Integrating clinical and genetic observations in facioscapulohumeral muscular dystrophy

This review gives an overview of the currently known key clinical and (epi)genetic aspects of facioscapulohumeral muscular dystrophy (FSHD) and provides perspectives to facilitate future research.

Clinically, imaging studies have contributed to a detailed characterization of the FSHD phenotype, and a model is proposed with five stages of disease progression. A number of clinical trials have been conducted regarding exercise and diet aiming to reduce symptoms. Genetically, at least two different mechanisms (FSHD1 and FSHD2) lead to double homeobox 4 (DUX4) expression in skeletal myocytes, which is expected to be necessary for the disease. Disease severity is most likely determined by a combination of the D4Z4 repeat size and its epigenetic state.

FSHD is one of the most common muscular dystrophies and is characterized by a typical distribution of muscle weakness. Progress has been made on clinical as well as on (epi)genetic aspects of the disease. Currently, there is no cure available for FSHD. For successful development of new treatments targeting the disease process, integration of clinical and pathogenetic knowledge is essential. A clinical trial toolbox that consists of patient registries, biomarkers and clinical outcome measures will be required to effectively conduct future clinical trials.