Researchers Discover Genetic Cause of Chiari Malformation

At the very start of the new year, researchers out of the Washington University in St. Louis shared some exciting medical research: the discovery of two gene variants, associated with brain development, which could lead to the development of Chiari malformation type 1 (“Chiari 1”). As a result, researchers may be able to create new screening, diagnostic, and treatment tools to best serve patients. See the full study findings in the American Journal of Human Genetics.

Chromodomain Genes

668 children with the Chiari 1 malformation enrolled in this study. During the trial, researchers performed whole-exome gene sequencing on these children, as well as 232 family members. Out of these 232, researchers found that 76 also had a previously undiagnosed Chiari malformation. Researchers determined that patients with the Chiari malformation had increased amounts of chromodomain gene mutations, particularly in CHD8 and CHD3. Next, they also determined that Chiari malformation is more common in children with larger heads. If a child’s head is 95% larger than those of peers, there is a 4x higher chance of being diagnosed with Chiari malformation. As a result, researchers suggest to parents to have their children tested if they notice this in their own children.

Next, researchers used zebrafish models to test CHD8 gene changes. They determined that making one gene copy inactive caused an increase in brain size. This suggests that chromodomain genes, which regulate multiple other genes, could play a role in neurodevelopment and neurodevelopmental disorders. Moving forward, additional research is needed.

Chiari Malformation

There are three types of Chiari malformation, a rare condition in which a small or misshapen skull forces brain tissue into the spinal canal. First, type 1 is considered the pediatric form of this condition. It occurs when the skull and brain are still growing. Typically, signs and symptoms of type 1 appear during late childhood or adulthood, and may include:

  • Neck pain
  • Issues with balance and coordination
  • Tinnitus
  • Slow heartbeat
  • Blurry or double vision
  • Hoarse voice
  • Scoliosis
  • Headaches
  • Hand and foot numbness
  • Dizziness
  • Abnormal breathing

The second form, type 2, is congenital and thus present at birth. Typically, more tissue extends into the spinal column in this form. Symptoms include:

  • Arm weakness
  • Difficulty swallowing
  • Rapid eye movements
  • Myelomeningocele

Finally, the third form – type 3 – is the rarest and most severe form. This is also congenital and present at birth. In type 3, part of the cerebellum protrudes through an abnormal opening in the back of the skull. This form is associated with neurological problems and also has the highest mortality rate.

Learn more about Chiari malformation.

Jessica Lynn

Jessica Lynn

Jessica Lynn has an educational background in writing and marketing. She firmly believes in the power of writing in amplifying voices, and looks forward to doing so for the rare disease community.

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