About HNRNPH2

What is HNRNPH2 (H2)?

HNRNPH2-Related Neurodevelopmental Disorder (H2-RNDD) is a genetic condition caused by a change (variant) in the HNRNPH2 gene.
Also called Bain type syndromic intellectual disability or X‑linked syndromic neurodevelopmental disorder.
The HNRNPH2 gene helps with processing genetic messages (RNA) used in making proteins important for brain development.

The disorder is usually caused by a new (de novo) change in the HNRNPH2 gene — meaning it was not inherited from the parents.
- We do know of a few inherited cases where the parent is unaffected.
It follows an X‑linked pattern, so:
- Girls may have one changed copy and one working copy of the gene.
- Boys have only one X chromosome, so effects can be more variable.

Developmental delay: slow progress in motor milestones (sitting, walking) and learning.
- Many individuals have been given a dual diagnosis of cerebral palsy.
Intellectual disability: ranging from moderate to severe.
Language delays: many children are minimally verbal or nonverbal.
Muscle tone abnormalities: low (hypotonia) or high (hypertonia) tone.
Behavioral/psychiatric issues: anxiety, attention problem, and autistic features.
Seizures: occur in some individuals.
- Estimated in approximately one third of individuals.
- Usually starting around age seven.
- Usually well controlled with medication.
Other common features:
- Feeding difficulties or poor growth.
- Gastrointestinal issues (e.g., constipation).
- Vision differences (like strabismus and cortical visual impairment).
- Orthopedic concerns (scoliosis, hip issues).

Clinical evaluation + genetic testing that finds a pathogenic (harmful) variant in the HNRNPH2 gene confirms diagnosis.

There’s no cure, but many therapies help improve skills and quality of life:
- Physical therapy (movement, strength)
- Occupational therapy (daily living skills)
- Speech and communication therapy
- Behavioral support and psychiatric care when needed
- Medical care for seizures, feeding issues, sleep concerns
Our team at Columbia University is currently treating eight individuals with H2-RNDD with an experimental precision therapeutic in collaboration with the n-lorem foundation using antisense oligonucleotide (ASO) technology.
For more information, see presentations here:
- https://www.nlorem.org/nano-rare-patient-colloquium-2025/ (Investigator Presentation Day One Expert Panel and Day Two Investigator Presentation Neurodevelopmental Disorder)
- https://www.nlorem.org/rosies-story-a-nano-rare-treatment-pioneer/
- https://www.nlorem.org/ultimate-auction/anais-spectrum-of-love/

Most clinical concerns are within the first six months of life.
An early diagnosis can provide understanding to "why" and starting targeted therapies.
The exact symptoms and severity vary widely between individuals.
Many affected people need ongoing support through childhood and adulthood.

As soon as you read this page, please join more families affected by H2-RNDD by visiting Yellow Brick Road Project.
Consider joining our research project by emailing Dr. Jennifer Bain directly at jb3634@cumc.columbia.edu.
- Our research project is ethics board approved by Columbia University Irving Medical Center.
  - See our clinical trials posting here.
- You can contribute by emailing a genetic report and providing some clinical information (no in-person evaluations required).
- We are enrolling those in the United States and internationally.
- We co-host research family meetings with Yellow Brick Road Project both nationally and internationally every year.
- We are happy to evaluate you clinically at our hospital practice in NYC!
Consider joining Simon Searchlight to contribute to a larger research study, which we can also access for data collection.