JS-LIFE Research Challenge

Research Plan

Ann Chang's picture
Discussion Topic Status: 
Open for Discussion

Study Aims and Significance

Joubert syndrome (JS) is a rare genetic disorder characterized by a specific brain malformation, low muscle tone and intellectual disability.  It may also affect other organs including the eyes, kidneys, and liver. Although estimated to occur in every 1/80,000 to 1/100,000 births, JS is likely more common due to overlapping features with other disorders affecting brain development. JS is often diagnosed after a long and costly search for an answer for families of affected children. Once diagnosed, there is limited information about the clinical course of the disorder and health care guidelines are outdated.

In order to better inform providers and families, we want to identify the early diagnostic features of JS while redefining the spectrum of clinical symptoms.  Information will be gathered from the Joubert Syndrome and Related Disorders Foundation (JSRDF) patient database (Joubert Syndrome Link to Information and Family Exchange (JS-LIFE)) and crowd-sourcing platform Mosaic which allows clinical researchers, providers, family members and caregivers the opportunity to share their experiences regarding JS.

Through this research study we aim to provide guidelines for early diagnosis and screening as well as annual management recommendations to allow for the best possible developmental and health outcomes.

Aim 1 To identify early diagnostic features of Joubert syndrome.

JS is currently a clinical diagnosis based on MRI findings (the Molar Tooth Sign) and accompanying clinical features. Advances in technology have also led to the identification of mutations in several genes associated with JS. We will investigate how families received a diagnosis using the JSRDF information database. This study will lead to the development of updated diagnostic criteria for JS, providing early and accurate diagnoses that will impact timeliness of appropriate therapies and screening for associated health problems.

Aim 2 To characterize the clinical manifestations of Joubert syndrome

JS affects multiple organ systems to varying degrees resulting in a wide spectrum of clinical presentations. More common findings include intellectual disability and behavioral differences, retinal defects, renal and liver disease.  We will investigate these symptoms, their clinical course and treatments in the JSRDF database. This study will lead to updated management guidelines documenting the frequency of screening and optimal medical and supportive care for complications associated with JS.

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Karen Tompkins's picture

This looks great :)  I'm excited to start mining!  

In regards to the JS-LIFE data:  should we be including a campaign to increase participation and/or survey completion... or is this just in the JSRDF's purview?

Also: updated management guidelines documenting the frequency.  What guidelines are we going to refer to? Should we include those in the plan?



Matthew Smith's picture

Absolutely, Karen! From the superficial data mining we have done, we already know that we need a more complete data set. We may also need to contact individuals who we would need more information on specific sets of data in order to include their record in the studies.

For updated management guidelines, we hope to build upon and contribute to those discussed during the medical advisors' panel at next week's JSRDF Family and Medical Conference. We will absolutely build into the plan.


July 24, 4-5pm Central | Panel Presentations of Updated Healthcare Recommendations:

The healthcare providers attending the conference will discuss updated recommendations for evaluation, monitoring, and treatment of individuals with Joubert syndrome. Moderated by Dan Doherty, MD, PhD.


I know that Dr. Doherty has a draft of these recommendations in place and hopes to publish soon.

Susan Friedman's picture

So happy to read what JS-Life has in the works - it's very exciting!  Optimal medical care is key in those with this disorder (and variants of the disorder). Physician Education is a must and, very much needed all across the Country so that, individuals can receive the best and most timely care available to them.

Joshua Bear's picture

These seem like great initial research questions. Regarding Aim 1, I'm wondering what aspect of "how families received a diagnosis" will be evaluated in order to help update the diagnostic criteria. Will it focus the clinical features that raised the suspicion (similar to aim 2)? Or a qualitative evaluation of the experience and time frame, also important but less likely to help define diagnostic criteria? The comment on the breadth of genes suggests some focus there, but it might be valuable to have diagnostic criteria to help guide the decision to pursue genetic testing rather than relying on the genetic testing at the onset.

Maura Ruzhnikov's picture

Hi Josh! Regarding Aim 1, we are hoping to refine the current clinical diagnostic criteria by looking at what clinical attributes led to a diagnosis-- ie for those who received an early diagnosis via prenatal ultrasound, what was seen on the ultrasound and postnatal imaging-- and getting to your follow-up question, do we then have enough information to go forward with targeted genetic testing rather than waiting for years for additional clinical symptoms to arise before a diagnosis is made? Aim 1 will be separate from Aim 2 in that Aim 2 is more focused on defining the natural history of the spectrum of JS with the hopes of updating management guidelines while Aim 1 is really focusing on earlier and more specific diagnostic criteria.

Brett Elliott's picture

I think that sounds perfect, can't wait to see how the data adds up! In what ways do we plan on getting the additional data from patients in Aim 1 such as prenatal imaging etc.  And are we confirming only Joubert syndrome patients are included in the study by reviewing MRI or medical records?  If so how do we inspire participation beyond our initial JS-Life participation to get this data?

Matthew Smith's picture

It is going to be exciting to see what can be learned from the aggregated data in JS-LIFE. For this study, we will be using the current information of JS-LIFE participants, from the initial survey. We will follow-up as necessary to confirm and/or clarify the data points necessary to make this a great study. Obtaining imaging and medical records for confirmatory review will be part of a Phase II push with the JS-LIFE 2.0 survey to be released in the coming months. Perhaps we could do a new study in Mosaic on imaging alone!


The new JS-LIFE survey has imaging and records upload questions built in to the participants' living health record and will allow for follow-ups and review by research teams, as privacy setting allow. JS-LIFE 2.0 will be on a new PEER system that allows longitudinal entry and update of answers by participants over time, allowing them to keep track of their medical records and to chart their progress over time. Over the years and especially through CENA, we have found that we have an amazing community that is willing to share for the advancement research, and the inspiration to come back and participate beyond the initial JS-LIFE push should go hand and hand with the additional features in JS-LIFE 2.0. The new system will have automated reminders for individuals to come back and alerts of new survey components, such as the imaging and medical records mentioned above. We will be able to easily "ping" participants to come back to update their information with these valuable components that really complete the full picture.