Genetic Testing for Rare Diseases with Sequencing.com

In this article, we discuss what is a rare disease, cover some examples of rare diseases, and look at how Sequencing.com’s Rare Disease Screen DNA analysis app can help you test more than 1,200 rare diseases, syndromes, conditions, and traits.

What is a Rare Disease?

A rare disease refers to a disorder, condition, or disease that affects a small percentage of the population at any given time.

For example, in the United States, a rare disease is defined as a disease that affects less than 200,000 individuals, while in the European Union, it affects fewer than 1 in 2,000 individuals. 

Rare diseases might also be called orphan diseases according to the US Orphan Drug Act of 1983. This act was created to support incentive programs to develop new drugs and treatment options for rare diseases.

Rare diseases can be heritable or nonheritable. The majority are thought to be heritable, which means directly caused by abnormalities in genes or chromosomes.

Rare diseases are usually progressive and some are very disabling. Making a diagnosis for a rare disease can often be challenging, and healthcare professionals typically request genetic tests in order to confirm the diagnosis. Early diagnosis results in prompt care treatment that may reduce the likelihood of long-term disability complications.

How many Rare Diseases exist?

There are thousands of known rare diseases and hundreds more are discovered every year. Because the majority of rare diseases are caused by changes in a person’s DNA, genetic testing, such as exome sequencing and whole genom sequencing, have become one of the most important and powerful tests for detecting a rare disease.

If you think you or a loved one has a rare disease, genetic counseling can help determine which DNA test is best. It can also help you understand a genetic report as well as the results from DNA apps.

If you’ve already taken a DNA test, such as from 23andMe, Ancestry, GeneDx, or Ambry Genetics, DNA-powered apps that focus on rare disease detection can now be used. These apps analyze the raw DNA data from a wide-range of genetic tests and genome sequencing. Apps are discussed further near the end of this article.

So what are some examples of rare genetic diseases?

Naxos Disease

Naxos disease is an inherited condition associated with an abnormal heartbeat called arrhythmogenic right ventricular dysplasia (ARVD), peculiar woolly hair and skin involvement called palmoplantar keratoderma. Carvajal syndrome is a variant of Naxos disease. 

People living with Naxos disease are at high risk of sudden cardiac death due to a deadly heart arrhythmia called ventricular tachycardia. Therefore, implantation of an automatic cardioverter defibrillator is indicated for the prevention of sudden death in these patients.

Naxos disease shows us that as long as a rare disease is accurately detected, the harmful impact of the disease may be able to be minimized or avoided by implementing preventive measures.

Rippling Muscle Disease

Rippling muscle disease is a benign condition that primarily affects the muscles. It is characterized by increased muscle irritability resulting in visible ripples which spread across skeletal muscles and are provoked by stretch, percussion or movement. The muscles closest to the body’s center (proximal muscles) are most frequently affected. 

Signs and symptoms generally begin during late childhood or adolescence. Management is based on specific symptoms and severity.

Caffey Disease

Caffey disease is a benign disorder that most often occurs in infants. It is also known as infantile cortical hyperostosis.

Caffey disease is characterized by inflammation with excessive formation of new bone (hyperostosis), which results in bone abnormalities in the jawbone, shoulder blades, collarbones (clavicles), and the shafts of long bones in the libs. Babies may present with fever, irritability pain and soft tissue swelling. Symptoms may resolve spontaneously.

Human Fish-Eye Disease

Fish-eye disease is a rare disease that affects the front surface of the eyes (the corneas) causing corneal clouding. It is also called partial LCAT deficiency.

Diffuse corneal opacities can lead to severely impaired vision. Management of the disease depends on the signs and symptoms present in each person. In severe cases, corneal transplantation may be performed.

Muscle Eye Brain Disease

Muscle eye brain disease is a genetic, degenerative muscular disorder. It is a hereditary disease associated with developmental delay and intellectual disability.

Signs and symptoms will vary from person to person, but very frequently present symptoms that may include muscle weakness (hypotonia), glaucoma, and brain abnormalities.

Muscle eye brain disease is a lifelong progressive disorder caused by alterations in the POMGNT1 gene. There is no cure for this disease, and the treatment is usually given to control signs and symptoms and improve quality of life.

Thin Basement Membrane Disease

This hereditary kidney disease affects the glomeruli, which is a collection of very small blood vessels in the kidneys. Some patients may present with small amounts of blood in the urine without any other symptoms.

While some people with this disease may be healthy throughout most of their life, other people can have more severe kidney disease.

How Can I Test for Rare Diseases?

If you fear that a loved one may have, or may inherit, a rare disease, DNA testing and analysis may help. For example, a DNA test can indicate that you ‘carry’ a rare disease. This means you aren’t affected by the disease but your children may be.

Using the Rare Disease Screen app on Sequencing.com, you can analyze your DNA for more than 1,200 rare diseases, syndromes, conditions, and traits.

The ability of this powerful DNA app to analyze each trait, condition, and disease will depend upon the amount of genetic data in your genetic data file. If there is not enough genetic data in your file then the app may only be able to provide a partial analysis of some of the rare diseases that are analyzed by this app. This is more likely to occur if your genetic data file is from a company or laboratory that uses DNA microarray technology for their genetic testing, such as AncestryDNA, 23andMe, MyHeritage, and FamilyTreeDNA.

If you think a loved one may be at risk, one of the best things to do is to get whole genome sequence (WGS). WGS is a simple process and you can order a testing kit that is mailed to your home. Simply spit in the kit, mail it back to the lab and your genome will be sequenced within about a month.

Once you obtain your data from DNA testing or genome sequencing, you can then use the Rare Disease Screen app for ⁠genetic testing for disease and find an online genetic counseling service to discuss the results with a professional.