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Disease Profile

IRF2BPL-related disorders

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.

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US Estimated

Europe Estimated

Age of onset

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ICD-10

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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)

Neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures; NEDAMSS

Summary

IRF2BPLrelated disorders are a group of very rare neurodegenerative disorders with neurological symptoms that generally get worse over time. People with these disorders commonly have normal initial development followed by regression and loss of skills.[1][2][3] Symptoms include loss of motor skills (like walking and crawling), loss of speech, abnormal movements, and seizures. These disorders are caused by genetic changes (mutations) of the interferon regulatory factor 2 binding-like (IRF2BPL) gene, which occur for the first time in the affected person.[3] IRF2BPLrelated disorders have been diagnosed through a genetic test known as exome sequencing. There is no treatment for these disorders. Medication and supportive care can help with some of the symptoms. The long-term outlook for people with these disorders is unknown.

Symptoms

There have been fewer than 20 people reported with IRF2BPL-related disorders. Most individuals start out having normal development with normal motor skills and speech. Over time, affected individuals have neurological and developmental symptoms that slowly get worse. Symptoms can include loss of speech, abnormal movements, loss of muscle control, and seizures. Other symptoms include abnormal eye movements, loss of motor milestones (like crawling and walking), and difficulty swallowing. Intellectual ability may or may not be affected. The age of onset of symptoms ranges from early childhood to adulthood.[1][2][3]

The severity of symptoms seems to be related to the type of mutation found in the IRF2BPL gene. Gene mutations that result in a short non-working protein (nonsense mutations) seem to lead to more severe symptoms than other types of mutations.[2]

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
Percent of people who have these symptoms is not available through HPO
Autosomal dominant inheritance
0000006
Cerebellar atrophy
Degeneration of cerebellum
0001272
Cerebral atrophy
Degeneration of cerebrum
0002059
Choreoathetosis
0001266
Corpus callosum atrophy
0007371
Developmental regression
Loss of developmental milestones
Mental deterioration in childhood

[ more ]

 0002376
Dysarthria
Difficulty articulating speech
0001260
Dysmetria
Lack of coordination of movement
0001310
Dysphagia
Poor swallowing
Swallowing difficulties
Swallowing difficulty

[ more ]

 0002015
Dystonia
0001332
Esotropia
Inward turning cross eyed
0000565
Generalized hypotonia
Decreased muscle tone
Low muscle tone

[ more ]

 0001290
Global developmental delay
0001263
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

 0001249
Loss of speech
0002371
Nystagmus
Involuntary, rapid, rhythmic eye movements
0000639
Progressive
Worsens with time
0003676
Seizure
0001250
Spasticity
Involuntary muscle stiffness, contraction, or spasm
0001257
Weakness of facial musculature
Decreased facial muscle strength
Decreased strength of facial muscles
Face weakness
Facial muscle weakness
Facial weakness
Reduced facial muscle strength
Weakness of face

[ more ]

 0030319

Cause

IRF2BPL-related disorders are caused by mutations (genetic changes) in the IRF2BPL gene. The protein made by this gene is found in many different organs, including the brain. It is unclear how the protein made by this gene works in the body and why changes in the gene result in these disorders. The IRF2BPL protein may be involved in the regulation and function of other genes.[3]

Diagnosis

These disorders are diagnosed based on symptoms and by genetic testing. IRF2BPL-related disorders are diagnosed by at type of genetic testing known as exome sequencing.[1] Exome sequencing is a technology that allows doctors and researchers to study many different genes at the same time. Exome sequencing involves searching the genetic code for mistakes that change how the protein-making parts of a gene work.

Treatment

The treatment for people with IRF2BPL-related disorders is focused on treating specific symptoms. Seizures associated with IRF2BPL gene mutations have been reported as being difficult to control with medication.[1][2]

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.

Social Networking Websites

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

  • 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. 

References

  1. Marcogliese PC, Shashi V, Spillmann RC, Strong N et al. IRF2BPL is associated with neurological phenotypes. Am J Hum Genet. Sep 2018; 103(3):245-260. www.ncbi.nlm.nih.gov/pubmed/30057031.
  2. Tran Mau-Them F, Guibaud L, Duplomb L, Keren B et al. De novo truncating variants in the intronless IRF2BPL are responsible for developmental epileptic encephalopathy. Genet Med. Aug 2018; epub:https://www.ncbi.nlm.nih.gov/pubmed/30166628.
  3. Interferon regulatory factor 2-binding protein like; IRF2BPL. Online Mendelian Inheritance in Man. Updated Oct 2018; https://www.omim.org/entry/611720. Accessed 11/15/2018.
  4. Shelkowitz E, Singh JK, Larson A, Elias ER. IRF2BPL gene mutation: Expanding on neurologic phenotypes. Am J Med Genet A. 2019; 179(11):2263-2271. https://pubmed.ncbi.nlm.nih.gov/31432588.

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