Facioscapulohumeral Muscular Dystrophy Type 2

Abstract

Facioscapulohumeral muscular dystrophy (FSHD) is characterized by progressive muscle weakness with focal involvement of the facial, shoulder, and arm muscles. Muscle weakness first affects the facial muscles and upper extremities and later progresses to involve the lower extremities. The pattern of weakness is usually asymmetric. The onset of symptoms occurs between 3 and 50 years of age. Early onset of the disease is associated with more widespread muscle weakness. Although facial weakness (difficulties whistling, smiling, and closing the eyes) is an early feature, the shoulder muscle involvement (difficulties lifting the arms, scapular winging, and sloping shoulders) is the most frequent patients’ complaint.

Muscle involvement progressively affects wrist extension, the abdominal muscles, knee, and foot extensor muscles. Sensory, cardiac, and neurological signs are rare.

FSHD is a dominant inherited disorder presenting genetic heterogeneity. FSHD type 2 shows digenic inheritance, since it is caused by the combination of a heterozygous mutation in the SMCHD1 gene and presence of a haplotype on chromosome 4 that is permissive for DUX4 expression. Sacconi et al. found that mutation in the SMCHD1 gene is a modifier of disease severity in patients with FSHD1. FSHD type 1 and type 2 are clinically indistinguishable, and the disease mechanisms of FSHD1 and FSHD2 converge at the level of D4Z4 chromatin relaxation and variegated expression of DUX4 in skeletal muscle.