GENE GUIDE

CAPRIN1-Related Syndrome

This guide is not meant to take the place of medical advice. Please consult with your doctor about your genetic results and health care choices. This Gene Guide was last updated on 2024. As new information comes to light with new research we will update this page. You may find it helpful to share this guide with friends and family members or doctors and teachers of the person who has CAPRIN1-Related Syndrome.
a doctor sees a patient

CAPRIN1-related syndrome is also called neurodevelopmental disorder with language impairment, autism, and attention deficit hyperactivity disorder or childhood-onset neurodegeneration with cerebellar ataxia and cognitive decline. For this webpage, we will be using the name CAPRIN1-related syndrome to encompass the wide range of variants observed in the people identified.

CAPRIN1-related syndrome happens when there are changes in the CAPRIN1 gene. These changes can keep the gene from working as it should.

Key Role

CAPRIN1 plays a key role in brain development, and new changes in this gene can have a meaningful effect.

Symptoms

Because the CAPRIN1 gene is important for brain activity, many people who have CAPRIN1-related syndrome have:

  • Developmental delay
  • Intellectual disability
  • Language delay
  • Seizures
  • Movement issues, such as tremor, ataxia, or loss of walking
  • Brain changes observed on magnetic resonance imaging (MRI)
  • Autism
  • Anxiety
  • Attention-deficit/hyperactivity disorder (ADHD)
  • Vision issues
  • Scoliosis (sideways curvature of the spine)

CAPRIN1-related syndrome is a genetic condition, which means that it is caused by variants in genes. Our genes contain the instructions, or code, that tell our cells how to grow, develop, and work. Every child gets two copies of the CAPRIN1 gene: one copy from their mother’s egg, and one copy from their father’s sperm. In most cases, parents pass on exact copies of the gene to their child. But the process of creating the egg or sperm is not perfect. A change in the genetic code can lead to physical issues, developmental issues, or both.

Sometimes a spontaneous variant happens in the sperm, egg or after fertilization. When a brand new genetic variant happens in the genetic code is called a ‘de novo’ genetic variant. The child is usually the first in the family to have the genetic variant.

De novo variants can take place in any gene. We all have some de novo variants, most of which don’t affect our health. But because CAPRIN1 plays a key role in development, de novo variants in this gene can have a meaningful effect.

Research shows that CAPRIN1-related syndrome is often the result of a de novo variant in CAPRIN1. Many parents who have had their genes tested do not have the CAPRIN1 genetic variant found in their child who has the syndrome. In some cases, CAPRIN1-related syndrome happens because the genetic variant was passed down from a parent.

Autosomal dominant conditions

CAPRIN1-related syndrome is an autosomal dominant genetic condition. This means that when a person has the one damaging variant in CAPRIN1 they will likely have symptoms of CAPRIN1-related syndrome. For someone with an autosomal dominant genetic syndrome, every time they have a child there is a 50 percent chance they pass on the same genetic variant and a 50 percent chance they do not pass on the same genetic variant.

Autosomal Dominant Genetic Syndrome

GENE / gene
GENE / gene
Genetic variant that happens in sperm or egg, or after fertilization
GENE / gene
Child with de novo genetic variant
gene / gene
Non-carrier child
gene / gene
Non-carrier child

Why does my child have a change in the CAPRIN1 gene?

No parent causes their child’s CAPRIN1-related syndrome. We know this because no parent has any control over the gene changes that they do or do not pass on to their children. Please keep in mind that nothing a parent does before or during the pregnancy causes this to happen. The gene change takes place on its own and cannot be predicted or stopped.

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 CAPRIN1-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 CAPRIN1-related syndrome, the sibling’s risk of having a child who has CAPRIN1-related syndrome depends on the sibling’s genes and their parents’ genes.

  • If neither parent has the same genetic variant causing CAPRIN1-related syndrome, the symptom-free sibling has a nearly 0 percent chance of having a child who would inherit CAPRIN1-related syndrome.

As of 2024, about 13 people with CAPRIN1-related syndrome have been identified in medical research. The first case of this condition was found in 2013.

People who have CAPRIN1-related syndrome may look different. Appearance can vary and can include some but not all of these features:

  • Widely spaced eyes
  • Longer than average face
  • Finger defects

Scientists and doctors have only just begun to study CAPRIN1-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 CAPRIN1-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.

This section includes a summary of information from major published articles and the Simons Searchlight quarterly registry report. It highlights how many people have different symptoms. To learn more about the articles, see the Sources and References section of this guide.

Variants in the CAPRIN1 gene result in either a gain of function OR a loss of function. It is not always obvious what the CAPRIN1 gene variant will do to the CAPRIN1 protein.

Below are two summaries: one for loss-of-function variants and one for gain-of-function variants.

Loss-of-function CAPRIN1 variants

Loss-of-function CAPRIN1 variants are expected to result in a loss of function in the CAPRIN1 protein. The variants could be nonsense, splice site, or insertion/deletion variants that cause either a frame shift or larger gene deletions.

Speech and Learning

Most people with loss-of-function CAPRIN1-related syndrome had developmental delay or intellectual disability, and everyone had language delays or impairment.

  • 10 out of 12 people had developmental delay or intellectual disability (83 percent)
  • 12 out of 12 people had language delays or impairment (100 percent)

Behavior

Many people with loss-of-function CAPRIN1-related syndrome had behavioral challenges, such as autism or attention-deficit/hyperactivity disorder (ADHD).

  • 8 out of 12 people had autism (67 percent)
  • 9 out of 11 people had ADHD (82 percent)
67%
8 out of 12 people had autism.
82%
9 out of 11 people had ADHD.

Brain

Some people with loss-of-function CAPRIN1-related syndrome had seizures. Six out of six people who had brain magnetic resonance imaging (MRI) had a normal result.

  • 4 out of 12 people had seizures (33 percent)
Human head showing brain outline

Other medical findings

Other medical findings included breathing issues, skeletal issues, and eye, hearing, or gastrointestinal issues. Skeletal issues included defects in the curvature of the spine, including scoliosis and kyphoscoliosis. Some people had an abnormally bent or curved fifth finger.

  • 6 out of 12 people had breathing issues (50 percent)
  • 6 out of 12 people had skeletal issues (50 percent)
  • 4 out of 12 people had eye defects (33 percent)
  • 3 out of 12 people had hearing impairment (25 percent)
  • 2 out of 12 people had gastrointestinal issues (17 percent)

Gain-of-function CAPRIN1 variants

Gain-of-function CAPRIN1 variants are expected to result in a gain of function in the CAPRIN1 protein. To date, the only published gain-of-function variant for CAPRIN1 is p.Pro512Leu. The information below is a summary of what is known about this variant.

Speech and Learning

Two people with gain-of-function CAPRIN1-related syndrome had cognitive decline, and language delays or impairment.

  • 2 out of 2 people had cognitive decline
  • 2 out of 2 people had language delays or impairment

Brain

All three people with gain-of-function CAPRIN1-related syndrome had cerebellar atrophy on magnetic resonance imaging (MRI).

Movement

All three people with gain-of-function CAPRIN1-related syndrome developed movement issues between the ages of 10 and 14 years old, and they had lower than average muscle tone. Movement issues included ataxia, instability, and inability to walk.

Where can I find support and resources?

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.”

Sources and references

The content in this guide comes from published studies about CAPRIN1-related syndrome. Below you can find details about each study, as well as links to summaries or, in some cases, the full article.

  • Delle Vedove, A., Natarajan, J., Zanni, G., Eckenweiler, M., Muiños-Bühl, A., Storbeck, M., Guillén Boixet, J., Barresi, S., Pizzi, S., … & Wirth, B. (2022). CAPRIN1P512L causes aberrant protein aggregation and associates with early-onset ataxia. Cellular and Molecular Life Sciences, 79(10), 526. https://pubmed.ncbi.nlm.nih.gov/36136249/
  • Pavinato, L., Delle Vedove, A., Carli, D., Ferrero, M., Carestiato, S., Howe, J. L., Agolini, E., Coviello, D. A., van de Laar, I., … & Brusco, A. (2023). CAPRIN1 haploinsufficiency causes a neurodevelopmental disorder with language impairment, ADHD and ASD. Brain, 146(2), 534-548. https://pubmed.ncbi.nlm.nih.gov/35979925/

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