The Impact of Genetic Testing For Rare Diseases

Diagnosing a rare disease can be a complex endeavor. The journey can be long and challenging, commonly lasting for years. Children and adults who are suspected to have a rare and undiagnosed disease often see a wide variety of doctors and specialists in search of an answer for what’s causing their symptoms.

On average, it takes roughly four to five years to reach an accurate diagnosis of rare diseases. Additionally, rare disease patients receive an average of three misdiagnoses, which can also prolong the road to relief.

That’s where genetic testing for rare diseases becomes invaluable. Depending on the type of genetic test, this process can scan nearly all of your or your loved one’s genes for important changes that may be linked to a genetic condition, which could lead to an early diagnosis.

Here, we cover who may be a candidate for rare diseases genetic testing, the various types of genetic tests, and how whole genome genetic testing, among other genetic tests, can benefit rare disease patients and their families on the journey to better health.

What is considered a rare disease?

A rare disease is defined as a disease or condition that impacts less than 200,000 people in the U.S., according to the FDA. While the National Cancer Institute (NCI) estimates that there are around 7,000 rare diseases, recent research suggests that there are actually more than 10,000 rare diseases. The number varies slightly because there’s no one consensus on what constitutes a rare disease.

The cause of many rare diseases is unknown, but they are often linked to changes in a person’s genes. It’s estimated that more than 80% of rare diseases have a genetic origin.

Examples of rare diseases that can be detected through genetic testing include:

• Cystic fibrosis
• Fragile X syndrome
• Spinal muscular atrophy
• Blood diseases such as sickle cell disease
• Alport syndrome
• Hemophilia
• Duchenne Muscular Dystrophy (DMD)
• Tay-Sachs disease
• Charcot-Marie-tooth disease
• Ehlers-Danlos syndrome (EDS)
• Huntington’s disease
• Dravet syndrome

Almost 10% of American populations are affected by a rare disease and about half of them are children.

What is genetic testing?

Genetic testing is a type of lab test that scans your genes and DNA for changes (also called genetic variants). Genetic tests can identify specific genes that contain abnormalities and can tell you whether these changes are associated with a genetic disease.

Genetic testing is a straightforward process and is minimally invasive – all that’s required is a blood, saliva, or buccal sample.

Who needs genetic testing for rare diseases?

Genetically linked rare diseases can be inherited or develop later in life. People who are commonly referred for rare disease genetic testing include:

• Individuals who have symptoms that are characteristic of a rare disease or multiple rare diseases
• Those who have multiple family members affected by similar symptoms
• Newborns who have early onset symptoms, such as seizures, or congenital anomalies (also known as congenital disorders)
• People who are planning on having children, where one or both parents are known to be carriers of a genetic variant that is linked to a genetic disease
• People who are married to a blood relative

Types of genetic testing for rare disorders

There are multiple types of genetic testing that can help detect rare and undiagnosed diseases. Each test serves a unique purpose and analyzes a different amount of genes. Here are four common test types.

Single gene sequencing

As the name suggests, single gene sequencing looks for changes in one specific gene. This targeted test can be helpful when you’re trying to determine whether you have a potentially disease-causing genetic change (or pathogenic variant) associated with a rare condition that runs in your family.

Gene panel sequencing

Genetic panel tests look at one panel (or group) of genes for changes that could indicate disease. These specific genes are grouped together based on symptoms or the type of diseases you’re looking for. Examples of gene panel tests include “epilepsy panel”, “inherited renal disease” and “intellectual disability.”

Although panel testing can analyze anywhere from two genes to more than 1,000, standard targeted panel sequencing tests typically only cover less than 0.1% of the human genome, making them somewhat limited in their findings.

Whole exome sequencing (WES)

Whole exome sequencing looks at all the genes inside your exome, which are known as protein-coding regions. The genes in these regions create proteins, which are responsible for almost every cell function in your body.

While whole exome sequencing analyzes a greater portion of your genome than panel testing, it still only covers about 1-2% of your entire genome.

Whole genome sequencing (WGS)

Whole genome sequencing is a more extensive genetic test. It analyzes more than 99% of your genome, which gives it broad coverage in the search for variants.

Whole genome sequencing technologies accurately detect a causative gene and single nucleotide variants. These tests can also accurately identify complicated gene changes like structural variants and copy number variants across protein-coding and non-coding regions.

Genomic sequencing is helpful for making a molecular diagnosis of rare diseases when the cause hasn’t yet been narrowed down. It provides you with the most sequencing data of any genetic test, giving you and your provider more insights.

Benefits of genetic testing

Genetic testing is a valuable tool for patients and healthcare providers alike. The more information you have about your genes, the more likely you and your provider are to be able to make informed decisions about possible treatment options.

A few benefits of genetic testing for rare diseases include:

• Diagnostic yield: Certain genetic tests, like a whole genome test, can achieve up to a 50% positive genetic diagnosis rate, which can help speed the process to receiving an accurate diagnosis. This means you or your loved one could receive important health information faster, helping to make informed decisions about treatment sooner.
• More health information: Regardless of whether a diagnosis is found, genetic testing can still provide answers related to symptoms you or your child are experiencing. It can also help rule out a number of suspected genetic diseases and inform next steps in your diagnostic odyssey.
• Personalized treatment: Genetic testing can uncover unique biomarkers that can help predict which treatments may be most or less effective for your personal situation (which is called precision medicine).
• Family planning: If you have a rare genetic disease and are interested in having a family, genetic testing can provide information into genetic diseases so you can appropriately plan for your future. This can help you understand the risk of you or your partner passing on a genetic variant that could result in a rare disease in your child.

Does genetic testing always end in a rare disease diagnosis?

Because not all rare diseases are genetic in nature, not every test will return a diagnosis. It is possible that you could have symptoms that are characteristic of a rare disease but may not receive a confirmative rare disease diagnosis. It’s important to know this in advance to set realistic expectations for your results.

While some tests may not return results that have clinical utility, they still offer a way to rule certain genetic diseases out of the equation. This can still help bring you closer to an accurate diagnosis. Genetic testing also gives your peace of mind, ensuring you’re not leaving any options on the table when it comes to learning more about your health.

The value of genetic counseling for rare diseases

Some genetic test providers, like Inocras, offer access to genetic counselors who are available to discuss the results of your test. Genetic counselors are experts that help people understand how their genetic makeup can impact their health and life.

These counselors can also help you with the following:

• Adapting to and coping with the medical, psychological, and familial implications of genetic and inherited diseases
• Supporting you and your family in making informed decisions about your health and disease management
• Offering specialty information about medical genetics and the clinical findings of your test to your health care provider
• Educating you and your family about human genetics and how they play a role in your family history
• Making recommendations for next steps in your health journey

Is genetic testing covered by insurance?

Whether genetic testing for rare diseases is covered by your insurance will depend on the following factors:

• Your location
• Your specific health plan and insurance provider
• The type and provider of your test
• Your medical and family history
• Whether genetic testing was recommended by your doctor
• Whether you’ve obtained prior authorization

The answer to this question is case-dependent, which is why it’s always a good idea to call your insurance company directly for answers.

How can I get genetic testing for a rare disease?

Genetic testing for rare diseases can be done with or without a doctor referral. The Inocras RareVision test is a whole genome sequencing test designed for those who:

• Want answers about their symptoms
• Want a clear, accurate rare disease diagnosis
• Have concerns about hereditary rare diseases and/or are planning a family with potential rare disease risks in mind

This clinical whole genome test utilizes an up-to-date online database to identify genes associated with rare diseases. It only takes two weeks (on average) and requires an at-home blood draw by a phlebotomist.

There are two ways to order the test:

1. You can request an order via Inocras’s online portal for approval from a telehealth provider
2. You can ask your provider to place an order for you

Your report will come with actionable suggestions to help you take control of your health. RareVision also comes with access to a genetic counselor who can help explain your results and findings at no extra cost.

Take one step closer to clarity: order a rare disease genetic test

Genetic testing can be a great option if you are struggling to diagnose and manage symptoms that are affecting your daily life. Whole genome genetic testing in particular can be particularly helpful because it provides more comprehensive and detailed genetic information than other types of genetic testing.

Take back control of your health. Order your RareVision test.