Familial encephalopathy with neuroserpin inclusion bodies

Description

Familial encephalopathy with neuroserpin inclusion bodies (FENIB) is a disorder that causes progressive dysfunction of the brain (encephalopathy). This condition is characterized by a loss of intellectual functioning (dementia) and seizures.

The first signs of intellectual impairment in individuals with FENIB may be problems with attention and concentration. Affected individuals may have trouble regulating their thoughts or speech. As the condition progresses, personality changes develop, and judgment, insight, and memory become impaired. Affected individuals lose the ability to perform the activities of daily living, and most eventually require comprehensive care.

People with FENIB have seizures that involve a sudden, involuntary muscle jerking or twitching (myoclonus). Many also experience at least one other form of seizure, typically generalized seizures that involve a loss of consciousness, muscle rigidity, and convulsions. In rare cases, people with FENIB have prolonged episodes of seizure activity that last several minutes (status epilepticus). In most people with FENIB, anti-seizure medications are not effective. Many people with FENIB have other types of involuntary movement (dyskinesia).

The signs and symptoms of FENIB can appear at any age, and they vary in severity. In severe cases, dementia can appear in childhood or adolescence and is often the first sign of the condition. Less severe cases are characterized by a progressive decline in intellectual functioning that begins in mid- to late adulthood.

People with FENIB have a shortened life expectancy. The earlier the signs and symptoms appear, the greater the impact on life expectancy. Causes of death in people with FENIB include status epilepticus and pneumonia.

Frequency

FENIB appears to be very rare. The condition was first described in 1999 and at least 13 affected individuals have been reported worldwide.

Causes

FENIB is caused by variants (also called mutations) in the SERPINI1 gene. This gene provides instructions for making a protein called neuroserpin, which is found primarily in nerve cells (neurons). This protein helps neurons divide and mature so they can take on specific functions (differentiation). The connections between neurons (synapses) also need neuroserpin to function properly, which suggests that this protein may be important for learning and memory.

SERPINI1 gene variants can cause cells to produce an abnormally shaped, unstable form of neuroserpin. Within neurons, these altered neuroserpin proteins attach to one another and form chains (neuroserpin polymers) that clump together to form neuroserpin inclusion bodies. These inclusion bodies disrupt the normal functioning of neurons and ultimately lead to cell death. Additionally, the formation of neruoserpin polymers likely increases the release of calcium ions into the cell. This can lead to certain neurons becoming more active than usual, which may trigger the abnormal brain activity that is associated with seizures in people with FENIB.

The encephalopathy and dementia in people with FENIB occur as neuroserpin inclusion bodies accumulate in the brain, causing the gradual loss of neurons. Larger numbers of inclusion bodies cause more severity of the neurological problems. People with severe FENIB tend to have more widespread neuron loss than those with milder cases of FENIB.

Inheritance

FENIB is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In some cases, this condition is familial, which means an affected person inherits the variant from one affected parent. Other cases are sporadic and result from a new (de novo) variant in the gene that occurs during the formation of reproductive cells (eggs or sperm) in an affected individual's parent or during early embryonic development. These affected individuals typically have no history of the disorder in their family.

Autosomal dominant inheritance. Credit: U.S. National Library of Medicine.

Autosomal dominant inheritance with a new (de novo) mutation. Credit: U.S. National Library of Medicine.

Other Names for This Condition

• Familial dementia with neuroserpin inclusion bodies
• FENIB
• Neuroserpin encephalopathy
• neuroserpinosis
• Progressive myoclonus epilepsy associated with neuroserpin inclusion bodies
• Progressive myoclonus epilepsy associated with neuroserpinosis

Where this page came from

This page was imported from MedlinePlus Genetics, National Library of Medicine. Courtesy of MedlinePlus from the National Library of Medicine; its genetics summaries and the illustrations credited to the library are in the public domain. Pictures credited to others are not copied.

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