December 14, 2015: Genetic testing in facioscapulohumeral dystrophy

Interested in submitting an E-Pearl?
Brought to you by the Residents & Fellows Section of Neurology.

December 14, 2015

Genetic testing in facioscapulohumeral dystrophy

Facioscapulohumeral dystrophy (FSH) types 1 and 2 are phenotypically identical and characterized by progressive weakness and wasting of the face, shoulders, and upper arms. Over time, weakness spreads to the torso and legs and patients can develop hearing loss and cardiac arrythmias. In FSH Type 1, there is a contraction of D4Z4 microsatellite repeats on the long arm of chromosome 4, leading to expression of the protein DUX, a homeobox gene, in skeletal muscle.1 FSH Type 2 is characterized by mutations in the SMCHD1 gene, resulting in decreased methylation of the D4Z4 region.2 The genetic diagnosis for FSH Type 1 includes southern blot analysis for deletions on the long arm of chromosome 4. For FSH Type 2, patients can undergo methylation assays and sequencing of the SMCHD1 gene.

  1. Lemmers RJ, van der Vliet PJ, Klooster R, et al. A unifying genetic model for facioscapulohumeral muscular dystrophy. Science 2010; 329: 1650-1653.
  2. Lemmers RJ, Tawil R, Petek LM, et al. Digenic inheritance of an SMCHD1 mutation and an FSHD-permissive D4Z4 allele causes facioscapulohumeral muscular dystrophy type 2. Nat Genet 2012; 44: 1370-1374.

Submitted by Adam Numis, MD, University of California, Los Angeles.

Disclosures: Dr. Numis is a member of the Resident and Fellow Section of Neurology.

For more clinical pearls and other articles of interest to neurology trainees, visit Neurology. Listen to this week's Neurology Podcast.


Forgot password?

**Due to required system maintenance on, some functions may be unavailable Saturday from 1:00 p.m. to 6:00 p.m. Saturday (12/9/2017). Thank you for your patience.**