What is the RORA gene?

RORA (retinoic acid-related orphan receptor alpha) is a gene that produces a protein that helps regulate the activity of other genes. It plays a key role in brain development, especially in the cerebellum, which is responsible for coordination and balance. The RORA gene also supports neurological health by helping protect neurons from stress and inflammation.

What happens when there’s a change in the RORA gene?

Certain rare pathogenic variants in RORA disrupt its normal function. These changes can interfere with brain development and lead to a condition known as RORA-related neurodevelopmental disorder. This rare condition is caused by variations in a single copy of the gene (autosomal dominant) and has been observed in multiple unrelated families around the world. It can occur de novo, which means it is non-inherited.

What are the symptoms of a RORA-related disorder?

Research has shown that RORA-related variants can lead to:

• Delays in walking and talking
  Children often reach developmental milestones later than typical — many walk after age 2 or have significant speech delays.

• Intellectual disability and autism-like traits
  Many individuals have learning challenges and features consistent with autism spectrum disorder (ASD), such as difficulty with social interaction or communication.

• Epileptic seizures
  About half of reported individuals with RORA variants have seizures, often generalized or myoclonic (sudden muscle jerks).

• Poor coordination (ataxia)
  Most individuals have signs of cerebellar dysfunction, including unsteady walking, low muscle tone, or balance issues. MRI scans often show underdevelopment (hypoplasia) or shrinkage (atrophy) of the cerebellum, especially in the midline region called the vermis.

• Differences in severity and timing
  No two people are exactly alike. Some experience mild delays, while others face more complex challenges. Symptoms may appear early in life, emerge later, or evolve over time.

These symptoms have been observed in some individuals or are biologically plausible, but current evidence is more limited and ongoing research is needed to confirm how common or directly connected they are.

• ADHD and executive function challenges
  Some individuals with RORA variants show signs of inattention, hyperactivity, or difficulty with impulse control. RORA is expressed in brain regions involved in attention and regulation, and some genetic studies have linked RORA to ADHD-related pathways. However, specific clinical data on ADHD diagnoses in RORA patients remain limited, and more research is needed to confirm this association.

• Emotional dysregulation and behavioral challenges
  Families and clinicians have reported mood swings, frustration, or difficulty managing emotions in some individuals. While these may overlap with features of autism or ADHD, they are not yet systematically studied in RORA-related cases.

• Sensory processing differences
  Some individuals may be unusually sensitive to sound, touch, or visual stimuli, but these symptoms have only been reported anecdotally so far. The cerebellum, which is affected in RORA-related disorders, is known to play a role in integrating sensory input, suggesting a possible biological link that requires further investigation.

• Sleep disturbances
  RORA helps regulate circadian rhythms — the body’s natural sleep-wake cycle. In animal and cellular studies, changes in RORA activity have been linked to disrupted sleep patterns. While sleep problems have been reported in other conditions involving RORA dysfunction (including autism), direct evidence in individuals with RORA-related disorder is currently limited.

Why does research into RORA matter?

Although there is currently no cure, ongoing research is uncovering how RORA functions in the brain and what might go wrong when it’s disrupted. Preclinical studies are exploring potential treatments that could one day enhance RORA activity or protect neurons, offering hope for future therapies.

As researchers learn more, they aim to answer key questions:

• How does RORA shape brain development at different stages?

• Why do symptoms vary so much between individuals?

• What therapies could make a meaningful difference?

Understanding RORA is not only helping affected individuals and families — it’s also shedding light on broader mechanisms in autism, epilepsy, and brain health.