Monday 12 July 2010
Report published on FSHD standards of care and clinical trial readiness
A report has been published on standards of care and clinical trial readiness for facioscapulohumeral muscular dystrophy (FSHD). The report is based on the outcomes of a European Neuromuscular Centre (ENMC) workshop held in the Netherlands in January. Twenty-four expert clinicians and scientists from six European countries, the USA and Australia attended the workshop.
FSHD is the third most common muscle disorder and although no definite cure exists, careful management of the symptoms can lead to significant improvements in quality of life. This workshop brought together patient representatives, clinicians and scientists to define standards of care and discuss what is needed to lay the foundation for future treatments. Recommendations were based on evidence, when available, or on the consensus of expert opinion.
Four main topics were discussed:
Diagnosis
Caring for people with FSHD starts with making the right diagnosis, in the clinic as well as in the laboratory. The symptoms that suggest that a person might have FSHD were discussed as well as alternative diagnoses for clinicians to consider. Patients usually come to the clinic showing signs of weakness in the face, shoulder and abdominal muscles. Hearing and eyesight problems are also common in children with the condition. Once FSHD is suspected a blood test can be taken for genetic diagnosis.
The genetic test for FSHD used in most diagnostic laboratories is highly sensitive and specific. This test detects the deletion of a portion of DNA on chromosome 4 which causes the condition in more than 95% of cases. It is estimated that less than 5% of patients get a false positive or false negative diagnosis from this test. The test is labour and time intensive though, so new techniques are being developed.
There is currently no validated genetic test available for the 3% of patients who do not have the usual DNA deletion on chromosome 4. Genetic diagnosis can only be done on a research basis for these people.
Although prenatal diagnosis is available for FSHD it can take several weeks so the report stated a preference for chorionic villi sampling over amniocentesis.
Pre-implantation genetic diagnosis has its limitations for FSHD so should be approached with caution.
Genetic counselling was discussed, in particular the difficulty in giving accurate information on how the condition will progress for an individual. Often individuals in a family can experience a wide range of symptom severity and often the severity doesn't correlate with the type of genetic fault.
For more information about genetic testing download Target Research magazine.
Clinical management
The clinical management required by people with FSHD can vary greatly. Those with mild symptoms might only need infrequent appointments and minimal treatment but close monitoring and care from a wide range of specialists is required for those whose symptoms started in childhood and are more severe. Below is a brief summary of the recommendations made at the workshop for optimal clinical management of FSHD.
It was recommended that all patients diagnosed with FSHD should have an initial rehabilitation consultation with a physiotherapist and/or occupational therapist. Assessments can be made of balance, walking, posture, and the need for orthoses. Follow-up sessions will depend on the ongoing needs of the patient. Patients with mild disabilities may only need yearly follow-up whereas those with more severe symptoms may need ongoing care from a physiotherapist, orthotist, occupational therapist and a speech pathologist.
Preliminary evidence has shown that exercise can be of benefit for people with FSHD; improving fitness and strength. It is recommended that under the supervision of a health professional, 30 minutes of aerobic exercise (such as cycling or swimming) should be undertaken at least three times per week. If unable to participate in this type of exercise, resistance training with moderate weights can be substituted.
Pain is a common and underestimated complaint in FSHD. There can be multiple causes for this pain and it should be treated with appropriate measures such as physiotherapy and pain medications. Fatigue is also common, which can be addressed by energy conservation strategies and aerobic exercise.
Breathing problems occur in less than 1% of people with FSHD but nonetheless clinicians should be on the lookout for them and treat with non-invasive ventilation when necessary. The benefits of surgery on the shoulder blades (scapular fixation) were discussed and recommendations made. However, there are risks involved and more studies are required to determine when this surgery should be considered.
Pregnancy for women with FSHD is generally considered to be safe with good outcomes but there have been conflicting reports of increased risk of preterm birth and emergency caesarean delivery. Therefore, it was recommended that obstetricians should, as a precaution, treat these pregnancies as high risk and delivery should be in a hospital with appropriate care available.
Hearing should be tested in infants and preschool children diagnosed with FSHD who are at risk of hearing loss because undiagnosed hearing problems can delay their development. All patients with FSHD should be referred to an ophthalmologist to check for an eye condition known as "retinal vasculopathy". This is a relatively common problem but rarely causes symptoms. If necessary the eyes can be easily treated with lasers.
Clinical trial readiness
It is critical that the components needed to efficiently conduct clinical trials in FSHD patients are in place in time for any potential treatments that may come along in the near future.
Firstly, so called "outcome measures" need to be in place. These are ways to accurately measure if a new treatment is effective. Manual methods for measuring muscle strength and tests which involve timing how long it takes a person to perform an activity such as walking, have been established as reliable for FSHD. Measuring the size of muscles using scans such as ultrasound, DEXA or MRI have also been investigated but it is still not clear if a change in muscle size is a good reflection of symptom progression.
The regulatory authorities such as EMEA now favour patient reported outcome measures such as quality of life questionnaires to measure what impact a treatment has on a person's daily life. Ideally a questionnaire needs to be designed specifically to measure the unique issues and symptoms relevant to people with FSHD.
Being able recruit patients interested in participating in clinical trials has been a significant obstacle for clinical trials for other conditions in the past. The establishment of patient registries is therefore essential for clinical trial readiness. Currently there are large registries in the USA and Italy as well as other smaller informal FSHD registries in other countries. FSHD Europe is planning to develop a European registry. It was agreed that developing a global registry using the model set up by TREAT-NMD to combine data from existing registries would help to facilitate future clinical trials for FSHD. This would require agreement on a core amount of data that needs to be present in all the registries to allow them to be combined.
The Future
The workshop participants identified key issues that need to be addressed to improve standards of care for FSHD:
- Development of best practice guidelines for genetic testing.
- A more comprehensive assessment of pain, pregnancy and surgical interventions for FSHD.
Working groups were formed to address the following:
- The development of outcome measures such as quality of life questionnaires.
- The core data to be stored in patient registries so that a global registry can be developed.
The workshop attendees agreed to meet in approximately one year to re-examine outstanding issues.
Further information and links
More information about FSHD.
The European Neuromuscular Centre (ENMC) is an international research support organization funded and steered by neuromuscular patient organisations, including the Muscular Dystrophy Campaign. The ENMC strives to facilitate communication amongst scientists and clinicians by funding and organising between eight and 10 interactive workshops each year. More information about the European Neuromuscular Centre.
Read about the FSHD research we fund:
The report was published in the journal Neuromuscular Disorders and is only available after payment of a fee. The reference for the paper is:
Tawil R, van der Maarel S, Padberg GW, van Engelen BG. 171st ENMC International Workshop: Standards of care and management of facioscapulohumeral muscular dystrophy. Neuromuscul Disord. 2010 Jul;20(7):471-5.
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