Facioscapulohumeral Muscular Dystrophy, abbreviated either as FSH or FSHD, is an inherited disorder of muscle that causes progressive deterioration of muscle fibers resulting in muscle atrophy and weakness. It is one of many different forms of muscular dystrophy, each with a different genetic cause as well as different clinical symptoms, severity, and rate of progression. FSHD is the third most common form of muscular dystrophy after Duchenne muscular dystrophy and myotonic dystrophy.
This condition gets its name from the muscles that are affected most often: those of the face (facio-), around the shoulder blades (scapulo-), and in the upper arms (humeral). The signs and symptoms of facioscapulohumeral muscular dystrophy usually appear in adolescence. However, the onset and severity of the condition vary widely. Milder cases may not become noticeable until later in life, whereas rare severe cases become apparent in infancy or early childhood. FSHD is a disease that usually progresses very slowly and rarely affects the heart or respiratory system, hence it isn’t considered life-threatening. Most people with the disease have a normal lifespan.
Symptoms may manifest early, sometimes years before a formal diagnosis. These can (but don’t always) include:
- Inability to whistle
- Inability to sip through a straw
- Eyes that don’t close fully during sleep
- Difficulty with such exercises as sit-ups and pull-ups
- Shoulder blades that “wing” out
- Difficulty raising arm above shoulder height
- Foot drop (foot dorsiflexion weakness)
- Weak lower abdominal muscles, protuberant abdomen
- Curved spine (lordosis).
Patients can also experience:
- Episodes of “malaise” or “burning pain” in muscles
- Severe pain from changes in posture and strain on remaining muscles
- Chronic fatigue
- Respiratory insufficiency
- Hearing loss
- Coats’ disease (retinal telangiectasis); rare
FSHD is usually inherited as an autosomal dominant trait, where a single copy of the disease gene, from either parent, will be expressed ‘dominating’ the other normal gene, resulting in the appearance of the disease. The risk of transmitting the disorder from affected parent to offspring is 50 percent for each pregnancy regardless of the sex of the child. In about 10 to 30 percent of individuals with FSHD, there is no apparent family history and genetic mutations are thought to occur spontaneously with no known cause.
There are two main types of FSHD. FSHD1 affects 95% of patients and FSHD2 affects the remaining 5% of patients. In both cases, the genetic DNA code affected, lies on chromosome 4 and is referred to as the D4Z4 region. The D4Z4 region can be considered as a control center on chromosome 4 and is responsible for suppressing the genes local to it. In FSHD, the D4Z4 area doesn’t function properly and results in the increased activity of genes that would normally be silent. The decreased activity in the D4Z4 area can be because it is shorter than normal (FSHD1) or there being a lack of activity in another gene (SMCHD1) that would normally activate D4Z4 (FSHD2). In both cases, with the D4Z4 area being underactive, there is subsequent over activity of a neighboring gene called DUX4. It is the increased activity in the DUX4 gene that is thought to result in damage to the muscle cells resulting in muscle wasting and weakness.
FSHD is worldwide in distribution, is equally prevalent in both sexes and has no particular racial, geographic or ethnic distribution. Therefore, FSHD can appear in any family and happen at any time. Males are typically more severely affected than females, and there is a wide clinical inter- and intra-familial variability of the disease, with approximately 20% of patients eventually becoming wheelchair-bound and with an equal frequency of non-penetrant gene carriers. FSHD has a prevalence of 1 in 20,000.
FSH is primarily diagnosed based on the clinical evaluation, including the presence of muscle weakness in the pattern described above with an appropriate age of onset and a family history indicating an autosomal dominant inheritance. In addition, the following laboratory findings are supportive of the diagnosis:
- Serum CPK – normal to mildly elevated (no more than 10 times normal)
- Electromyography (EMG) – myopathic pattern with short muscle unit action potential duration and an increased recruitment pattern.
- Electrocardiogram (ECG) – normal, unless there is coexistent cardiac disease
- Muscle Biopsy – reveals isolated angular fibers, some necrotic fibers, and moderate endomysial connective tissue proliferation. These findings are multifocal, with some areas of the muscle appearing normal and others appearing severely affected. There may also be inflammatory cells seen.
- Genetic Testing – DNA analysis for the chromosome 4q35 deletion, however, this is positive in only 77% of FSH patients and is also positive in 21% of normal controls.
In order to confirm the diagnosis of FSH it is also necessary to exclude those disorders which may look like FSH by a process of elimination.
There are no known treatments that will reverse the muscle weakness and waste in FSHD. Treatment is symptomatic, aiming towards prevention of joint stiffness and pain by passive mobilization and administration of antalgics. In severe cases, ventilatory support may be required. Surgical treatment involves fixation of the scapula and may lead to an improvement in the range of motion of the arms. Physical therapy is critical in maintaining joint mobility, stretching and strengthening muscles and in preventing and improving chronic pain.
- Facioscapulohumeral Muscular Dystrophy (FSH, FSHD). MDA – Muscular Dystrophy Association. www.mda.org/disease/facioscapulohumeral-muscular-dystrophy. Retrieved on 10-04-2017.
- General Information about FSHD. University of Rochester Medical Center – The Richard Fields Center for FSHD Research. www.urmc.rochester.edu/fields-center/patients.aspx Retrieved on 10-04-2017.
- Facts and Statistics about FSHD. UMMS Wellstone Center for FSHD. www.umassmed.edu/wellstone/aboutfshd/fshdfacts/. Retrieved on 10-04-2017.
- Facioscapulohumeral Muscular Dystrophy. Yale School Of Medicine. www.medicine.yale.edu/neurology/patients/neuromuscular/fmd.aspx. Retrieved on 10-04-2017.
- Facioscapulohumeral muscular dystrophy (FSHD). FacialPalsy UK. www.facialpalsy.org.uk/causesanddiagnoses/facioscapulohumeral-muscular-dystrophy-fshd/ Retrieved on 10-04-2017.
- Facioscapulohumeral dystrophy. Orphanet. www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=269 Retrieved on 10-04-2017.
- Facioscapulohumeral Muscular Dystrophy. AANEM – American Academy of Neurology. www.muscle.ca/wp-content/uploads/2012/11/FSHD-Family-Guidelines-AAN-2015.pdf Retrieved on 10-04-2017.
- Facioscapulohumeral Muscular Dystrophy. Genetics Home Reference. www.ghr.nlm.nih.gov/condition/facioscapulohumeral-muscular-dystrophy. Retrieved on 10-04-2017.
- Symptoms of facioscapulohumeral muscular dystrophy. FSH Society. www.fshsociety.org/facioscapulohumeral-description/. Retrieved on 10-04-2017.
- Facioscapulohumeral Muscular Dystrophy. NORD – National Organization for Rare Disorders. www.rarediseases.org/rare-diseases/facioscapulohumeral-muscular-dystrophy/ Retrieved on 10-04-2017.
- Facts about Facioscapulohumeral Muscular Dystrophy. Muscular Dystrophy Association Australia. www.mdaustralia.org.au/wp-content/uploads/2012/07/004_facioscapulohumeral-md-july-2012.pdf Retrieved on 10-04-2017.