Hi All! This note is for *pediatric* patients only (including those who are adults now, but were diagnosed as children), although we are sending well wishes and hugs to everyone from North Carolina. Xx
I have been in touch with Dr. Richard (Rick) Pierce from Yale University with exciting news about taking a closer look at genetic sequencing for kiddos with SCLS. (thank you to Whitney Turner Septon for expediting our notes in his inbox).
In sharing Reverie's story with Dr. Pierce I expressed my interest in needing to do a better job at educating major U.S. PICUs and perhaps major children's hospitals around the US about SCLS. While the disease is incredibly rare, the presentation is so simple and identical in every single case (periorbital edema, hypoalbumenia, tachycardia, hypotensive). I believe we have the ability to save another child's life by simply informing major US hospitals about the presentation and symptoms of SCLS. I am aware of 3 pediatric cases that developed following 2021 Covid infections; I imagine there are several others out there right now who are on the same runaround journey we all were with Allergy/ENT, etc.
Well, HE LISTENED. And I received the best email:
"I am working on putting together an awareness campaign and educational module on the diagnosis and inpatient treatment of pediatric SCLS. As part of this campaign, we would love to include patient and family stories. We are working with Yale's Department of Pediatrics media team and Yale's media production teams.
On November 25, we are doing an interview with Yale's Media Team to tell the story of Reverie's diagnosis and treatment.
Dr. Pierce's team also feels there is a genetic component to SCLS and investigated eight pediatric SCLS patients with genetic sequencing through Yale's Pediatric Genomic Discovery Program (manuscript attached). Unfortunately, they did not find any single genetic abnormality that could explain all pediatric cases of SCLS. However, it was only 8 patients and they are always keen to sequence other patients. They also did the analysis in 2018 and have learned more about SCLS; they can re-analyze all of our data to see if something new comes up.
Please let me know if you and your child are willing to participate in the genetic sequencing, the more samples the better. I will put you in touch with the study admin at Yale, Monica. It is a very simple saliva test (no cost to participate)
They are waiting to sequence all samples to reduce confounding batch effects.
With Love,
Jordan, George & Reverie
PS: I do have a PDF copy of the 2018 study if anyone would like to see it.
https://www.yalemedicine.org/departments/pediatric-genomics
Jordan, congratulations on such a great initiative you have been pursuing!
Dr. Pierce and colleagues have already published 3 research pieces on SCLS, so I'm pretty sure that he knows what he's doing.
The highly technical articles can be viewed at https://rupress.org/jem/article/214/12/3497/42272/A-p190BRhoGAP-mutation-and-prolonged-RhoB (2017), https://journals.lww.com/pccmjournal/abstract/2018/07000/sera_from_children_after_cardiopulmonary_bypass.2.aspx (2018), and https://journals.lww.com/shockjournal/fulltext/2019/08000/whole_exome_sequencing_of_adult_and_pediatric.7.aspx (2019). Dr. Druey was one of Pierce's coauthors in this last one.
Dr. Druey and two co-authors have just published a comprehensive primer on SCLS, both primary (ISCLS -- the kind we in this community have) and secondary (SSCLS), to which I dedicate a separate Topic entry here in our RareShare home, see https://rareshare.org/topics/2260, and they cite Pierce's three aforementioned articles, see https://www.nature.com/articles/s41572-024-00571-5.pdf
In case he hasn't seen it, please mention the publication of this primer to Dr. Pierce, because there is research advice in it for him: "Because preliminary analysis has thus far failed to uncover shared exomic aetiologies in adult patients [Pierce’s 2019 article cited here], further scrutiny of non-coding DNA sequences is warranted. The discovery of autonomous and durable functional defects in MG-CLS-derived endothelial cells points to the possibility of de novo somatic mutations limited to the endothelium. In contrast, de novo germline mutations are more likely in children such as the potentially pathogenic mutations in ARHGAP5."