephalopathy (DEE) associated with severe epilepsy and developmental delays.
The study revealed that a complex rearrangement of chromosome fragments 3 and 5 altered gene organization in the q14.3 region of chromosome 5, leading to 5q14.3 microdeletion syndrome. This is the first known case where reshuffling between chromosomes 3 and 5 has resulted in DEE due to this specific disruption. The findings were published in the American Journal of Medical Genetics: Part A.
Dr. Hsiao-Tuan Chao, co-corresponding author and assistant professor at Baylor, explained, “About half of the children with severe epilepsy do not have a diagnosis; there is no explanation for their condition. We wanted to change this situation.” Her lab has been working with Texas Children’s and Baylor Genetics on the Undiagnosed Epilepsy Genetics Initiative to discover new genetic causes for childhood epilepsy.
In this study, researchers examined a young child whose previous genomic studies had not provided a diagnosis. Dr. Chao stated, “The child and the family came to Texas Children’s and the Duncan NRI for answers and our team took a closer look at their genome.” Using advanced sequencing techniques, they identified chromothripsis—a complex chromosomal rearrangement—leading to 5q14.3 microdeletion syndrome.
Chromothripsis involves sudden fragmentation of one or more chromosomes into numerous pieces that are reassembled in an altered order, often disrupting normal gene function. Although typically associated with cancer, recent studies suggest its involvement in neurodevelopmental disorders as well.
Dr. Chao noted that while MEFC2 was not directly affected by this reshuffling, it impacted MEF2C-AS1—a non-coding gene regulating MEFC2 levels—suggesting that its disruption can lead to similar neurological symptoms seen when MEFC2 itself is disrupted.
The study emphasizes the importance of identifying chromothripsis in diagnosing neurological disorders like DEE due to potential links with increased cancer risk requiring enhanced screenings.
Contributors include Melina L. Corriveau, Joshua C. Korb, Sydney L. Michener, Nichole M. Owen, Erica L. Wilson, Jamie Kubala, Alicia Turner, Danielle S. Takacs, Lorraine Potocki, John W. Swann, Mingshan Xue and Hongzheng Dai from institutions such as Baylor College of Medicine and Duncan NRI.
Funding was provided by several foundations including Gordan and Mary Cain Foundation and Burroughs Wellcome Fund.
