Rare New Genetic Disorder Identified

Through the use of a national network and gene mapping tools, researchers were able to identify a new and unnamed genetic disorder.

The disorder first came to light when a 3-year-old boy with mild developmental delays and physical characteristics, including a large body and head circumference, showed up at Duke University School of Medicine.

Vandana Shashi, the child’s physician and a professor of pediatrics for the Division of Medical Genetics at Duke, underwent a journey to solve this mysterious medical case, according to a press release. In an attempt to solve the case, Shashi used the tools of the Undiagnosed Diseases Network (UDN), which links Duke and 6 other medical teaching sites around the country that pool information and innovations about rare and unexplainable diseases.

After conducting a genetic analysis, researchers found a mutation of the gene ASXL3, which has never before been singled out as a cause of a disease. After connecting with other UDK research labs and an international database of genes and disease characteristics called GeneMatcher, researchers were able to find 5 additional children who had the same physical features and the ASXL2 gene mutation, within 6 weeks.

The findings were published in the American Journal of Human Genetics.

“We can now definitely say this is a newly identified disease. With just 1 case, we could not say the gene mutation was the underlying cause,” Shashi said. “But with 6 cases, all with the same ASXL2 mutation, it is definitive.”

The new disease shares similarities to 2 other rare genetic disorders, called Bohring-Opitz syndrome and Bainbridge-Ropers syndrome, which both arise from related genes. Bohring-Opitz syndrome develops as a result of a mutation of the ASXL1 gene, while Bainbridge-Ropers syndrome is caused by a flaw in the ASXL3 gene.

Although it remains unknown how the ASXL2 genetic mutation occurs, researchers noted that identifying the root cause of the children’s condition is the first step. Furthermore, it may help to drive the development of new treatment approaches and options.

However, there is some immediate benefit for the families of the children.

“It has been wonderful to be connected to other families who share this genetic condition,” said Teresa Locklear, mother of Isaac, who was the first patient to present with the mutation at Duke, in a press release. “When we started, we hoped we would find other families with children who were older than Isaac, to provide a sort of roadmap for what to expect. But it turns out, Isaac is the oldest and we are the ones sharing our experiences with parents of younger children, and that’s been so rewarding.”

Researchers noted that building a community of families with rare diseases and reducing isolation has had an incredible impact.

“These families feel truly alone when their child clearly has a disorder, and yet there is no name for it, and no community of people they can relate to with shared experiences,” said study co-author Loren del Mar Peña. “This will help them be able to connect with others and compare notes. That’s a huge deal — to know you aren’t the only one and there a[re] 5 other children out there.”