mTOR Related Disorder and Smith-Kingsmore Syndrome (SKS)

On August 21, 2019, Ezra received the diagnosis of "mTOR Related Disorder" by the Undiagnosed Diseases Network (UDN) at Duke University Hospital. We were told that Ezra was the fifth known (at that time) to have a specific mTOR gene variant, named p.Thr1977Ile. It's been six months since his diagnosis. During this time, we have been processing, learning, researching and connecting with other families with a similar diagnosis. 

Ezra, 3 years old

On diagnosis day, our UDN geneticist explained to us that the diagnosis, mTOR related disorder, is a broad and generic term referring to mutations in the mTOR gene (which is responsible for a ton of things!). He did his best to explain all that he knew, based on the very limited research about Ezra's gene variant. The geneticist had two research papers and handed them to us. One was published in July 2016 (coincidentally the same year Ezra was born) which documented the first three individuals, and the other was published in April 2019, with the fourth. Needless to say, not much information was out there.

No doubt after seeing the deflated look on our faces, the geneticist quickly started telling us about another rare mTOR related disorder, called Smith-Kingsmore Syndrome (SKS). He shared with us that while there are several differences, Ezra's diagnosis is very similar to SKS. He suggested we start there and try to learn what we could about SKS.

So we did just that.

I immediately found there was a Facebook support group and a Smith-Kingsmore Syndrome (SKS) website! The website was filled with beautiful little faces, and a few that even resembled Ezra! I was elated and confused at the same time.

I started gobbling up all of the information on the website and Facebook page learning about these SKS families who had similar struggles as us. SKS is a newly discovered disorder (it was first published in 2013) and recognizes several different gene variants which fall under SKS. It is a rare genetic disorder and at that time a little over 40 individuals were diagnosed. Amongst my research, I also learned about a conference that was to be held in October at Cincinnati Children's Hospital, Ohio. The "Inaugural Smith-Kingsmore Syndrome Conference". 

Eric and I decided to make the trip to Cincinnati so we could learn even more than what we had doing personal research. There was a group of pediatric specialists who had taken a special interest in SKS. I emailed the conference coordinator to inquire and the next thing I knew I received an email from the geneticist himself who would be leading the conference. He was very excited to hear about Ezra's gene variant and encouraged us if we could, to come and be a part of the conference. 

Fast forward to October 2019; The two day conference was everything to us! The first day consisted of one-on-one appointments with the lead pediatric specialists of the conference. The doctors were eager to meet Ezra, our family, and hear about Ezra's journey. One of the questions I had for the geneticist was whether or not he thought Ezra had SKS. I shared with him that I noticed that none of the other SKS individuals appeared to have Mosaicism like Ezra. He agreed that mosaicism was quite rare and probably made it harder to diagnose. The doctor also shared with us that he felt Ezra indeed had a Mosaic form of Smith-Kingsmore Syndrome. He believed that in time, the research will support his hypothesis. I was stunned by his conviction. He also carefully explained to Eric and I that because Ezra is mosaic, his symptoms may be more severe.

The second day of the conference was even better than the first. Not only did we get to meet Dr. Laurie Smith of Smith-Kingsmore Syndrome, we got to meet all of the amazing SKS families! They were there for the same reasons as us - they too were seeking all of the precious information that was presented. There were about 20 or so families that came from all over the world!

Inaugural Smith-Kingsmore Syndrome Conference 2019,
Cincinnati Children's Hospital, OH

Dr. Laurie Smith, Smith-Kingsmore Syndrome

Cincinnati Children's Hospital Specialists, invested in researching Smith-Kingsmore Syndrome

In the months after the conference, Eric and I have a renewed purpose. It's taken me some time to come to terms with the possibility of Ezra having a mosaic form of SKS. However, the more I think about it; the more I research it; the more I look at these beautiful SKS faces; the more I am slowly coming to believe that Ezra might very well have Mosaic SKS. I'll tell you what though, if there was a disorder that Ezra had to fall under, Smith-Kingsmore Syndrome would be it. I couldn't be more proud to know these families and be a part of a community that is filled with a fierce love and drive for (our) SKS kids.

** There are now six known individuals with the gene variant p.Thr1977Ile. All six have Mosaicism.