Neurological & Genetic Disorders

The term “neurogenetic disorders” refers to conditions that involve both neurological and genetic components. These disorders affect the development and functioning of the nervous system, and they have a genetic basis. This means that defects or abnormalities in one or more genes contribute to the development of these disorders ^{[1] [2]}.

What are neurogenetic disorders?

Hereditary neurological disorders develop because of the central role that genetics play in neurological functioning. At a minimum, one-third of the genes in the body are active in the brain. These genes determine how the brain develops and functions, and in consequence, they also determine how we think and behave. Since genes play such a central role in brain development, they also contribute to diseases. Some genetic brain disorders like Huntington’s disease are the result of a mutation in a single gene ^[3]. 

Types of Neurogenetic Disorders 

There are various different categories or types of neurogenetic disorders, which are described below in more detail. 

Neurodevelopmental Disorders 

Among the neurogenetic disorders, neurodevelopmental disorders are a group of conditions that begin during the developmental period, or early in childhood. These developmental disorders result in impairments in daily functioning. Disorders in this category include attention-deficit hyperactivity disorder (ADHD), communication disorders, learning disabilities, tic disorders, autism spectrum disorder, and intellectual disabilities. The disorders in this category are considered genetic brain disorders because they are linked to gene mutations and altered gene functioning ^[4].

Neurodegenerative Diseases 

A neurodegenerative disease is a condition diagnosed when cells in the brain and peripheral nervous system stop functioning and then eventually die. These diseases are progressive and cannot be cured. Some examples of neurodegenerative diseases include Alzheimer’s disease and Parkinson’s disease ^[5].

Metabolic Disorders

Neurometabolic disorders develop because of genetic alterations that result in abnormalities with cellular metabolism. Such conditions result in problems like epilepsy and abnormal movements. Oftentimes, neurometabolic disorders develop due to enzyme dysfunction or deficiency ^[6].

Common Neurogenetic Conditions

There are numerous different neurogenetic conditions, but some are rather common and important to understand. Some of the most well-known neurogenetic disorders are detailed below. 

Huntington’s Disease

Huntington’s disease is a neurodegenerative disorder caused by a mutation of a single gene called the huntingtin gene, which is found on chromosome 4. The gene mutation causes dysfunction and eventually death in nerve cells. As a result, individuals with Huntington’s disease experience motor, cognitive, and psychiatric disturbances ^[7].

Symptoms include issues with balance and walking, difficulties with executive functioning, challenges with emotion recognition, and psychiatric symptoms including psychosis, apathy, depression, anxiety, irritability, and obsessive-compulsive behavior. Huntington’s disease results in significant impairment, and many individuals cannot continue working. In the late stages of the disease, a person will require around-the-clock care ^[7].

Fragile X Syndrome

Fragile X syndrome is a neurogenetic condition caused by a single gene mutation. Symptoms tend to be more severe in males compared to females. Individuals with fragile X syndrome experience learning and cognitive difficulties. Most males with the condition tend to have mild to moderate intellectual disability, whereas just one-third of females with the condition experience intellectual impairment ^[8]. 

In most cases, children with fragile X syndrome will show delays in speech and language development by the time they reach 2 years of age. Aside from impairments in speech and intellectual functioning, children with fragile X syndrome experience symptoms including anxiety, impulsivity, and hyperactivity. They may show features of autism spectrum disorder, and some children with the condition will have seizures ^[8]. 

Muscular Dystrophy 

Muscular dystrophy is an umbrella term referring to over 30 conditions that cause muscle weakness and degeneration in the skeletal muscles. Muscular dystrophies are genetic conditions, and they are progressive in nature, meaning they get worse over time ^[9].

As the muscles weaken, many people with muscular dystrophy are no longer able to walk. There are various different gene defects that can result in muscular dystrophy. For instance, some defects involve proteins that protect the muscles from damage. Other types of muscular dystrophy involve problems with the connective tissue or expression of toxic gene material within the muscle fibers ^[9]. 

Epilepsy

Some forms of epilepsy are considered neurogenetic disorders. For example, idiopathic epilepsy is associated with mutations in several different genes. While more research is needed, current studies suggest that epilepsy is up to 70% heritable ^[10].

Individuals who have epilepsy experience recurrent seizures. These are episodes of involuntary shaking, and they occur when a group of brain cells undergo excessive electrical discharge ^[10]. 

Tourette Syndrome

Tourette syndrome is a neurological disorder that causes involuntary movements and vocalizations called tics. When a person has tics, they cannot prevent their body from making a particular sound or movement. For example, they may repeatedly blink, grunt, or repeat a certain phrase ^[11].

Mutations in several different genes are linked to Tourette syndrome. These mutations occur in genes that play a role in neuronal connections. Some genes may have a significant effect on the development of Tourette syndrome, but it’s also possible that a combination of numerous genes with smaller effects can contribute to the condition ^[11]. 

Dementia

The term dementia refers to a variety of conditions that result in loss of cognitive functioning. This can involve difficulties with thinking, memory, and logical reasoning. There are several different types and causes of dementia. In general, dementia develops when changes in the brain cause problems with nerve cells and their connections, so they no longer work properly ^[12].

In some cases, rare gene variants can cause dementia, but the exact cause can vary based on the specific type of dementia. For instance, Alzheimer’s disease, which is the most common type of dementia, develops when abnormal proteins build up in the brain. On the other hand, vascular dementia is the result of damaged blood vessels or lack of blood and oxygen flow to the brain ^[12]. 

Genetic Causes of Neurological Disorders

There are several different genetic causes of neurological disorders. Sometimes, these conditions develop from a mutation or problem with a single gene, as is the case with Huntington’s disease or fragile X syndrome ^[7][8]. In other cases, such as with Alzheimer’s disease, several gene variants can increase the risk of a neurological disorder ^[13]. 

Sometimes, neurological disorders have multifactorial causes, meaning a variety of different genes combine to increase the risk of these disorders. In many cases, genetic risks can interact with environmental factors to cause a genetic disorder to develop ^[13]. 

Diagnosis of Neurogenetic Disorders

The specific diagnostic procedure for identifying a neurogenetic disorder will depend upon the disorder in question. Diagnosis generally begins with an assessment of neurological symptoms. A general physician can be a suitable starting point for diagnosis, but a person may need to be referred to a specialist for diagnosis and treatment.

While the specific diagnostic procedure can vary, there are some general diagnostic tools used when assessing neurogenetic disorders. For example, molecular genetic testing can assist with the diagnosis of conditions like fragile X syndrome ^[8]. 

In other cases, such as when Huntington’s disease is expected, there are numerous diagnostic tools used. A specialist diagnosing Huntington’s will conduct a clinical assessment and gather information about the patient’s family and medical history. Rating scales can be used to assess the degree of motor impairment, and a diagnosis can be confirmed based on family history of Huntington’s or a positive genetic test ^[7].

In addition to the above, diagnostic imaging tools like MRI may be used to scan the brain or examine muscles or other tissues ^[9][12]. Finally, tools like blood tests, biopsies, and amniocentesis (during pregnancy) can be used to detect abnormalities and confirm a diagnosis ^[9].

Treatment of Neurogenetic Disorders 

Treatment of neurogenetic disorders typically involves a multidisciplinary approach ^[7], and exact procedures can vary based on the type of disorder. In many cases, treatment involves symptom management, so that patients and their families can live with the disorder while maintaining the highest degree of functioning possible. Patients may take medication to reduce symptom severity or slow disease progression, which can help with management. Therapy can be helpful for patients and families, as it can help with learning coping skills and strategies for symptom management ^[7].

In addition to symptom management, gene therapies show promise for treating neurodegenerative disorders. Gene therapies may have the potential to treat Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease. While some studies have not shown any benefit, research is ongoing, and scientists are improving the effectiveness of treatments ^[14]. 

Other emerging treatments include methods like enzyme replacement therapy, amino acid supplementations, and lysine reduction therapy ^[15]. 

Living with Neurogenetic Disorders

Living with a neurogenetic disorder can be challenging for both the patient and their family. Fortunately, there are resources available. It can be helpful to work with a therapist to learn healthy coping strategies and obtain information about symptom management ^[7]. A professional like a social worker can also refer family members to resources, such as financial assistance and respite care, which can be beneficial.

Neurogenetic disorders can reduce quality of life, especially if they make it difficult to be mobile or maintain employment ^[7][9]. In this case, physical and occupational therapy and resources like wheelchairs or braces can lead to improvements ^[9]. Supportive services such as job accommodations may be needed ^[7]. In the case of conditions like fragile X syndrome, children may benefit from special education services to help them be successful at school in the face of learning and intellectual disabilities ^[8].

With treatment and support, it is possible to live with a neurogenetic disorder. Fortunately, treatments are improving, and scientists are dedicated to identifying novel treatment approaches that can improve quality of life ^[14][15].