HNRNPH2-related Disorders

What is HNRNPH2?

Variations in the HNRNPH2 gene have recently been described in association with tone abnormalities, developmental delay, intellectual disability, autism, and seizures. The condition is genetic and the gene is on the X chromosome. We are still trying to understand why mutations in HNRNPH2 cause neurological problems, but we know that it has something to do with a problem with how genes are expressed within cells. HNRNPH2 encodes a protein HNRNPH2 that helps gene messages move inside the cell. Research suggests that this protein is important during development of the brain before birth.  In the brain, we assume that this protein is important for brain development.  We think that abnormalities in this protein can lead to problems with brain development.

The mutations found in the individuals we have studied are “de novo” or “new” in the individual with symptoms.  None of their parents or siblings have abnormalities in the HNRNPH2 gene, and they are the first individual with this genetic variant in their family.

The variants we have reported are located in a specific location within the protein at amino acids 206 (nucleotides 616 and 617) and 209 (nucleotide 629). We are still in the early days of studying HNRNPH2 and we may find that genetic changes in other parts of the protein could also lead to neurodevelopmental issues.

What We Know:

The 6 individuals that we have identified to have abnormalities in this gene, all have developmental delay or intellectual disability. Other neurological problems include all with changes in their muscle tone (the passive movement of a person’s muscles) and many with seizures.  Interestingly, several of the individuals also have psychiatric illnesses such as anxiety and 3 of the 6 individuals also have a diagnosis of autism spectrum disorder (ASD).  Variants in HNRNPH2 also seem to affect other organ systems in the body aside from the brain.  For example, patients with HNRNPH2 mutations also have problems with growth, gastroesophageal reflux disorder, scoliosis and other skeletal problems, heart problems and typical facial features.  We are not sure if there is any association with neurodegeneration.

For more information, please look at our publication on a group of families with this condition and the scientific background.

What We Don’t Know

While we learn more about every new person with this condition, there is still a lot to learn. If you are a parent or family member of someone with a HNRNPH2 genetic variant or if you are a clinician or researcher working with a patient with this condition, we would love to learn from you. We believe that families, clinicians, and researchers all working together and sharing our experiences, will benefit everyone.

What We’re Doing

We are working on studies to try to better understand this condition.  Hopefully with more information and a better understanding of HNRNPH2 we can support individuals with this condition better. We are trying to understand what the gene change does in the brain and how it affects behavior and brain function.

We invite families with HNRNPH2 variants to help us improve our understanding by contacting us and partnering. We need to better understand why changes in HNRNPH2 causes problems with brain function so we can develop new treatments.