Understanding Chiari Type 1 Malformations in Children

About one in 100 children has a common brain disorder called Chiari 1 malformation, except most of the children with this will not be suspected of brain malfunction. For those who do experience this disorder, 1 in 10 of the kids with this disorder will experience headaches, neck pain, hearing, vision and balance disturbances, or other neurological symptoms. The condition occurs when the lowest parts of the brain are lower than the base of the skill.

Little is understood about the genetic alterations that contribute to this disease besides it may be passed down genetically. “In new research, scientists at Washington University School of Medicine in St. Louis has shown that Chiari 1 malformation can be caused by variations in two genes involved in brain development” (Henderson).

chiari malformations

This condition can cause frequent ringing headaches, pain, abnormal sensations or loss of, or weakness and most of the time the person does not realize this is from the Chiari. If a person is looking to fix the Chiari disorder they would need brain surgery, which may not be appealing to most patients.

To identify genes that cause Chiari 1 malformation, Haller and colleagues sequenced all the genes of 668 people with the condition, as well as 232 of their relatives. Of these relatives, 76 also had Chiari 1 malformation and 156 were unaffected. The research team included first author Brooke Sadler, PhD, an instructor in pediatrics, and co-authors David D. Limbrick, Jr., MD, PhD, a professor of neurosurgery and director of the Division of Pediatric Neurosurgery, and Christina Gurnett, MD, PhD, a professor of neurology and director of the Division of Pediatric and Developmental Neurology, among others. (Henderson)

Genetic sequencing showed that those with the Chiari 1 malformation were significantly more likely to carry mutations in their chromodomain genes. Several of these mutations were de novo, meaning that the mutation occurred during fetal development and the same mutation was not found in their relatives.

chiari malformations doctor

It was particularly the CHD3 and CHD8 chromodomain genes which included numerous variants that are associated with the malfunction. It was shown in research done on tiny zebrafish that the CHD8 is responsible for regulating brain size.

Chromodomain genes help control access to large strands of DNA, therefore regulating expression of entire gene sets. Variations in chromodomain gene sequencing have been known to cause conditions such as autism spectrum disorders, developmental delays, and unusually large or small heads.

These findings were published Dec. 21 in the American Journal of Human Genetics, which could lead to new ways of identifying those with the Chiari 1 malformations.

Sadler, B., et al. (2020) Rare and de novo coding variants in chromodomain genes in Chiari I malformation. American Journal of Human Genetics. doi.org/10.1016/j.ajhg.2020.12.001.

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