Rare Hematology News

Disease Profile

Neuronal intranuclear inclusion disease

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

Childhood

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ICD-10

G31.0

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

NIID; Neuronal intranuclear hyaline inclusion disease

Categories

Congenital and Genetic Diseases; Nervous System Diseases

Summary

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]

Symptoms

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.

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
1%-4% of people have these symptoms
CSF pleocytosis
0012229
Decreased motor nerve conduction velocity
0003431
Decreased sensory nerve conduction velocity
0003448
EMG: decremental response of compound muscle action potential to repetitive nerve stimulation
0003403
Episodic vomiting
0002572
Increased CSF protein
0002922
Leukoencephalopathy
0002352
Loss of consciousness
Passing out
0007185
Miosis
Constricted pupils
Pupillary constriction

[ more ]

0000616
Muscle weakness
Muscular weakness
0001324
Rigidity
Muscle rigidity
0002063
Syncope
Fainting spell
0001279
Tremor
0001337
Urinary incontinence
Loss of bladder control
0000020
Ventriculomegaly
0002119
Percent of people who have these symptoms is not available through HPO
Autosomal dominant inheritance
0000006
Gait disturbance
Abnormal gait
Abnormal walk
Impaired gait

[ more ]

0001288
Hyporeflexia
Decreased reflex response
Decreased reflexes

[ more ]

0001265
Sensory impairment
0003474

Cause

In many families, neuronal intranuclear inclusion disease (NIID) is caused by a genetic change in the NOTCH2NLC gene.[5]

Organizations

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

    Learn more

    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

        References

        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; https://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.

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