Understanding the Genetics of Guillain-Barré Syndrome

Disclaimer: This article is for informational purposes only and is not intended to diagnose any conditions. LifeDNA does not provide diagnostic services for any conditions mentioned in this or any other article.

One day you feel perfectly fine, then on the next, your muscles feel weak, and simple movements become a struggle. This sudden loss of control is what makes Guillain-Barré syndrome so alarming. Though anyone may develop it, adults over 50 are most at risk. Despite its unpredictable and even sudden nature, Guillain-Barré syndrome, or GBS, is not contagious and its exact cause remains unknown, although recent research suggests that genetics may play a role in this luckily rather rare syndrome. Understanding the known symptoms and pathological attributes of GBS is important because early recognition and medical care can make a big difference in recovery and overall wellness .

What is Guillain-Barré Syndrome?

Guillain-Barré syndrome is a rare condition where the body’s immune system mistakenly attacks the nerves outside the brain and spinal cord. These nerves help control movement and sensations like touch, pain, and temperature. Guillain-Barré syndrome or GBS may affect anyone, but certain factors may increase the likelihood of developing this condition.

What Causes Guillain-Barré Syndrome?

The exact cause of Guillain-Barré syndrome (GBS) is still unknown, but researchers believe it is triggered by an immune system malfunction. In a healthy body, the immune system defends against harmful bacteria and viruses. However, in GBS, the immune system mistakenly attacks the peripheral nerves, the network responsible for movement and sensation leading to weakness, tingling, and even paralysis.

In most cases, GBS starts after an infection. The most common trigger is a bacteria called Campylobacter jejuni, which can be found in undercooked food and causes food poisoning. Other infections, like the flu, pneumonia, or viruses such as Zika and that of COVID-19, have also been linked to increase the risk of developing GBS. Scientists believe that when the body fights off these infections, the immune system may get confused. Some bacteria and viruses have proteins that may appear to be similar to parts of our nerve cells. Because of this similarity, the immune system mistakenly attacks the nerves instead of just fighting off the infection.

Although infections are the most common trigger, GBS has also been reported after surgeries or, in very rare cases, after vaccinations. However, the risk of getting GBS from a vaccine is extremely low. Some researchers believe that certain people may have a genetic trait that is associated with immunological function that makes them more likely to develop GBS, but this is still being studied.

Not everyone who gets an infection or undergoes surgery develops GBS, which is why scientists continue to research why it happens in some people and not others. The more we understand about its causes, the better doctors can work on ways to prevent, diagnose, and treat GBS early.

Genetics of Guillain-Barré Syndrome

Scientists suggest that both environmental and genetic predisposition could heighten the susceptibility to the pathophysiological characteristics of GBS. A 2021 study has identified several genes that are linked to the increase of the risk of developing GBS. These include HLA, CD1A, FAS, FcGR, ICAM1, interleukin genes, NOD, TLR4, and TNF-α. These genes play important roles in regulating the immune system, controlling inflammation, and maintaining nerve health. Although the specific roles of these genes concerning GBS is still debated, their dysfunction may contribute to nerve damage by triggering inflammation, disrupting immune responses, or interfering with nerve repair. Understanding these genetic factors may help researchers develop better treatments and possible ways to prevent GBS.

To further investigate these genetic links, researchers conducted a large-scale review of studies examining the connection between genetic variations and GBS risk. Out of 333 research papers, they selected 41 studies that analyzed 220 genetic variations. Among these, 59 variations had enough supported data that show significant association with GBS. The results highlighted four specific genetic variations—FcγR IIA rs1801274, TNF-α rs1800629, HLA DRB1*0401, and HLA DRB1*1301 were significantly associated with an increased risk of GBS.The study also found that certain genetic variations were more common in specific populations. In Asian populations, TNF-α rs1800629, TNF-α rs1800630, and TLR4 rs4986790 were linked to a higher risk of GBS. In Caucasian populations, the variations FcγR IIA rs1801274 and HLA DRB1*14 were associated with increased risk. Additionally, TNF-α rs1800629 was specifically linked to the AMAN subtype of GBS (see below for the subtypes).Among genetic variations that were studied less frequently, 17 additional variations were identified as potentially linked to GBS risk. Most findings were confirmed to be reliable, although the FcγR IIA rs1801274 showed some inconsistencies in the meta-analysis.

By identifying the genetic factors involved in GBS, researchers hope to improve treatments and possibly develop new ways of symptom management and complications prevention. Currently, GBS is treated by controlling the immune attack, but a better understanding of the genetic pathways could lead to more targeted therapies in the future.

Symptoms of Guillain-Barré Syndrome

GBS affects the nervous system in several ways, leading to various symptoms. These progress over time and can become life-threatening if they affect the muscles involved in breathing and other vital functions. Below are the key symptoms:

Muscle Weakness: The immune system mistakenly damages nerves that help muscles move. This typically begins in the feet and legs and then may progress to the arms, face, and even the muscles needed for breathing.
Numbness or Sensation Changes: Nerve damage can cause tingling, numbness, or unexplained pain, typically starting in the hands and feet. Some people experience a crawling sensation under the skin, known as formication.
Blood Clots: If Guillain-Barré syndrome makes it hard to move, blood clots can become a concern. To help with blood flow, doctors might suggest blood thinners and special stockings until you’re able to walk again.
Pain: Deep muscle pain, especially in the back and legs, is common and may worsen at night.
Coordination and Balance Issues: Weakness and nerve damage can make walking difficult and cause unsteadiness.
Facial and Eye Muscle Dysfunction: Guillain-Barré syndrome may weaken the nerves in the face and eyes, making it difficult to speak, chew, swallow, or move the eyes properly.
Autonomic Nervous System Disruptions: This may also affect automatic body functions like heart rate, blood pressure, digestion, and bladder control, leading to unexpected changes.

Types of Guillain-Barré Syndrome

There are several subtypes of GBS, each affecting different parts of the nervous system:

Acute Inflammatory Demyelinating Polyradiculoneuropathy (AIDP): The most common form, AIDP occurs when the immune system attacks the protective myelin sheath surrounding the body of a neuron or a nerve cell. Myelin helps electrical signals travel efficiently along nerves, so when it is damaged, signal transmission slows down, leading to muscle weakness and sensory changes.
Acute Motor Axonal Neuropathy (AMAN) and Acute Motor-Sensory Axonal Neuropathy (AMSAN): These forms involve direct damage to the axons—the core fibers within nerves responsible for transmitting signals. AMAN primarily affects motor nerves, causing muscle weakness and paralysis, while AMSAN impacts both motor and sensory nerves, leading to more severe symptoms and a longer recovery period.
Miller Fisher Syndrome (MFS): A rare subtype of GBS that primarily affects the cranial nerves, leading to problems with eye movement, loss of coordination, and reduced reflexes. Unlike other forms, this often starts with double vision or difficulty controlling eye muscles before progressing to balance and movement issues.

How is Guillain-Barré Syndrome Diagnosed?

Because GBS shares symptoms with other neurological disorders, doctors use several tests to confirm a diagnosis:

Medical History and Physical Exam: Doctors check for muscle weakness, reflex changes, and symmetrical symptoms (meaning if symptoms affect both sides of the body).
Nerve Conduction Studies (NCV): These tests measure how fast electrical signals travel through the nerves, helping identify nerve damage.
Cerebrospinal Fluid (CSF) Analysis: A spinal tap checks for increased protein levels in the fluid surrounding the brain and spinal cord, which is a common sign of GBS.
Imaging Tests: MRI scans help rule out other conditions that could be causing similar symptoms.

Treatment or Management Options for Guillain-Barré Syndrome

There is no complete cure for GBS, but early treatment can speed up recovery and reduce complications. Recovering of course is different for everyone. Some people bounce back in just a few months, while for some others it may take much longer, sometimes even years. Here are some ways to manage GBS

Plasma Exchange (Plasmapheresis): This procedure removes harmful antibodies from the blood, which may help stop the immune attack on nerves.
Intravenous Immunoglobulin (IVIg) Therapy: Provides healthy antibodies to help balance the immune system and reduce nerve inflammation.
Breathing Support: In severe cases, a ventilator may be needed to assist with breathing.

Heart and Blood Pressure Monitoring: To manage irregular heartbeats or fluctuations in blood pressure.
Pain Management: Medications can help ease nerve pain and discomfort.
Physical and Occupational Therapy: Rehabilitation plays a key role in helping individuals regain movement, strength, and independence.

The Latest Research on Guillain-Barré Syndrome

Researchers are continuously studying GBS to improve treatments and understand its causes. Current research focuses on treatment such as enhancing intravenous immunoglobulin (IVIg) therapy, which helps regulate the immune system and reduce nerve damage. Studies are focused on optimizing dosage and timing to improve recovery rates and minimize side effects. Additionally, new treatments are being developed to target nerve inflammation more effectively, with the goal of speeding up recovery and reducing long-term complications. With ongoing advancements in neurology and immunology, scientists hope to not only improve treatment outcomes but also find ways to predict and prevent GBS in the future.