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Facioscapulohumeral muscular dystrophy

Basil T Darras, MD
Section Editors
Douglas R Nordli, Jr, MD
Jeremy M Shefner, MD, PhD
Deputy Editor
John F Dashe, MD, PhD


The muscular dystrophies are an inherited group of progressive myopathic disorders resulting from defects in a number of genes required for normal muscle function. Some of the genes responsible for these conditions have been identified. Muscle weakness is the primary symptom.

Facioscapulohumeral muscular dystrophy (FSHD) is the third most common type of muscular dystrophy. It is a complex genetic disorder characterized in most cases by slowly progressive muscle weakness involving the facial, scapular, upper arm, lower leg, and hip girdle muscles, usually with asymmetric involvement.

The clinical aspects of facioscapulohumeral muscular dystrophies are discussed here. Other muscular dystrophies are presented separately. (See "Clinical features and diagnosis of Duchenne and Becker muscular dystrophy" and "Emery-Dreifuss muscular dystrophy" and "Limb-girdle muscular dystrophy" and "Myotonic dystrophy: Etiology, clinical features, and diagnosis" and "Oculopharyngeal, distal, and congenital muscular dystrophies".)


Although the precise details are not entirely resolved, the most probable cause of FSHD is inappropriate expression of the double homeobox protein 4 gene (DUX4) [1,2]. The DUX4 gene lies within a macrosatellite array known as D4Z4, located in the 4q35 region. The DUX4 gene is normally expressed in germ line tissue and is epigenetically repressed in somatic cells [3]. Release of DUX4 repression only occurs in the context of a permissive genetic background.

In approximately 95 percent of patients with FSHD, the disorder is causally related to a short repeat array that remains after deletion of an integral number of tandemly arrayed 3.3 kb repeat units (called D4Z4) in the 4q35 region (figure 1) [2,4,5]. The number of D4Z4 repeat units in the general population varies from 11 to 100. In most patients with FSHD, one D4Z4 allele is contracted (1 to 10 repeat units; EcoRI fragments <38 kb; EcoRI/BlnI fragments <35 kb), and the other D4Z4 allele has the normal number (11 to 100 repeat units), a condition termed FSHD1. Contracted D4Z4 repeat arrays have been associated with DNA hypomethylation and a reduction of histone 3 lysine 9 trimethylation and heterochromatin protein 1gamma markers, favoring a more relaxed chromatin structure [6,7]. Thus, D4Z4 contractions may affect adjacent gene expression by altering chromatin configuration [8].

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Literature review current through: Nov 2017. | This topic last updated: Jan 16, 2016.
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