National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Neuronal intranuclear inclusion disease


Other Names:
NIID; Neuronal intranuclear hyaline inclusion disease
Categories:
Neuronal intranuclear inclusion disease (NIID) is a slowly progressive, neurodegenerative disease. NIID may affect any part of the nervous system (central, peripheral, and/or autonomic), as well as various organs.[1] Signs and symptoms may begin anywhere from infancy to late adulthood, and can vary from person to person. In most cases, the disease begins in childhood.[1]

Symptoms of NIID worsen over time and may include dementia, limb weakness, cerebellar ataxia, dystonia, parkinsonism, seizures, and autonomic dysfunction. Therefore, people with NIID may have impairment of balance, movement, cognition, communication, behavior, and the ability to function independently.[1][2] In general, limb weakness and ataxia are more common in children with NIID, while dementia is more common in people diagnosed in adulthood.[1][3]

The features of NIID result from the presence of eosinophilic intranuclear inclusions inside neurons and glial cells (abnormal masses of substances in the nuclei of cells of the nervous system).[2][1][4] Recently, a genetic change in the NOTCH2NLC gene has been found to cause NIID.[5]

Currently there is no treatment that cures or slows the progression of NIID, but medications that help control symptoms may improve quality of life.[3] While the disease is ultimately fatal, life expectancy can range significantly, from one year to several decades after the diagnosis.[1]
Last updated: 2/27/2020

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

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Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Ataxia 0001251
Dysarthria
Difficulty articulating speech
0001260
EMG abnormality 0003457
30%-79% of people have these symptoms
Abnormal form of the vertebral bodies 0003312
Behavioral abnormality
Behavioral changes
Behavioral disorders
Behavioral disturbances
Behavioral problems
Behavioral/psychiatric abnormalities
Behavioural/Psychiatric abnormality
Psychiatric disorders
Psychiatric disturbances
[ more ] 		0000708
Dementia
Dementia, progressive
Progressive dementia
[ more ] 		0000726
EEG abnormality 0002353
Hyperreflexia
Increased reflexes
0001347
Hypertonia 0001276
Nystagmus
Involuntary, rapid, rhythmic eye movements
0000639
Ophthalmoplegia
Eye muscle paralysis
0000602
Scoliosis 0002650
Seizure 0001250
Spina bifida occulta 0003298
5%-29% of people have these symptoms
Abnormality of the pharynx 0000600
Optic atrophy 0000648
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Last updated: 7/1/2020
In many families, neuronal intranuclear inclusion disease (NIID) is caused by a genetic change in the NOTCH2NLC gene.[5] 
Last updated: 2/27/2020
Neuronal intranuclear inclusion disease (NIID) appears to be inherited in an autosomal dominant pattern in families.  In some cases, a person will be the first in their family to develop the condition due to new genetic changes in the NOTCH2NLC gene that result in NIID.[5]   
Last updated: 2/27/2020

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
The differential diagnosis should consider spinocerebellar ataxias, progressive juvenile parkinsonism and dystonia.
Visit the Orphanet disease page for more information.

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • The U.S. National Institutes of Health, through the National Library of Medicine, developed ClinicalTrials.gov to provide patients, family members, and members of the public with current information on clinical research studies. There is a study titled Study of Inherited Neurological Disorders which may be of interest to you.
  • Orphanet lists European clinical trials, research studies, and patient registries enrolling people with this condition. 

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

In-Depth Information

  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Neuronal intranuclear inclusion disease. Click on the link to view a sample search on this topic.

Selected Full-Text Journal Articles

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know.

  1. Sone J, Mori K, Inagaki T, et al. Clinicopathological features of adult-onset neuronal intranuclear inclusion disease. Brain. December, 2016; 139(12):3170-3186. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5382941/.
  2. Lai SC, Jung SM, Grattan-Smith P, et al. Neuronal intranuclear inclusion disease: two cases of dopa-responsive juvenile parkinsonism with drug-induced dyskinesia.. Mov Disord. July 15, 2010; 25(9):1274-1279. https://www.ncbi.nlm.nih.gov/pubmed/20629123.
  3. Fontaine B. Neuronal intranuclear inclusion disease. Orphanet. 2007; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=2289.
  4. Takahashi-Fujigasaki J, Nakano Y, Uchino A, Murayama S. Adult-onset neuronal intranuclear hyaline inclusion disease is not rare in older adults. Geriatr Gerontol Int. March, 2016; Suppl 1:51-56. https://www.ncbi.nlm.nih.gov/pubmed/27018283.
  5. Sone J, Mitsuhashi S, Fujita A, Mizuuchi T et al. Long-read sequencing identifies GGC repeat expansions in NOTCH2NLC associated with neuronal intranuclear inclusion disease. Nature Genet. Aug 2019; 51(8):1215-1221. https://www.pubmed.ncbi.nlm.nih.gov/31332381.