The Value of a Diagnosis

The most common utility for whole genome sequencing currently is to diagnose unknown diseases, syndromic diseases or those diseases that manifest similarly to known disorders, but don’t respond well to traditional treatment. As clinical geneticist David Bick describes, these disorders are “three degrees of separation from what you expect.”

Particularly in cases of rare undiagnosed disorders, patients arrive at a genomic medicine clinic after a diagnostic odyssey that has lasted seven years or more, involved dozens of specialists at multiple hospitals, and has cost upwards of five figures… or more… and they still don’t have an actual answer about the cause of their disorder.

“A diagnosis is incredibly important because it gives us a place to work from,” said David Bick, MD, a clinical geneticist at The Smith Family Clinic for Genomic Medicine. “If I don’t know what’s wrong, I can’t treat it.”

That is proving especially true for disorders that have descriptions, but no clear molecular diagnosis. Seizure disorders, for example, are characterized by regular or irregular seizure activity, but have many different causes. Therefore, patients respond very differently to medications prescribed to attempt to treat the seizures. These patients are not rare. In North Alabama, a single neurology clinic led by Dr. Martina Bebin has delivered 150 genomic diagnoses to children with intellectual disability, thanks to a research program at HudsonAlpha. How do we offer this to more clinics and help more patients?

Another example is congenital heart defects. The most common birth defect, it is present in more than 500 different syndromes. Identifying a genetic cause for the CHD could lead to a new or different treatment strategy.

Even in cases in which there is no treatment for a disorder, patient families believe the diagnosis itself is incredibly meaningful and stops the need to keep searching for an answer. It also enables the care team to stop trying different treatment strategies in hopes of one working. Further, the lack of treatment today doesn’t necessarily mean there won’t be an effective treatment coming to market in the future.

There is also great utility in family knowledge of the etiology of a disease. In cases of heritable disorders, once a causative gene variant is identified, additional family members may be tested to identify potential future health challenges for them, or for their children.

Some examples:

Mindy Brayman is parent to two boys – Jack and Todd – with a rare disease. She finally received a diagnosis through genomic sequencing, and though she learned there are no additional treatments, she said she also now knows it isn’t something she caused.

“As we suspected, it is a very rare disorder without much information to help. Less than 20 kids have ever been found with this mutation. It also confirms we haven’t done anything wrong for the boys, and the most we could do is be sure they have good lives,” she said.

Jack passed away before she learned of Todd’s diagnosis. Todd is now scheduled for a Make-A-Wish trip in May.

Cindy Jones of Huntsville also is a parent to at least two sons with a very rare form of high cholesterol. For her, a molecular diagnosis was important for multiple reasons.

“I needed the diagnosis confirmed, and that felt like a relief to just get that answer. But it also gave us a place to look for the rest of our family. What if there are other family members who are affected?” she reflected.

Jones began a foundation for her sons’ condition, sitosterolemia.

“I’m so glad there is a treatment, but what about all the people out there who don’t know why their high cholesterol isn’t responding to regular medications? To me, that’s why it is so important to get a diagnosis and a cause. This could save lives,” she believes.

Gina Szjanuk, parent to three children with a rare undiagnosed condition – and a patient herself – founded the Rare Undiagnosed Network (RUN) with one ultimate goal: give families answers. End the diagnostic odyssey. She is still waiting, but is hopeful that whole genome sequencing through the National Institutes of Health’s Undiagnosed Disease Program (UDP) will find those long-awaited answers. HudsonAlpha Institute for Biotechnology is the Clinical Sequencing Laboratory for Whole Genome Sequencing for the UDP.

“Our diagnostic journey continues on. We have been to eight hospitals in five states, but we are so blessed and thankful to have amazing teams around the country focusing on our family. Thank you from the bottom of our hearts. We will continue to pray for a miracle in 2017.”

Clinicians: If you have a case that does not fit the clinical picture for the most likely diagnosis, we would be happy to see them at the Smith Family Clinic to determine if a molecular test could help. Additionally, the HudsonAlpha Clinical Services Lab provides an end-to-end genomic solution that begins with a blood sample. From there, the sample is sequenced and interpreted. A detailed clinical report of the findings is returned to the physician.