Gain-Of-Function Variants In The ODC1 Gene Cause A Syndromic Neurodevelopmental Disorder Associated With Macrocephaly, Alopecia, Dysmorphic Features, And Neuroimaging Abnormalities

The study identified a syndromic neurodevelopmental disorder linked to gain-of-function variants in the ODC1 gene, affecting four patients. This disorder was characterized by global developmental delay, alopecia, macrocephaly, and distinct facial features. Neuroimaging showed various abnormalities, including issues with white matter and the corpus callosum. Elevated levels of N-acetylputrescine were found in plasma, suggesting a metabolic component. Potential treatments could involve ODC1 inhibitors and dietary changes to manage polyamine levels. Given the ODC1 gene's association with cancer, ongoing cancer surveillance might be necessary for affected individuals.