CIC-related neurodevelopmental disorder is a condition caused by mutations in the CIC gene, which provides instructions for making the CIC protein. This protein plays a crucial role in brain development, especially in helping brain cells mature and function properly. When mutations occur in the CIC gene, brain development can be disrupted, leading to challenges such as developmental delays, intellectual disabilities, autism spectrum disorder (ASD), seizures, and attention deficit hyperactivity disorder (ADHD).

Previous research has described several cases of patients with CIC mutations who show a range of neurobehavioral difficulties. However, not all mutations have the same effects—some changes in the gene produce harmful (pathogenic) versions of the CIC protein, while others may not cause problems.

This new study identifies a pathogenic CIC mutation that had not been reported before. What makes this study especially interesting is that it follows a family across two generations—a mother and her two children— who all carry the same CIC mutation, but show very different symptoms.

The daughter has autism, ADHD, developmental delay/intellectual disability, and severe seizures.

The son also has ADHD, developmental delay/intellectual disability, and moderate seizures.

The mother, who carries the same mutation, experiences mild seizures but has normal thinking and learning abilities.

All three family members have been treated with various seizure medications, but their responses and the severity of their seizures differ significantly.

This study highlights an important fact: even with the exact same genetic mutation, the symptoms and severity of CIC-related neurodevelopmental disorder can vary widely between individuals. This suggests that other factors—such as additional genetic differences or environmental influences—may change how the disease appears and progresses. Scientists call this the modifier effect.

Currently, researchers don’t yet know what these additional factors are. But as more cases are discovered and studied, scientists hope to better understand these influences. This knowledge could lead to more personalized treatments and improved care for people affected by CIC-related neurodevelopmental disorder.

Reference:

Kishnani S. et al. Phenotypic Variability of an Inherited Pathogenic Variant in CIC Gene: A New Case Report in Two-Generation Family and Literature Review. Journal of Pediatric Neurology (2020). Link to the original article.