Facioscapulohumeral Muscular Dystrophy
Ryan Edwards

Facioscapulohumeral muscular dystrophy (FSHD) is a rare autosomal dominant condition. FSHD, like all types of muscular dystrophy, is characterized by severe muscle degeneration. There are many forms of muscular dystrophy, each with specific characteristics and genetic causes. An affected individual has a fifty percent chance of passing the FSHD gene to their children. Miscarriages are not uncommon due to the complications involving the mutated germ cells. FSHD, with a frequency of one affected individual per 20,000 live births, is characterized by weakening muscles of the face, shoulder blade, and upper arm. The weakness is usually asymmetrical. Weakened face muscles are an early indicator of FSHD, as is difficulty in raising the arms. In addition, leg muscles can be weakened. Increased incidences of hearing loss and retinal disorders are witnessed in individuals with FSHD, yet this relationship is still unclear. For the most part, the heart is not affected, nor is the level of intelligence. This condition is generally less severe than other types of muscular dystrophy, yet can still be very debilitating. The severity of the condition largely depends on the age of onset. The earlier the symptoms develop, the more severe the disorder may become over time, due to its slow progression. However, in most cases, progression eventually levels off. Twenty percent of those with FSHD are at some point confined to a wheelchair. In addition, the range of expression is great. An affected infant may lose the ability to walk by adolescence, while another affected person may never suffer any handicap. In most cases, the traits are usually evident by the age of twenty.
The genetic cause of FSHD is a mutation in the 4q35-qter region, located near the end of chromosome 4. The location of the FSHD locus is still unknown, but researchers are using DNA markers to pinpoint it. Four markers, named D4S139, D4S171, D4S163, and F11, are being utilized. From the analysis of recombination events, the most likely gene order appears to be cen - D4S171 - F11 - D4S163 - D4S139 - FSHD - tel.(Sarfarazi, 1992). D4S139 is currently the closest known probe to the FSHD locus(Weiffenbach, 1992). Since D4S139 is more distal than D4S171, it appears that the FSHD gene is at the telomeric end of the group(Upadhyaya, 1992). However, one recombination event suggests that FSHD is proximal to D4S139(Wijmenga, 1992). More DNA markers that flank the FSHD gene are needed before anything is conclusive(Wijmenga, 1992). Also, additional probes in the 4q region are needed to identify the distance between the FSHD locus and the telomere. As more markers in the region are identified, flanking markers will be isolated. It is hopeful that someday the gene can be cloned(Weiffenbach, 1992).
It is interesting that many conditions involving facial dysmorphic features are believed to be due to a mutation of chromosome 4. Additional insight into understanding the gene involves using another probe. Researchers discovered that normal individuals have an EcoR1 fragment usually greater than 28kb, while individuals with FSHD have fragments measuring less than 28kb. This data suggests that a possible deletion of genetic material results in the mutation. FSHD, while usually inherited, can also result from a fresh mutation.
It is also possible that a homeobox gene may serve as the FSHD gene. Homeobox genes are highly conserved, present in most eukaryotes, and are responsible for segmental body development (Cummings). Since FSHD affects only certain muscles, largely those of the upper body, a homeotic mutation is a possible cause. Homeotic mutations cause tissue destined for a specific body part to alter its differentiation and form another structure. A translocation involving chromosome 21 and 4 supports this. It may be that the resulting breakpoint on chromosome 4 disrupts the FSHD gene or its regulatory elements. Thus, individuals develop early onset of facial weakness (Mathews, 1992). Individuals with FSHD have the proper appendages in the proper places, but the muscular wasting eventually leads to deformity. In this sense, the body structure is altered. That individuals with FSHD have normal intelligence lends further support to this type of homeotic mutation.
Facioscapulohumeral muscular dystrophy is a serious condition, but luckily does not affect lifespan. One type of muscular dystrophy that is more severe is Duchenne muscular dystrophy. This disorder is much more common than FSHD, occuring in 1 in 3500 live male births. It is caused by an X-linked recessive mutation, thus explaining why generally only males are affected. The gene encoding dystrophin, a protein essential to proper functioning of the cytoskeletal system, appears to be damaged by a frameshift mutation. This mutation occurs early on in the gene, resulting in complete loss of dystrophin. As a result, signs of this condition usually appear in early childhood, when the child has difficulty walking or lifting oneself up. The legs and arms of the individual are affected. In addition, the muscles of the diaphragm weaken. Breathing becomes difficult, and pulmonary infections are a constant risk. By the early teens, an affected individual may rely completely on a wheelchair, and possibly an assisted breathing device. In some instances, intellectual ability is adversely affected. The individual usually dies in the twenties.
FSHD is usually less severe than Duchenne muscular dystrophy. However, it remains a very debilitating disorder, and for this reason, much research is being done. One research team is utilizing the genes of a myodystrophic mouse, which they feel may serve as a possible animal model for FSHD. They are also trying to see if human candidate genes can match to the mouse genes. In addition, they are sequencing the terminal region of chromosome 4. Another team is conducting a study of 70 FSHD patients. The researchers test the muscle strength of the patients biannually in an attempt to gauge the rate of muscle degeneration. They are also administering a prednisone treatment and noting effectiveness. These research approaches appear creative and promising. As the knowledge of genetics increases, treatments for FSHD and other muscular disorders should improve greatly. These efforts will hopefully lead to an eventual cure.


Cummings, Michael, and Klug, William. Concepts of Genetics, 4th Edition. Prentice Hall, 1994.

Mathews, K.D. Linkage Localization of FSHD in 4q35. American Journal of Human Genetics:51 1992, pp.428-431.

Sarfarazi, Monsoor. Regional Mapping of FSHD Gene on 4q35: Combined Analysis of an International Consortium. American Journal of Human Genetics:51 1992, pp.396-403.

Upadhyaya, Meena. The Mapping of Chromosome 4q Markers in Relation to FSHD. American Journal of Human Genetics:51 1992, pp.404-409.

Weiffenbach, Barbara. Linkage Analysis of Five Chromosome 4 Markers Localizes the FSHD Gene to Distal 4q35. American Journal of Human Genetics:51 1992, pp.416-423.

Wijmenga, C. Genetic Linkage Map of FSHD and Five Polymorphic Loci on Chromosome 4q35-qter. American Journal of Human Genetics:51 1992, pp.411-415.

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