SUMMARY
Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant muscle disease
that affects males and females of all ages. FSHD is thought to be the third most prevalent
muscular dystrophy (~12:100,000 adults); however, due to variable severity and complications
with genetic testing, many people remain undiagnosed and the prevalence may be significantly
higher. The clinical diagnosis of FSHD by a neurologist can be complicated by the variability of
disease presentation, and is often misdiagnosed as a limb-girdle type muscular dystrophy or a
simple chronic injury. Standard genetic testing for neuromuscular disease using gene-specific
targeted sequencing panels or even whole exome sequencing does not identify FSHD1
(representing >95% of FSHD cases) and can easily miss FSHD2 (<5% of cases). Following
clinical diagnosis, genetic testing is expensive and not accessible to many populations. Thus,
due to a combination of late onset, slow progression of weakness, highly variable clinical
presentation, and lack of access to or knowledge of specific genetic testing, many FSHD
individuals remain undiagnosed for years and the disease runs through families, affecting
multiple members across several generations. In addition, since current genetic testing for
FSHD is costly, time-consuming, complex, incomplete, and incompatible with standard genetic
testing techniques for other neuromuscular diseases, we know very little about the prevalence of
FSHD in many parts of the world as well as in certain ethnic and underserved populations even
within the US. To address this need, we recently developed a novel diagnostic test for all forms
of FSHD based on the epigenetic status of the disease locus. This analysis can be performed
on genomic DNA from any source, including saliva, and of almost any quality, thereby making it
widely available and accessible to family members of any age and people around the world in
underserved communities. Here, we will convert the current diagnostic protocol from low-
throughput single use to a high-throughput next-generation sequencing protocol. This transition
will greatly reduce the cost of the assay and render it more amenable to meeting CLIA approval.
In addition, we are collaborating with the MOVE FSHD study and performing epigenetic analysis
on all 250 participants. These subjects will have in-depth clinical evaluations and documented
natural histories which will allow us to determine if epigenetic profiles of the disease locus can
serve as a prognostic biomarker for FSHD.