About Jordan's Syndrome (JS) or PPP2R5D-Related Neurodevelopmental Disorder
Jordan’s Syndrome is a neurodevelopmental disorder caused by variants, or mutations, in genes that encode parts of a protein complex called Protein Phosphatase 2A (PP2A). These genes include PPP2R5D, PPP2R5C, and PPP2R1A. This protein complex is a cellular machine that helps control biochemical processes in many different tissues of the body, including the brain. PP2A does this by acting as an on/off switch for other proteins involved in metabolism and cell growth. As a result, genetic variants associated with Jordan’s syndrome that impair the function of the PP2A complex may cause a spectrum of neurodevelopmental delays as well as low muscle tone, seizures, autism spectrum disorder, and ophthalmologic, skeletal, endocrine, cardiac, and genital anomalies. Because the PP2A complex is involved in so many processes in the body, it has also been implicated in Parkinson’s, Alzheimer’s disease and cancer.
PPP2R5D-related neurodevelopmental disorder is inherited in an autosomal dominant manner, meaning each pregnancy of an affected individual has a 50% chance of inheriting their pathogenic variant in the PPP2R5D gene. Most cases of Jordan’s syndrome reported to date are due to de novo genetic changes, meaning they were not inherited from a parent. For parents of an affected individual, the recurrence risk for future pregnancies is estimated at 1% due to the possibility of parental germline mosaicism.
Jordan's Guardian Angels Clinical Features
Since July 2018, the Jordan’s Guardian Angels Research Team has made remarkable progress related to deciphering the molecular mechanisms associated with Jordan’s Syndrome. The team has developed key tools, cell lines, mouse models, and structural insights to better understand the cellular functions and specific substrates for the PPP2R5D holoenzymes, as well as the pathobiology of the PPP2R5D variants.
The ultimate goal of the JGA team is to develop therapeutics to treat patients with Jordan’s Syndrome. We envision three different routes for treating genetic disorders such as Jordan’s Syndrome. One path is to “fix” the variant DNA by changing the mutated DNA base to a normal base. A second approach would be to identify the signal transduction pathways altered in cells expressing the variant PPP2R5D and then try to restore those signaling pathways to near normal using existing or new drugs. A third approach would be to identify drugs that specifically target the variant PPP2R5D holoenzyme (AB’δC) and restore normal function and regulation to the holoenzyme. All three approaches are simultaneously being developed by the JGA team, with excellent progress being made.
At this point, more than 250 people have been diagnosed with Jordan’s Syndrome in 35 countries. However, it is believed that some 200,000 people worldwide are affected but remain undiagnosed.
Get to Know Jordan's Guardian Angels
Jordan’s Guardian Angels is a Sacramento, California based non-profit foundation working to unlock some of our greatest medical mysteries. We are leading groundbreaking international research into Jordan’s Syndrome.
Founded in 2017 by Cynthia and Joe Lang, Jordan’s Guardian Angels’ mission is to conduct research seeking answers to rare genetic mutations affecting children and adults and assist and improve the quality of life for children and families. The Lang’s daughter Jordan was one of the very first children diagnosed with Jordan’s Syndrome. Together with world renowned Medical Investigator Wendy Chung, an incredible team of some of the best and brightest researchers across the globe at 10 top institutions was assembled and the research effort began.
To date, more than 250 families are now diagnosed with Jordan’s Syndrome and connected to a Facebook group to share ideas, stories, connect and feel a sense of family and community.
I am Especially Proud of...
At Jordan’s Guardian Angels we are especially proud of our unbelievable dream team of researchers. Their brilliant minds are working with their teams at 10 institutions across the world to find a treatment or a cure for Jordan’s Syndrome. The work that they are doing in collaboration with each other is nothing short of groundbreaking... it’s a true partnership that they all agreed to take part in, working as a team instead of as individuals. The speed that they are achieving their milestones is unbelievable, achieving in a few years what would usually take a decade.
We are also so proud of our global community growing in leaps and bounds every week. This special group of people motivates, supports, and loves so deeply and we are so proud to be able to bring them all together via Facebook, virtual and in-person conferences and more. The State of California also deserves our deep gratitude. We are so proud of their recognition of Jordan’s Syndrome and the work Jordan’s Guardian Angels is accomplishing. Vital funding has been allocated for the groundbreaking research being done, with lawmakers seeing in the research great hope that it will impact some of the world’s greatest medical mysteries.
We are also so proud of the strides we are making to raise awareness about Jordan’s Syndrome including our podcast ‘A Rare Reality’ which covers topics that are both Jordan’s Syndrome specific and rare disease broad. We welcome and covet the partnerships we are forming with those who are our guests on the podcast.
And we continue to be so proud of our families who are bravely navigating the loss of a child to Jordan’s Syndrome, including the family of Ozzie Deason. In honor of these children and all the children we have lost we have launched the Shine Like Ozzie Scholarship. The scholarship provides $1,000 to an undergraduate or postgrad student studying anything related to Epilepsy. We hope the light of our children taken too soon will forever shine.
Excited to REN Because...
We recognize the need for and the value of partnerships in the rare disease space.... together we are strong! We are excited to help create and share resources for our rare epilepsy families and the greater rare epilepsy community.
My Journey and Motivation...
Our motivation is and always will be the children, adults, and families affected by Jordan’s Syndrome.
For Jordan’s family and so many others it was years before a diagnosis finally happened. Now at 16 years old Jordan waits for a treatment or a cure for the rare disease that impacts her every single day.
For Ozzie’s family, they won’t be able to see the day when that treatment or cure could help their child, but they stand beside us and continue to support Jordan’s Guardian Angels even while dealing with immeasurable loss due to Jordan’s Syndrome and rare Epilepsy.
There are so many stories just like these. Beautiful faces that motivate our Jordan’s Guardian Angels team and team of researchers to work harder and faster than ever before, because there is a light at the end of the tunnel and so much hope for our families to look forward to.
We won’t stop. Together we truly can change the world.
By Brittany Cardoza, Assistant Project Manager, & Christina Janes, Director of Outreach and Awareness at Jordan's Guardian Angels