Genetic Testing for Rare Diseases with Sequencing.com

In this article we explain what a rare disease is, give some examples, and look at how Sequencing's Next-Gen Disease Screen can analyze your DNA for more than 15,000 rare diseases, syndromes, conditions, and traits.

What is a rare disease?

A rare disease is a disorder or condition that affects a small share of the population at any given time. In the United States, a disease is considered rare if it affects fewer than 200,000 people. In the European Union, the threshold is fewer than 1 in 2,000 people.

Rare diseases are sometimes called orphan diseases, a term tied to the US Orphan Drug Act of 1983, which created incentives to develop treatments for these conditions.

Rare diseases can be inherited or not. Most are thought to be inherited, meaning they are caused by changes in genes or chromosomes. Many are progressive and some are disabling. Diagnosis is often difficult, and clinicians frequently order genetic tests to confirm a diagnosis. Earlier diagnosis can lead to earlier care, which may reduce the risk of long term complications.

How many rare diseases are there?

There are thousands of known rare diseases, and more are identified every year. Because most are caused by changes in a person's DNA, genetic testing methods such as exome sequencing and whole genome sequencing have become among the most important tools for detecting them.

If you think you or a loved one may have a rare disease, genetic counseling can help you decide which DNA test is most appropriate, and can help you understand a genetic report or the results from DNA apps. The Partner Marketplace includes a Genetic Counseling app for this.

If you have already taken a DNA test, for example from 23andMe, AncestryDNA, GeneDx, or Ambry Genetics, apps that focus on rare disease detection can analyze that data. These apps work with raw data from a wide range of genetic tests and from genome sequencing. We cover them further below.

Examples of rare genetic diseases

Naxos disease

Naxos disease is an inherited condition that combines a heart muscle disorder (arrhythmogenic right ventricular cardiomyopathy) with distinctive woolly hair and thickened skin on the palms and soles (palmoplantar keratoderma). Carvajal syndrome is a related variant. People with Naxos disease have an elevated risk of dangerous heart rhythms, so cardiology care and monitoring are important. It illustrates a key point: when a rare disease is identified accurately, its impact can sometimes be reduced through preventive measures.

Rippling muscle disease

Rippling muscle disease primarily affects the muscles. It causes increased muscle irritability, producing visible ripples that move across skeletal muscle in response to stretch, pressure, or movement. The muscles closest to the center of the body are most often affected. Signs typically begin in late childhood or adolescence, and management is based on the specific symptoms and their severity.

Caffey disease

Caffey disease, also known as infantile cortical hyperostosis, most often occurs in infants. It involves inflammation and excessive new bone formation, leading to bone changes in the jaw, shoulder blades, collarbones, and the shafts of long bones in the limbs. Affected babies may have fever, irritability, pain, and soft tissue swelling. Symptoms often resolve on their own.

Fish eye disease

Fish eye disease, also called partial LCAT deficiency, affects the corneas at the front of the eyes and causes them to become cloudy. This clouding can significantly impair vision. Management depends on the symptoms in each person, and in severe cases a corneal transplant may be considered.

Muscle eye brain disease

Muscle eye brain disease is an inherited degenerative disorder associated with developmental delay and intellectual disability. Signs vary between individuals but often include low muscle tone, eye problems such as glaucoma, and brain abnormalities. It is caused by changes in the POMGNT1 gene. There is no cure, and treatment focuses on managing symptoms and supporting quality of life.

Thin basement membrane disease

This inherited kidney condition affects the glomeruli, the clusters of tiny blood vessels that filter the kidneys. Some people have small amounts of blood in the urine with no other symptoms and remain healthy throughout life, while others can develop more significant kidney disease.

How can I test for rare diseases?

If you are concerned that a loved one may have, or may pass on, a rare disease, DNA testing and analysis can help. A DNA test can show that you carry a variant for a rare disease, meaning you are not affected yourself but your children could be.

With the Next-Gen Disease Screen on Sequencing, you can analyze your DNA for more than 15,000 rare diseases, syndromes, conditions, and traits.

How completely the app can analyze each item depends on how much genetic data is in your file. If your file does not contain enough data, the app may only be able to partially analyze some conditions. This is more likely when the file comes from a company that uses DNA microarray technology, such as AncestryDNA, 23andMe, MyHeritage, and FamilyTreeDNA, because those tests read only a small portion of your DNA.

For the most complete analysis, the best option is whole genome sequencing, which reads 100% of your DNA and all of your over 30,000 genes. It is a straightforward process. You order a kit that is mailed to your home, provide a sample, mail it back, and your genome is sequenced, typically within about a month.

Once you have your data from a DNA test or from genome sequencing, you can run the Next-Gen Disease Screen and, if you would like to discuss your results, use the Genetic Counseling app in the Partner Marketplace to speak with a professional.