Families

NEDLAAD is the most common disorder linked to changes in the CAPRIN1 gene.

Symptoms:
People with NEDLAAD often have trouble with language development (100% of cases) and may experience intellectual or learning difficulties (83%), ADHD (82%), and autism (67%). Some also show developmental delays (42%) and seizures (33%). Other symptoms can include subtle facial differences, breathing problems, bone and eye abnormalities, hearing loss, and digestive issues.

How rare is it?
So far, only 12 people with NEDLAAD have been described in detail worldwide, making it an ultra-rare condition. However, since CAPRIN1 was only recently added to many genetic testing panels, it’s possible more cases exist but haven't been diagnosed yet.

How is it inherited?
NEDLAAD follows an autosomal dominant inheritance pattern, meaning a change in just one copy of the CAPRIN1 gene can cause the disorder. Most cases happen because of new (de novo) mutations, but in rare instances, the variant has been inherited from a parent who is either mildly affected or appears healthy, suggesting that symptoms can vary even within the same family.

What happens at the gene level?
NEDLAAD is caused by changes that damage or eliminate the function of the CAPRIN1 gene. These include nonsense and frameshift mutations or larger genetic deletions. These changes cause the body to produce only about half the normal amount of CAPRIN1 protein. Some splicing mutations, which interfere with how the gene is read, also lead to loss of function.

CONDCAC is another disorder related to CAPRIN1 but is much rarer.

Symptoms:
The few patients reported brain shrinkage (cerebral or cerebellar atrophy), learning or intellectual disabilities, problems with speech and swallowing (bulbar symptoms), trouble controlling their trunk, poor coordination (ataxia), and muscle weakness. In one patient, other issues were noted as well, like nerve damage, social difficulties, attention problems, scoliosis, and trouble walking.

How rare is it?
Only three cases have been reported worldwide.

How is it inherited?
Like NEDLAAD, CONDCAC is autosomal dominant and usually caused by new (de novo) mutations.

What happens at the gene level?
CONDCAC is linked to a specific change in CAPRIN1, where the amino acid proline at position 512 is replaced by leucine. This likely causes the CAPRIN1 protein to act abnormally (gain-of-function), making it clump together more than it should. Although the exact effect in nerve cells is not fully understood yet, this abnormal behavior is thought to contribute to the disease.