What is FSHD?
Facioscapulohumeral Dystrophy (FSHD) is an inheritable muscle disease, characterised by the progressive weakening and loss of skeletal muscles. There is no known cure or treatment for FSHD.
A 2010 report by Orphanet entitled ‘Prevalence of rare diseases: A bibliographic study’ estimates that FSHD affects 7 in 100,000 people, making it one of the most prevalent forms of muscular dystrophy. Yet there has been no focused research or funding for FSHD research in Australia and minimal funding overseas. Research into FSHD is twenty years behind that of research into other forms of Muscular Dystrophy.
At onset, the usual location of these weaknesses is in the face (facio), shoulders (scapulo) and upper arms (humeral). Early weaknesses in the muscles of the eye (to open and close) and mouth (smile, pucker, whistle) are also distinctive for FSHD. It is common for a combination of these symptoms to be the basis of a doctor’s diagnosis of FSHD in a patient.
The progression of FSHD is quite variable, yet tends to be slow. In the majority of cases, FSHD muscle involvement starts in the face and slowly progresses to the shoulder and upper-arm muscles, then moving down to the abdominal and foot-extensor muscles.
Muscle weakness in FSHD can present asymmetrically meaning that weakness can differ between the left and right side of the body. Sometimes this difference in weakness can be quite striking. The reason for this asymmetry is unknown and is a unique characteristic to FSHD as compared to other dystrophies.
Initial signs of FSHD include foot drop, scapular winging and difficulty reaching above the shoulder level due to the progressive weakness in the muscles that stabilise the scapulae (shoulder blades). Some sufferers may lose the ability to show any facial expressions and experience serious speech impediments due to the weakening of facial muscles.
In more than 50 per cent of cases there are other symptoms including high-frequency hearing loss and/or abnormalities of blood vessels in the back of the eye, which lead to visual problems in approximately 1% of cases. Most patients can have these changes in the blood vessels but experience no visual problems. These eye and hearing symptoms are not in themselves a sufficient diagnosis for FSHD.
The Causes of FSHD
FSHD is caused by a sudden structural change, or mutation, in DNA. While the gene(s) causing the disease is yet to be identified, its location is approximated to be toward the end of the DNA of the long arm of chromosome 4. The specific genetic location of the FSHD deletion is 4q35 in the D4Z4 DNA region.
The size of the FSHD deletion has a relationship with the severity of the disease – patients with the fewest repeats (the largest deletion) typically have the most severe symptoms. It is not yet certain whether the deleted DNA contains an active gene or changes the regulation or activity of a nearby FSHD gene.
Most individuals with FSHD inherit the mutation from a parent with the disease, although up to one-third of cases appear to be sporadic, the result of a new mutation.
Inheriting FSHD
FSHD is inherited as an autosomal dominant disease. DNA is the means of transmission of inheritable traits from parent to child and chromosomes are the vehicles for these DNA transfers from one generation to the next.
Only one parent has to have the disease gene or deletion for his or her child to inherit FSHD and the son or daughter of an affected person is at 50% risk of inheriting the defective gene.
Sporadic cases of FSHD
Sporadic cases of FSHD are those resulting 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. In the remaining 80% of cases neither parent’s genes are affected – a spontaneous mutation has resulted in a chromosome 4 deletion, causing FSHD. When this occurs in a sporadic case, the 4q35 deletion fragment transmitted in an autosomal dominant manner to succeeding generations.
Incidence
FSHD occurs with equal frequency in both males and females and can affect children and adults of all ages and all racial groups. According to Orphanet, the estimated incidence of FSHD in the general population is 7 in 100,000, yet it is difficult to calculate the exact incidence of FSHD due to misdiagnosis and lack of understanding and awareness of the disease. Thus the incidence may be under reported.
Current estimates have recently reported that 1 in 7,500 people are affected. No appropriate research has been conducted to determine true estimates within the Australian population.
The most common form of FSHD is FSHD type 1A (chromosome 4-linked FSHD). FSHD type 1B (non-chromosome 4-linked FSHD) is a much rarer form, with its incidence unlikely to exceed 2% of all cases of FSHD.
Infantile FSHD, which is characterised by early childhood onset, is also rare.
Appearance of Symptoms
The onset of FSHD is variable. Symptoms may develop in early childhood and are usually noticeable in the teenage years with 95% of affected individuals manifesting the disease by age 20.
In 5%-10% of FSHD cases a young child or an infant can develop symptoms in their first two years of life and these symptoms are usually more severe than symptoms seen in patients with later onset. Infantile FSHD can present earlier facial weakness during the first two years of life, as well as the other typical muscle weaknesses of FSHD. Some of these children also experience early hearing losses and retinal abnormalities.
More research is needed to address the understanding of these abnormalities seen in FSHD.
Predicting the Course and Outcome of FSHD
The degree of severity and symptoms for FSHD patients can vary greatly ranging from asymptomatic individuals with minimal symptoms to patients who are wheelchair bound. There have been cases where some people with FSHD do not even know that they have it.
There are aspects of FSHD that are both certain and uncertain.
There is certainty that some muscles will become weak and waste away throughout life. This will indirectly affect the person’s social, personal and occupational activities as they age. FSHD does not affect the person’s intellect and as a group, FSHD people are well adjusted, motivated and educated.
On average those with FSHD have a normal life span yet there have been some cases where it has reduced the person’s life span due to secondary complications that have arisen from the primary muscle wastage. More research is needed to monitor patient risk.
The uncertainties of FSHD are that the rapidity and extent of muscle loss differ considerably among FSHD patients. The difference can also be seen within same family members who have the same genetic deletion defect. Some patients find that they have few difficulties throughout life while many may eventually find walking too difficult or impossible and may have to use or be confined to a wheelchair.
While there is a basic understanding of FSHD, there is still much information that is unknown. The most disturbing news for a person who has been diagnosed with FSHD is that the pathophysiology of FSHD is still unknown.
The most disturbing news for a person who has been diagnosed with FSHD is that while there is a basic understanding of FSHD there is much information, including the pathophysiology, that remains unknown.
Diagnosis of FSHD
A doctor who is familiar with the disease will be able to perform a dependable diagnosis of FSHD when there are symptoms that follow an expected pattern and location of weakening muscles. A thorough examination will detect the disease in approximately 95 per cent of affected individuals aged 20 or older.
There is a DNA test for FSHD which is highly reliable. The test detects the 4q35 DNA deletion, and is approximately 98 per cent reliable as a presumptive diagnosis of FSHD.
Prenatal testing is also available, following the same DNA procedure.
Treatments and Aids for FSHD
There is currently no cure or treatment for FSHD. However, there are certain steps that suffers can take to lessen the physical effects.
Those with FSHD should try to remain as physically active as possible. Physical therapy and light exercise, especially swimming, can help to maintain flexibility, often making many movements easier.
Maintaining a good healthy is also important. Unnecessary weight should be avoided, so as not to cause any unwarranted stress on already weakened muscles.
There are a number of different professionals who can be of some help to FSHD patients, including neurologists, occupational therapists, dieticians and speech and hearing therapists.