RNU4-2-Related Syndrome

RNU4-2-related syndrome happens when there are changes in the RNU4-2 gene. These changes can keep the gene from working as it should.

Each family is different. A geneticist or genetic counselor can give you advice on the chance that this will happen again in your family.

The risk of having another child who has RNU4-2-related syndrome depends on the genes of both biological parents. 

• If neither biological parent has the same genetic variant found in their child, the chance of having another child who has the syndrome is on average 1 percent. This 1 percent chance is higher than the chance of the general population. The increase in risk is due to the very unlikely chance that more of the mother’s egg cells or the father’s sperm cells carry the same genetic variant. 
• If one biological parent has the same genetic variant found in their child, the chance of having another child who has the syndrome is 50 percent. 

For a symptom-free brother or sister of someone who has RNU4-2-related syndrome, the sibling’s risk of having a child who has RNU4-2-related syndrome depends on the sibling’s genes and their parents’ genes. 

• If neither parent has the same genetic variant causing RNU4-2-related syndrome, the symptom-free sibling has a nearly 0 percent chance of having a child who would inherit RNU4-2-related syndrome. 
• If one biological parent has the same genetic variant causing RNU4-2-related syndrome, the symptom-free sibling has a 50 percent chance of also having the same genetic variant. If the symptom-free sibling has the same genetic variant, their chance of having a child who has the genetic variant is 50 percent. 

For a person who has RNU4-2-related syndrome, the risk of having a child who has the syndrome is about 50 percent.

As of 2026, over 200 people with RNU4-2-related syndrome have been described in the medical research.

People with RNU4-2-related syndrome may look different. Appearance can vary and can include, but is not limited to, these features:

• Deep-set eyes
• Vertical fold of skin that covers the inner corner of the eye
• Noticeable nasal bridge
• Nostrils that face forward
• Short distance between the lip and the upper lip and the nose
• Full lips
• Large tongue
• Full cheeks
• Large ears

Scientists and doctors have only just begun to study RNU4-2-related syndrome. At this point, there are no medicines designed to treat the syndrome. A genetic diagnosis can help people decide on the best way to track the condition and manage therapies. Doctors can refer people to specialists for:

• • Physical exams and brain studies
  • Genetics consults
  • Development and behavior studies
  • Other issues, as needed

A developmental pediatrician, neurologist, or psychologist can follow progress over time and can help:

• • Suggest the right therapies. This can include physical, occupational, speech, or behavioral therapy.
  • Guide individualized education plans (IEPs).

Specialists advise that therapies for RNU4-2-related syndrome should begin as early as possible, ideally before a child begins school.

If seizures happen, consult a neurologist. There are many types of seizures, and not all types are easy to spot. To learn more, you can refer to resources such as the Epilepsy Foundation’s website: www.epilepsy.com/learn/types-seizures.

Learning and Speech

Most people with RNU4-2-related syndrome had developmental delay or intellectual disability, and speech delay or impairment.

• 133 out of 134 people had developmental delay (99 percent)
• 112 out of 112 people had intellectual disability (100 percent)
• 108 out of 116 people had speech impairment (93 percent)

The severity of intellectual disability varied among people:

• 8 out of 112 people had mild intellectual disability (7 percent)
• 31 out of 112 people had moderate intellectual disability (28 percent)
• 73 out of 112 people had severe intellectual disability (65 percent)

Language ability varied among people:

• 8 out of 116 people had regular communication (7 percent)
• 16 out of 116 people spoke in simple sentences (14 percent)
• 31 out of 116 people spoke in few words (27 percent)
• 61 out of 116 people were non-verbal (53 percent)

Behavior

People with RNU4-2-related syndrome had behavioral issues, such as features of autism, repetitive behaviors (stereotypic behavior), and sleep challenges. People with RNU4-2-related syndrome were happy, friendly, and affectionate. Families reported a love for music and water play.

• 52 out of 92 people had autism (57 percent)
• 70 out of 90 people had stereotypic behavior (78 percent)

Brain

People with RNU4-2-related syndrome had seizures, including infantile epileptic spasms syndrome, febrile seizures, generalized tonic-clonic seizures, absence seizures, and focal seizures. The age of seizure onset occurred around 3 years, with Pa range of onset between birth to 13 years old. About 1 in 10 people developed refractory seizures.

• 81 out of 140 people had seizures (58 percent)

The frequency of seizures varied among people:

• 4 out of 56 people had seizures daily (7 percent)
• 5 out of 56 people had seizures weekly (9 percent)
• 13 out of 56 people had seizures monthly (23 percent)
• 23 out of 56 people had seizures yearly (41 percent)
• 11 out of 56 people had seizures less often than 1 time a year (20 percent)

People with RNU4-2-related syndrome had brain changes seen on magnetic resonance imaging (MRI), lower than average muscle tone (hypotonia), and a smaller than average head size (microcephaly).

• 107 out of 130 people had brain changes seen on MRI (82 percent)
• 88 out of 138 people had hypotonia (64 percent)
• 97 out of 141 people had microcephaly (69 percent)

Heart

A few people with RNU4-2-related syndrome had congenital heart defects, such as atrial septal defect, ventricular septal defect, bicuspid aortic valve, mitral regurgitation, and arrhythmias.

• 21 out of 112 people had congenital heart defects (19 percent)

Vision and hearing

People with RNU4-2-related syndrome had vision issues, such as crossed eyes (strabismus) or eyes that move rapidly without control (nystagmus). Some had issues with hearing.

• 70 out of 124 people had vision issues (57 percent)
• 37 out of 124 people had crossed eyes (30 percent)
• 9 out of 125 people had hearing loss (7 percent)

Feeding and gastrointestinal

People with RNU4-2-related syndrome had feeding issues, failure to thrive, and constipation. Many people were drooling as children and young adults.

• 80 out of 125 people had feeding issues (64 percent)
• 65 out of 126 people had failure to thrive (52 percent)
• 63 out of 123 people had feeding difficulties (51 percent)

Growth

About 1 in 3 had intrauterine growth restriction, and many children that were born within a typical growth range had a slow down in growth over time. Half of people had short height (short stature). Some people had low bone density or stress fractures.

• 72 out of 140 people had short stature (51 percent)

Simons Searchlight

Simons Searchlight is an online international research program, building an ever growing natural history database, biorepository, and resource network of over 175 rare genetic neurodevelopmental disorders. By joining their community and sharing your experiences, you contribute to a growing database used by scientists worldwide to advance the understanding of your genetic condition. Through online surveys and optional blood sample collection, they gather valuable information to improve lives and drive scientific progress. Families like yours are the key to making meaningful progress. To register for Simons Searchlight, go to the Simons Searchlight website at www.simonssearchlight.org and click “Join Us.”

• Learn more about Simons Searchlight – www.simonssearchlight.org/frequently-asked-questions
• Simons Searchlight webpage with more information on RNU4-2 – www.simonssearchlight.org/research/what-we-study/rnu4-2