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

IRF2BPL-related disorders


Other Names:
Neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures; NEDAMSS
IRF2BPL-related 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] IRF2BPL-related 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.
Last updated: 11/27/2018
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]
Last updated: 11/27/2018

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
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
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Last updated: 7/1/2020
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]
Last updated: 11/27/2018
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.
Last updated: 11/27/2018
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]
Last updated: 11/27/2018
IRF2BPL-related disorders are progressive, meaning the symptoms get worse over time.  People with these disorders may lose the ability to walk, talk, and eat.  Over time, they may require placement of a tube into the stomach to aid with feeding as well as a mechanical respirator to help them breath.[1][2] The long-term outlook for people with these disorders is unclear.
Last updated: 11/27/2018
Less than 20 people have been reported in the literature with mutations in the IRF2BPL gene.
Last updated: 11/27/2018

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. 

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  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.