Facioscapulohumeral muscular dystrophy (FSHD), caused by partial deletion of the D4Z4 macrosatellite repeat on chromosome 4q, has a complex genetic and epigenetic etiology. To develop FSHD, D4Z4 contraction needs to occur on a specific genetic background. Only contractions associated with the 4qA161 haplotype cause FSHD.

Several genes have been examined as candidates for causing FSHD, including the DUX4 homeobox gene in the D4Z4 repeat, but none have been definitively shown to cause the disease, or has the full extent of transcripts from the D4Z4 region been carefully characterized.

Research on the cause and treatment of facioscapulohumeral muscular dystrophy (FSHD) might be entering a new, and hopefully better, era. For many years FSHD has been a difficult disease for medical researchers to study. In most genetic diseases, a gene with some known function is mutated and no longer performs its normal biological role. To find a treatment for such a disease, the medical researcher needs to identify therapeutic interventions that will compensate for the mutant gene.