Facioscapulohumeral muscular dystrophy (FSHD) or Landouzy-Dejerine dystrophy is the third most common muscular dystrophy, after Duchenne muscular dystrophy and myotonic dystrophy, with an estimated prevalence of 1:8,000 to 1:20,000. FSHD is an autosomal dominant genetic disease with variable penetrance, which manifests frequently in the second decade of life, but can begin in infancy or later in adulthood. Life expectancy is not shortened.
The first clinical description provided in 1884 comes from Landouzy and Dejerine report. More than 100 years later, in the 1990s, the correlation between FSHD and the subtelomeric region of chromosome 4q35 was established.
This region contains a tandemly repeated unit called D4Z4. Each of those units consists of 3.3 thousand base pairs. D4Z4 repeats contain some coding sequences, of which the sequence of polyadenylation signal for retrogene double homeobox 4 (DUX4) mRNA was found to be the causative factor for FSHD pathology. Thus, the symptoms of the disease are caused by mutations affecting the D4Z4 array permitting the expression of the DUX4. However, the detailed mechanism of DUX4-elicited myodystrophic changes is still debatable. Currently, due to two different mechanisms leading to the development of the disease, types of FSHD1 and FSHD2 are distinguished.
The disease distinguishes by a particular distribution of muscle impairment affecting facial and shoulder girdle muscles. Moreover, sometimes weakness in the abdominal muscles occurs, which can cause severe hyperlordosis. Additionally, lower limbs can be affected, usually beginning from the tibialis anterior muscle impairment. Finally, with time weaknesses of proximal leg muscles may develop.
Extramuscular manifestations are not usually found. However, retinal vasculopathy, hearing loss, and rarely cardiac arrhythmias can be detected by various tests. Fortunately, their course is primarily mild or subclinical.
DUX4