Progress Update: Optimizing the Utility of the National Registry for FSHD Research and Trial Recruitment

Report by Dr. Rabi Tawil

See grant Optimizing the Utility of the National Registry for FSHD Research and Trial Recruitment

Aims: The aim of the study is to offer participants of the NIH National Registry of FSHD Patients, who have not been genetically confirmed, the chance to get detailed genetic testing for both FSHD1 and FSHD2. This will significantly enhance the value of the Registry both for the participants and for the FSHD research community.

Lay Summary

A significant percentage of individuals with FSHD in the National FSHD Registry have not had genetic testing to confirm their diagnosis. Genetic confirmation is important for the value of the data in the registry but most importantly, all future clinical trials will require that individuals interested in joining a drug trial be genetically confirmed. We have so far been able to test 83 individuals with FSHD.


The study involves a collaborative effort between the University of Rochester Medical Center (URMC) FSHD research team, the National Registry team based in Rochester and the laboratory of Dr. Silvere van der Maarel at Leiden University Medical Center (LUMC). Funding was provided via a three year grant supported by the FSHD Society and Friends of FSH (6/1/2016 to 5/31/2019).

The capacity of LUMC to perform detailed genetic testing for this study is about 30-40 samples per year. The overall goal was to enroll 90-120 members of the Registry into this study. In order of descending priority, the following Registry participants were planned to be recruited:

  • Group 1: Clinically definite/probable FSHD, genetic testing not done (approximately 205 eligible members);
  • Group 2: Clinically definite/probable FSHD, genetic testing indeterminate for FSHD1 (approximately 30 eligible members, who may likely have FSHD2);
  • Group 3: Clinically definite/probable FSHD, genetic testing negative for FSHD1 (approximately 20 eligible members, who may likely have FSHD2).

Results to date

The study protocol was submitted for approval by the Registry Scientific Advisory Board and then to the University of Rochester IRB. IRB approval was obtained in October 2016. We sent multiple recruitment letters to over 210 Registry members from “Group 1” through the grant period. Only about 86 responded interested in getting genetic confirmation despite multiple mailings. We have, on the other hand offered genetic testing for new Registry enrollees who are not genetically tested, to get genetic confirmation. Earlier this year we were getting ready to send letters to individuals in “group 2 listed above” but that push was hampered by the COVID-19 pandemic during which having individuals get blood drawn for testing was difficult and shipping blood samples to Leiden in a timely fashion was not guaranteed. Enrollment and results are below:

  • 65 patients completed the study. Genetic test results have been shared with the patient and added to our Registry database. The results indicated 60 were positive for FSHD (55 patients had FSHD1, 2 had FSHD1+ FSHD2, 1 patient had FSHD2). Two patients were negative for and three patients had inconclusive results and are in the process of being re-tested by Leiden
  • Another 18 patients are in-process of: 1) providing consent; 2) receiving a blood collection kit, or; 3) providing a blood sample or 4) awaiting results of Leiden testing
  • With completion of testing of the 18 pending patients above we would have tested a total of 83 patients.
  • Another 23 patients contacted us with interest in the study but were found to have been tested previously, mostly from participation in research studies at the University of Rochester or that had been done clinically but that they were not aware of. We updated the Registry database accordingly for each subject, in effect enabling us to place an additional 23 registry patients into the genetically-confirmed category without having to test them.
  • All patients tested receive letters detailing the results of their genetic testing for future reference. Those with negative results also receive a letter describing their results. Additionally, I have reached out to those individuals by phone explaining the implication of their negative test and recommend that they return to their neurologist for a reevaluation of their diagnosis.
  • Our study has attracted the interest of researchers working on myotonic dystrophy (DM). Just like FSHD, the nature of genetic testing for DM not amenable to put as part of, readily available, often free, muscular dystrophy genetic panels and getting testing covered by insurance can be problematic. Consequently they are using our model to start a similar project to test patients with DM.

Future plans

  • In the final year of this grant, we will make a final push to reach our stated aim of testing between 90-120 individuals.
  • Carryover funds from the present year will be used for shipping blood kits and to pay Leiden for the testing done over the past year of funding.
  • We will also target new patients who are joining the registry and offer those who have not been genetically confirmed to get tested.