Skip to main content

IRF2BPL

IRF2BPL



Overview

Interferon regulatory factor 2 binding protein-like–related disorder (IRF2BPL–related disorder) is a very rare genetic condition. IRF2BPL refers to a gene that helps the brain and nervous system work properly.  

Symptoms typically begin in childhood. Symptoms can start as early as the first 6 months of life. They can include: 

Extra movements that can appear shaky, wiggly, dance-like, twisting, or stiff 

Trouble controlling movements 

Seizures 

Loss or failure to attain developmental skills  

This is a rare disorder. Experts are still learning about all the different symptoms that may be associated with it.

A mutation is a change in a gene that causes it to not work properly. Mutations in the IRF2BPL gene can affect the brain and nervous system. The function of IRF2BPL is not yet known. Experts believe IRF2BPL is important for developing and maintaining healthy brain cells.  

Symptoms usually begin in early childhood and can get worse over time. This disorder is a lifelong condition.

SYMPTOMS

Common Symptoms

Developmental Regression: Loss of previously acquired skills (walking, talking).

Motor Issues: Ataxia (balance issues), dystonia (involuntary movements/twisting), spasticity, tremors, poor coordination.

Seizures: Various types, including infantile spasms, focal seizures.

Cognitive/Behavioral: Intellectual disability, autism spectrum disorder, anxiety, depression.

Feeding/GI: Difficulty swallowing (dysphagia), gastrointestinal dysmotility.

Brain Imaging: Cerebellar atrophy, corpus callosum abnormalities. 

Spectrum of Severity

Severe (NEDAMSS): Early onset, severe regression, profound disability, loss of walking/speech.

Milder/Late-Onset: Can present in adulthood with progressive imbalance, chorea, cognitive decline, less regression, or preserved ambulation. 

Onset & Progression

Onset is highly variable (infancy to adulthood).

Often progressive, with skill loss worsening over time, though some milder cases don't regress. 

Causes

Gene Mutation: A change (mutation) in the IRF2BPL gene (Interferon Regulatory Factor 2 Binding Protein Like).

De Novo: Most cases arise from a new mutation in the child, not inherited from parents.

Autosomal Dominant: Can be passed down, with a 50% chance of inheritance from an affected parent.

Types of Mutations: Nonsense, missense, and frameshift mutations have been identified, often truncating the protein. 

Complications

Neurological Regression: Many children experience a period of normal development followed by loss of motor skills (sitting, walking) and speech.

Epilepsy: Seizures are very common, including infantile spasms, myoclonic, absence, and tonic-clonic types, notes National Institutes of Health (NIH) | (.gov).

Movement Disorders: Ataxia (uncoordinated movement), dystonia (involuntary muscle contractions), tremor, and parkinsonism are frequent.

Feeding & Swallowing: Severe dysphagia (trouble swallowing) often necessitates feeding tubes, according to Orphanet and Child Neurology Foundation.

Brain Abnormalities: MRI scans show cerebellar atrophy, cortical/subcortical atrophy, and corpus callosum issues.

Psychiatric/Behavioral: Autism spectrum disorder (ASD), anxiety, and other behavioral issues are reported. 

Risk Factors

Genetic Mutation: The primary risk factor is the presence of a pathogenic IRF2BPL gene variant, which causes the protein to not function properly in the brain and nervous system.

Inheritance Pattern: The disorder is autosomal dominant, meaning a child of an affected individual has a 50% chance of inheriting the pathogenic variant.

Type and Location of Variant: The specific type and location of the mutation may influence the severity and age of onset of symptoms. Truncating (loss-of-function) variants often lead to the severe childhood-onset form, while some missense variants or N-terminal mutations might result in a milder, later-onset phenotype. 

Diagnosis

Clinical Presentation: Early normal development followed by loss of skills (motor, speech).

Neurological Symptoms: Seizures (epileptic encephalopathy), ataxia, dystonia, spasticity, autism, anxiety, and feeding issues.

Brain Imaging (MRI): Cortical/cerebellar atrophy, corpus callosum abnormalities.

Genetic Testing: Confirms diagnosis by identifying a pathogenic IRF2BPL mutation. 

Treatments

Therapies: Physical, Occupational, Speech, and Developmental therapies.

Medications: For seizures (e.g., sodium valproate, levetiracetam) and movement issues (e.g., baclofen for spasticity).

Nutritional Support: Feeding therapy or tubes (gastrostomy) for poor weight gain.

Specialist Care: Neurologists, orthopedists, ophthalmologists for specific issues like vision or bone health. 

 Therapy: A significant breakthrough occurred with the first child receiving an IRF2BPL gene replacement therapy in April 2025, showing promise for treating the underlying cause.

Drug Repurposing: Researchers are exploring existing drugs, like copper ATSM (CuATSM), which rescued neuronal function in lab studies and flies.

Gene Editing: Base editing and prime editing (CRISPR-based tools) are being developed as potential cures by correcting the genetic mutation.

Antisense Oligonucleotides (ASOs): These are also being investigated to target the mutated IRF2BPL mRNA. 

Type of Doctor Department : A clinical geneticist and a neurologist


Comments

Post a Comment

Popular posts from this blog

Charge Syndrome

Overview CHARGE syndrome is a recognizable genetic syndrome with known pattern of features. It is an extremely complex syndrome, involving extensive medical and physical difficulties that differ from child to child. CHARGE syndrome is correlated with genetic mutation to CHD7 and the prevalence of CHARGE syndrome is 1:10,000-1:15,000 live births. Babies with CHARGE syndrome are often born with life-threatening birth defects. They spend many months in the hospital and undergo many surgeries and other treatments. Swallowing and breathing problems make life difficult even when they come home. Most have hearing two little girls sitting on a carpet, one girl has a trach and is biting her finger.loss, vision loss, and balance problems that delay their development and communication. Despite these seemingly insurmountable obstacles, children with CHARGE syndrome often far surpass their medical, physical, educational, and social expectations. One of the hidden features of CHARGE syndrome is the ...
7 comments
Read more

Dehydration Due to Diarrheal Diseases

Overview Dehydration occurs when you use or lose more fluid than you take in, and your body doesn't have enough water and other fluids to carry out its normal functions. If you don't replace lost fluids, you will get dehydrated. Anyone may become dehydrated, but the condition is especially dangerous for young children and older adults. The most common cause of dehydration in young children is severe diarrhea and vomiting. Older adults naturally have a lower volume of water in their bodies, and may have conditions or take medications that increase the risk of dehydration. This means that even minor illnesses, such as infections affecting the lungs or bladder, can result in dehydration in older adults. Dehydration also can occur in any age group if you don't drink enough water during hot weather — especially if you are exercising vigorously. You can usually reverse mild to moderate dehydration by drinking more fluids, but severe dehydration needs immediate medical treatment. ...
Post a Comment
Read more

Ataxia with Vitamin E Deficiency

Synonyms of Ataxia with Vitamin E Deficiency AVED Familial Isolated Vitamin E Deficiency Isolated Vitamin E Deficiency General Discussion Ataxia with vitamin E deficiency (AVED) is a rare inherited neurodegenerative disorder characterized by impaired ability to coordinate voluntary movements (ataxia) and disease of the peripheral nervous system (peripheral neuropathy). AVED is a progressive disorder that can affect many different systems of the body (multisystem disorder). Specific symptoms vary from case to case. In addition to neurological symptoms, affected individuals may experience eye abnormalities, disorders affecting the heart muscles (cardiomyopathy), and abnormal curvature of the spine (scoliosis). AVED is extremely similar to a more common disorder known as Friedreich’s ataxia. AVED is inherited as an autosomal recessive trait. Vitamin E deficiency often occurs secondary to disorders that impair the absorption of vitamin E from fat including liver disorders, disorders of fat...
Post a Comment
Read more