What Is Familial Encephalopathy With Neuroserpin Inclusion Bodies?

You may not have heard of familial encephalopathy with neuroserpin inclusion bodies, or FENIB. This is because it is a very rare genetic disease that has only been seen in a few families worldwide. Often causing dementia (affecting general memory and thinking abilities), the symptoms of FENIB can be life-changing. So, what causes this disease? And can it be treated? In this article, we explore this lesser-known condition further.

What is familial encephalopathy with neuroserpin inclusion bodies (FENIB)?

Familial encephalopathy with neuroserpin inclusion bodies (FENIB) is referred to as a familial neurodegenerative disease.¹ If we break this term down, familial means that the disease is hereditary and passed down from parents to children through a family’s generations. A neurodegenerative disease is a condition which causes damage and destruction of the nervous system, particularly the brain. 

It is also classified as an autosomal dominant disease.² This means that for the disease to be passed from parents to children, only one parent out of the two must have the gene abnormality causing the disease for the child to also get it. This makes it a 50% risk for passing on the abnormal gene.

This is the opposite of an autosomal recessive disease, which would need both parents to have the gene abnormality in order for it to be passed down to the child.  

Given the rarity of this disease, there is not a lot of research available, and therefore it is still not very well known, However, it is known that the most noticeable characterisation of FENIB is the associated  Dementia which refers to a general loss of memory and impairment of thinking caused by various syndromes. 

But, before we examine the symptoms of FENIB more closely, it’s important to understand how it is caused. 

What causes familial encephalopathy with neuroserpin inclusion bodies (FENIB)?

Familial encephalopathy with neuroserpin inclusion bodies is caused by a gene mutation – a change in your DNA. 

We all have a gene called the SERPINI1 gene, which holds the ‘coding’ (instructions) to create a protein called neuroserpin. 

However, FENIB is caused when there is a mutation in this gene’s coding, which results in mutant or unstable neuroserpin proteins. These proteins then aggregate (link together) to form ‘inclusions’ which are referred to as ‘Collins bodies’.¹  

So, ‘Collins bodies’ are essentially an accumulation of this mutant protein, neuroserpin, within the nerve cells.² Collins bodies affect how nerve cells work and can impair their normal function, which is how the symptoms of FENIB begin to come about. 

The disease is progressive, meaning it continues to worsen. As time goes on, more Collins bodies form, and therefore the central nervous system becomes more and more affected (NORD).

Symptoms of familial encephalopathy with neuroserpin inclusion bodies (FENIB)

This relationship between the formation of Collins bodies and the subsequent developing symptoms has not yet been fully explained, and the research has been limited given that there have only been a handful of families in the world who have presents with FENIB. 

However, we do know that the age at which a patient develops symptoms, the speed with which the disease progresses, and the severity of the condition can all depend on the neuroserpin gene’s specific mutation. According to NORD (The National Organization for Rare Disorders in the USA), if patients have the same mutation, they will often develop symptoms at around the same age. 

Someone can develop symptoms of FENIB before the age of 10, but it is also possible for no symptoms to appear before the age of 50 or 60. 

Myoclonus

From the limited research available, one literature review of reporting FENIB patients found one of the most common symptoms to be ‘myoclonus’ – sudden and jerky muscle movements that are involuntary.⁴

Dementia

It also found that a progressive decline in cognitive function was a very common symptom, referring to a worsening reduction in one’s cognitive abilities such as memory, judgement, and awareness of their surroundings.⁴

This cognitive decline may be referred to as dementia. Whilst caused by different syndromes, dementia is an umbrella term for problems including: 

• A reduction in thinking speed
• Loss of memory 
• Change in mood
• Impaired judgement 
• Problems with language and speech 
• Difficulty with movement 

Epileptic seizures

This review also found that some FENIB patients had suffered epileptic seizures, too.³ 

Over 50% of these patients had experienced generalised seizures, but others had also had: 

• Generalised Tonic-Clonic Seizures (GTCS): often involving a loss of consciousness followed by muscle contractions⁵
• Absence seizures: not involving movement, the patient becomes unresponsive and appears to be ‘staring’⁶
• Focal impaired awareness seizures: the patient’s awareness of their surroundings is impaired, it can involve muscle seizures but not always

Perseveration

Another finding associated with symptoms of FENIB by NORD is what is referred to as ‘perseveration’. This is when someone exhibits repetitive, uncontrollable behaviours such as repeating a gesture or a word. 

Progressive Myoclonic Epilepsy (PME)

If FENIB symptoms begin early in a patient’s life, such as between the ages of 10 and 30, more severe seizures may be symptomatic, including progressive myoclonic epilepsy (PME). This refers to a group of rare types of epilepsy that worsens with time, and is difficult to treat with medication (Epilepsy Foundation).

Unfortunately, these patients or others who develop symptoms early in life may only survive for a few years following the onset of symptoms (NORD).

Diagnosing familial encephalopathy with neuroserpin inclusion bodies (FENIB)

As with any rare disorder, FENIB would require a specialist practitioner to confirm a diagnosis, particularly one who specialises in neurological diseases (diseases of the nervous system). 

Diagnosis would usually start with a clinical evaluation, a review of the patient’s medical history, and by establishing their symptoms. A range of medical tests would then be carried out in order to determine that no other conditions were responsible for the symptoms. 

These tests may include: 

• An MRI scan of the brain
• A CT scan of the brain
• An electroencephalogram (EEG): a procedure which records brain activity
• A neuropsychological assessment: testing the brain function

Once other conditions are ruled out, the most important test to confirm a FENIB diagnosis is a genetic analysis to find the gene mutation which causes the disease.

In rarer circumstances, a brain tissue biopsy (a sample taken of the brain) may be used to confirm the presence of Collins bodies – confirming the FENIB diagnosis. 

As stated, this is a very rare genetic disorder, and is certainly not one which is being diagnosed regularly in healthcare establishments. 

Prognosis of familial encephalopathy with neuroserpin inclusion bodies (FENIB)

Unfortunately, as a progressive disease, FENIB by its very nature worsens over time. As mentioned above, if a patient develops FENIB early in life, their prognosis is likely going to be worse as their symptoms (such as seizures) will be more severe and debilitating, and could lead to death. 

In those who develop FENIB symptoms later in life, the main symptom of dementia/cognitive decline will be what affects their quality of life the most. With loss of memory, thinking skills, awareness etc., patients suffering dementia will gradually lose the ability to live independently. As the disease progresses, they will likely need to be cared for by family or in a specialist facility (NORD).

Treating familial encephalopathy with neuroserpin inclusion bodies (FENIB)

Whilst there may be clinical trials or studies that FENIB patients can participate in, unfortunately there is not a known cure for FENIB. The only way that healthcare professionals can treat it is by treating the specific symptoms patients present with to improve their quality of life. 

This could mean, for example, developing coping strategies and lifestyle changes to help someone experiencing dementia as a symptom, or trying different treatments for FENIB-associated seizures. 

Ultimately, ‘treatment’ revolves around trying to make the patient’s symptoms as manageable as possible. 

Where can I find out more? 

Suppose you want to read more about this rare disease. In that case, you can visit sites such as NORD (The National Organization for Rare Disorders in the USA), the Genetic and Rare Diseases (GARD) information centre and Orphanet.

While research is still limited, there may be future studies which could reveal more about FENIB. 

Summary 

• Familial encephalopathy with neuroserpin inclusion bodies: FENIB
• A genetic disorder which progresses over time
• So rare that it has only been seen in a few families in the world
• Caused by a gene mutation
• Symptoms can start as early as age 10, or may not present until age 50
• Symptoms can include dementia, muscle twitching and various seizures
• Prognosis can vary depending on how early the symptoms begin
• The earlier the symptoms begin, the worse the prognosis
• Many patients will eventually lose the ability to live independently
• There is no treatment for FENIB itself, but healthcare professionals will try to treat the patient’s symptoms
• The research on FENIB is limited at the moment but you can find out more at sites like NORD, GARD and Orphanet