Symptom Severity in Rare Disease Varies by Patients: Genetics May be to Blame

Geisinger was founded by Abigail Geisinger over 100 years ago. It now has 13 hospitals and 2 research centers. They just released a new study examining the severity of symptoms from patient to patient in rare diseases. Specifically, 11 rare conditions were examined to understand “variable expressivity.” This particular study was led by Matt Oetjens (Lead Author), Christa Martin, and David Ledbetter. It was published in October in Nature Communications.

The symptoms of rare diseases like cystic fibrosis and sickle cell anemia vary dramatically from patient to patient. This reigns true even for individuals who are in the same family.

For example, Turner syndrome patients are typically very short, and this characteristic is evident by the time the patient is five years old. However, for those with tall parents, this symptom may not be as evident. As a result, diagnosis and treatment are delayed for the patient.

Understanding how and why these symptoms vary can help physicians better treat their patients. This could improve not only patients’ prognosis, but their quality of life as a whole.

So how exactly did they complete this study which included so many different diseases? They used MyCode.


MyCode is the largest database from any one healthcare system in the entire world. It was created by Geisinger and currently has information on over 92,000 patients. It’s primary aim is to help identify the genetic risk of participants in order to diagnose conditions earlier and get patients treated faster.


In this latest study, the research team utilized polygenic scores (PGS). This score helps to measure the various ways genetic diseases may be expressed in the body. They identified 600 patients who were all unrelated to one another. Each had one of 11 different rare diseases. Each of these diseases affected either height, weight, or cholesterol levels, which are common genetic characteristics.

This investigation helps to show that we can’t only evaluate the single genetic cause of a disease. If we evaluate other genomic information simultaneously, using PGS scores, we may be able to accelerate the speed of care for patients.

They hope that PGS will become widespread, allowing physicians to better predict severity of symptoms for individuals, guide their analysis of the right preventative care measures, and minimize overall patient risk.

Ultimately, this research team believes that by implementing PGS scores, we will be able to make precision medicine more effective for a multitude of rare patient populations.

You can read more about this study here.

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