overview
What is NR4A2?
NR4A2 is a gene. It carries the instructions for making a protein called NURR1, which is one of the master switches the brain uses to build and maintain dopamine-producing nerve cells.
the short version
NR4A2 sits on chromosome 2. When it works normally, it tells the right cells in the midbrain to become dopamine neurons and keep producing dopamine across a lifetime.
When one copy of the gene is broken, those instructions are weaker. The downstream effects can include developmental delay, movement differences, seizures in some children, and language delay. The picture varies a lot between children.
my son's picture
My son carries a de novo pathogenic variant in NR4A2 (c.325dup, p.Gln109ProfsTer3), confirmed by trio exome and reported in July 2025 when he was four. He also has an inherited 16p11.2 deletion, so his picture is not NR4A2 alone.
Today he has moderate global developmental delay, autism spectrum disorder level 3, intellectual disability, severe speech apraxia, and ADHD. He sat at 16 months and walked at 19 months. He uses Proloquo2Go to communicate and is starting to string two-word sentences out loud. He has had febrile convulsions but no other seizure types so far. He is bubbly, affectionate, and learns fastest by copying the kids around him.
how rare is this
NR4A2-related syndrome is extremely rare. The largest pooled review so far, Borden et al. 2025, gathered 32 individuals from the whole published literature plus its own new cases. The 2024 Simons Searchlight gene guide put the figure at 27. Those are largely the same people counted again as the literature grows, not two separate groups. The syndrome was first described as a distinct genetic disorder in 2017, so almost every published study is small and every new paper changes the picture.
My son's change, c.325dup, is a duplication of a single letter of DNA rather than a missing or repeated stretch of chromosome. ClinVar classifies it as pathogenic, and I have found one published case carrying the same change, Patient 6 in Singh et al. 2020. That is a count of what has been written up, not a count of how many people carry it.
what we're tracking
Sleep, seizures, behaviour, and milestones, captured as a quick daily note. Patterns matter more than any one day, so the journal stays low-friction on purpose.