What is Facioscapulohumeral Muscular Dystrophy, FSHD or FSH Disease?
Facioscapulohumeral muscular dystrophy or FSHD is the most prevalent of the nine primary types of muscular dystrophy affecting adults and children. Muscular dystrophy in general connotes a genetic, hereditary muscle disease that causes progressive muscle weakness. FSHD is also broadly characterized as a neuromuscular disease (NMD), as muscular dystrophy is a subset of NMD. Muscular dystrophies are alike in that they cause progressive skeletal muscle weakness, defects in the biochemical, physical and structural components of muscle, and the death of muscle cells and tissue. However, researchers believe that the causes of each of the muscular dystrophies are not necessarily the same.
The major symptom of FSHD is the progressive weakening and loss of skeletal muscles. The usual location of these weaknesses at onset is the origin of the name: face (facio), shoulder girdle (scapulo) and upper arms (humeral). Early weaknesses of the muscles of the eye (open and close) and mouth (smile, pucker, whistle) are distinctive for FSHD. These symptoms, in combination with weaknesses in the muscles that stabilize the scapulae (shoulder blades), are often the basis of the physician’s diagnosis of FSHD.
In most cases, FSHD muscle involvement starts in the face and slowly progresses to the shoulder and upper arm muscles and then down to the abdominal and foot extensor muscles. Foot drop and foot weakness are early manifestations. Initial signs of FSHD include difficulty reaching above the shoulder level, foot drop, scapular winging and facial weakness. Weakness in the abdominal muscles can cause a protuberant abdomen and lumbar lordosis. The lower abdominal muscles are usually weaker than the upper abdominal muscles. This distribution of weakness is not seen in many other diseases and, therefore, is very specific to FSHD.
Although the progression of FSHD is quite variable, it is usually relatively slow. With FSHD, most affected people develop unbalanced (side-to-side) weaknesses. The reason for this asymmetry is unknown.
In more than half of FSHD cases, there are other symptoms including high-frequency hearing loss and/or abnormalities of blood vessels in the back of the eye. The vascular abnormalities in the back of the eye lead to vision problems in only about 1% of the cases. Since these abnormalities are not exclusive to FSHD, one must bear in mind that their presence alone, in an FSHD at-risk individual, is insufficient for a diagnosis of FSHD.
Although not typical, some patients with FSHD have respiratory insufficiency, especially those with severe FSHD.
FSHD generally presents outward signs in 95% of affected individuals by the second decade of life for men and the third decade of life for women. The disease is said to have a penetrance of 95% in men by the second decade and in women by the third decade.
FSHD is worldwide in distribution, affects both sexes equally and has no particular racial, geographic or ethnic distribution. Therefore, FSHD can appear in any family and happen at any time.
Types of FSHD
FSHD has been classified into two types: FSHD1A and FSHD1B. The symptoms are the same; the difference between the types is in their genetic locus.
Facioscapulohumeral muscular dystrophy 1A (FSHD1A), also known as chromosome 4 linked facioscapulohumeral muscular dystrophy, is by far the most common. FSHD1A is associated by genetic testing with the deletion of 3.3-kb repeats from a chromosomal tandem repeat called D4Z4 located near the end of chromosome 4 at the 4q35-qter location. The D4Z4 region is a polymorphic variable number tandem repeat (VNTR) array consisting of 3.3 kb units. Unaffected individuals have a chromosome 4 D4Z4 array that has a span of 11 to 150 contiguous units. In individuals with FSHD1A, the chromosome 4 D4Z4 repeat array is contracted to a range between 1 to 10 contiguous units. There is a rough and inverse relationship between clinical severity and the number of repeats; patients with the fewest repeats typically have the most severe symptoms.
Facioscapulohumeral muscular dystrophy 1B (FSHD1B), also known as non-chromosome 4 linked facioscapulohumeral muscular dystrophy, is much less prevalent than FSHD1A. It may be caused by different genes from FSHD1A, located on the same (despite its title) or different chromosomes.
Infantile FSHD or IFSHD is a more severe form of FSHD1A and FSHD1B that has recently been categorized as a subtype of FSHD1A and FSHD1B. What makes the disease more severe has not yet been determined. Hearing loss (high frequency bilateral sensorineural), vision problems (Coats’ Disease and retinal telangiectasias), and seizures have been documented in IFSHD. Hearing loss is often more severe in IFSHD; if not detected and treated early it can interfere with learning and cognitive development.
Incidence of FSHD
The most common form of FSHD by far is FSHD type 1A (chromosome 4-linked FSHD). A conservative estimate of incidence is 1 in 14,000 births throughout the world; however, due to increased experience with FSHD, population-based research and improved genetic testing, this estimate may be low; actual incidence may be 1 in 7,500.
FSHD type 1B (non-chromosome 4-linked FSHD) is much rarer than FSHD type 1A (chromosome 4-linked FSHD). There is no generally accepted estimate of its incidence, but incidence is unlikely to exceed 2% of all cases of FSHD.
Infantile FSHD (IFSHD) is characterized by onset in early childhood. There is no generally accepted estimate of its incidence, but it is rare.
Other Medical Terms
Landouzy-Dejerine Muscular Dystrophy - The older name for FSHD; named after Landouzy and Dejerine, who first described the disease in 1885.
Genetics of FSHD
Both types of FSHD are autosomal dominant genetic disorders. Each child of a parent with FSHD has a 50% chance of inheriting FSHD. The type of FSHD inherited by the child is always the same as that of the affected parent (i.e. if the parent has FSHD1A, each child is at 50% risk for FSHD1A). The severity of the symptoms may differ from person to person within a family.
Sporadic FSHD cases result from a new mutation. Studies report from 10% to as high as 33% of FSHD cases as sporadic (de novo mutation). Approximately 20% of reported sporadic cases are those inherited from a seemingly unaffected parent who is a “germline mosaic,” meaning that only the mother’s or father’s germ cells (the egg or sperm) is affected. When a germline mosaic is involved, the parent appears unaffected but the children are at risk. In the remaining 80% of sporadic cases, neither parent's genes are affected; a new spontaneous mutation results in a chromosome 4 deletion that causes FSHD1A. When the 4q35 deletion fragment appears in a sporadic FSHD case, it is transmitted in an autosomal dominant (only one parent needs to be affected) manner to succeeding generations. The probability, then, of passing the disease to an offspring is 50%.
Genetic counselors help individuals, families and couples affected by or at risk for FSHD to work through the process of genetic testing for the disease. Genetic counseling also helps individuals, families and couples as they plan to have a baby. Prenatal and in-vitro fertilization pre-implantation genetic (PGD IVF) tests are available for FSHD1A (chromosome 4 linked FSHD). Genetic counselors help couples consider possible scenarios and alternatives, such as having a child with FSHD, adoption or artificial insemination. In this way, couples arrive at a decision that is right for them.
FSH Society, Inc. • 450 Bedford Street • Lexington, MA 02420 • Tel: 781 301-6060 • Fax: 781 862-1116