Overview 

De Barsy Syndrome (DBS) is an exceedingly rare genetic disorder caused by genetic mutations in the genes PYCR1 or ALDH18A1. These genes help cells produce enzymes that work with the amino acid proline in the formation and maintenance of collagen and connective tissues within the body.^1,2 Collagen is used to help joints and tendons function, while connective tissue supports, separates, and connects bodily organs and other tissues. Some of the signs and symptoms people with this condition may have include:^1,3 

• Cutis laxa
• Progeroid or prematurely ageing features
• Delayed physical and developmental growth
• Brain and nerve abnormalities
• Movement problems

DBS is a rare disease; hence, the information about its development, diagnosis, and treatment is limited, as well as the understanding of the relationship between DBS and seizure disorders.^1,3

Seizure disorders in DBS

The nervous system runs through the entire body. It connects the brain and spinal cord (central nervous system) to the body, from tissues to organs, to whole systems via nerve cells in the peripheral nervous system. This makes seizure disorders in DBS a significant concern, as they can have a big impact on how we use our bodies.^4,5

Normally, nerve cells send signals to one another in some regulated form or pattern that aids in the normal functioning of the brain and body. However, seizures occur when this pattern is disrupted and nerve cells in the brain send unregulated, abnormal electrical signals. The misfiring of these nerve cells in the brain leads to malfunctioning not just in the brain itself, but also in other regions of the body, related to the area of mismanagement in the brain, which manifests as a particular type of seizure.^4,5

Epilepsy is a condition that describes multiple uncontrolled seizures. Depending on the person and the type of seizure disorder they have, each seizure may have different triggers, appearances, causes, and levels of severity.⁴

Types of seizures reported

Some examples of seizure disorders reported in people with DBS include:^4,5,6

• Generalised tonic-clonic seizures
• Seizures caused by low calcium levels
• Focal seizures

Possible triggers and causes

People diagnosed with DBS often report having brain structure anomalies. The combined impact of weak collagen and connective tissue issues has led to deviations from normal brain structure development, resulting in the onset of seizure disorders. Brain structure irregularities with the potential to trigger these seizures include:^1,2

• An underdeveloped corpus callosum
• Colpocephaly
• Ventricular dilatation, also known as ventriculomegaly

Metabolic stressors may also be a possible contributing factor to the development of seizures. The impaired collagen and connective tissue manifest in the deterioration of the myelin around nerve cells, which are critical to the normal transmission of electrical activity from one nerve cell to another.^1,2

EEG findings in DBS

Electroencephalography (EEG) is a test where electrodes with receptors are placed at strategic areas around the head. The receptors then pick up the electrical activity in different parts of the brain. A graph with various lines and waves depicts the brain activity they pick up, and each line represents the activity of a certain area or region of the brain. 

General EEG characteristics

There has been a variety of EEG patterns reported in people with seizure disorders related to DBS. The descriptions of general EEG characteristics provided in case studies and research include:^1,2,6

• Nonspecific and unremarkable
• Minimal background activity

Seizure-related patterns

Other cases provided supplementary information on specific EEG patterns and features that led to a diagnosis. The EEG reading of a five-month-old infant led to a diagnosis of partial focal seizures because the following patterns were identified:⁶

• Multifocal spikes, representing quick spells of abnormal activity in multiple locations of the brain
• Slow activity waves, representing decreased levels of alertness
• No sleep spindles, representing abnormal brain activity while asleep

The wide variation in the limited reports about EEG findings makes it challenging to classify general and case-specific EEG characteristics in people with seizure disorders in DBS. Such limitations also hinder the long-term study of how these EEG characteristics and patterns change over time.^1,2,6

Role of EEG in diagnosis and monitoring

An EEG must be completed when there is evidence of a nervous system disorder within a person. A first-time seizure and upon admission at a healthcare facility for a seizure disorder are two situations where it would be performed. Its purpose is to compare readings with those collected from future routine EEG tests and other diagnostic and monitoring procedures.^4,7 

Neuroimaging correlation

The images of the bones, organs, tissues, and blood vessels of the brain generated by magnetic resonance imaging (MRI) and computer tomography (CT) scans showcase how these diseases, disorders, and conditions manifest themselves in the human body. Utilising multiple imaging tests can help produce more detailed analyses of EEG characteristics and patterns.⁴

Treatment and support

General treatment for DBS

For cases of DBS in general, assistance in guiding physical and developmental progression, especially in cases where a diagnosis was given in infancy, is a suggested method of treating the other physical manifestations of this condition. There are also surgical rehabilitative programs currently being studied for those diagnosed with DBS to treat abnormalities in bones and joints and improve mobility and posture.³ 

Anti-seizure medications

Anti-seizure medications are prescribed to manage seizure disorders among those with DBS. The prescription of these medications and maintaining a routine of getting EEG readings periodically is the most recommended plan of action to treat seizure disorders in DBS.^4,6

Support

Counselling for people with DBS and other secondary conditions and their families and loved ones is recommended as they undergo treatment, management planning and execution. As a loved one receives their diagnosis and begins their plan of care, anyone can bottle up the many thoughts and feelings that come up, whether it be the person with the diagnosis or their family. It can be a challenging time for everyone involved since this condition is so rare.^8,9 

There is still much that is unknown about the type of care that would help treat and manage DBS. Talking to a trusted person, such as in therapy or counselling, can create a safe space to open up and voice your thoughts and feelings. Other people may feel the same way, and they can help you find ways to manage those thoughts and feelings as you care for your loved one.

Summary

• DBS is a rare disorder caused by changes in the genes that build and maintain collagen and connective tissue
• Abnormal changes in the brain and nervous system cause seizure disorders to happen in DBS
• EEG is important in diagnosing and monitoring seizure disorders, even though there is not much data and information about how EEG readings appear in DBS
• The most recommended ways of treating and managing seizure disorders in DBS are prescription antiseizure medications and routine EEG tests
• The only surefire way to get a clear DBS diagnosis is by molecular testing of the changed genes
• Adding new data and information from research and case studies can build upon our current knowledge and understanding of seizure disorders and EEG findings in DBS