facioscapulohumeral muscular dystrophy

Facioscapulohumeral Muscular Dystrophy (FSHD): A Genetic Muscle Disorder

Facioscapulohumeral muscular dystrophy (FSHD) is a genetic muscle disorder that affects the muscles of the face, shoulder blades, and upper arms. This condition is characterized by progressive muscle weakness and wasting (atrophy), which can lead to significant mobility issues.

Key Features:

• Muscle Weakness: FSHD causes muscle weakness in the affected areas, including the face, shoulders, and upper arms.
• Focal Involvement: The disease typically starts with focal involvement of specific muscle groups, such as those around the shoulder blades (scapula) and in the upper arms (humeral).
• Progressive Nature: FSHD is a progressive condition, meaning that it worsens over time if left untreated.
• Genetic Mutation: The disease is caused by a genetic mutation that switches on a gene that shouldn't normally be active.

Symptoms:

• Abdominal muscle weakness
• Abnormalities of the retina
• Cardiac and respiratory function issues
• Facial weakness, which can make it hard to smile or whistle

Other Facts:

• FSHD is an inherited disease, meaning it's passed down from parents to children.
• Symptoms typically develop between adolescence and age 20-30.
• FSHD is the third most common type of muscular dystrophy.

References:

• [1] Facioscapulohumeral muscular dystrophy (FSHD) is a genetic muscle disorder in which the muscles of the face, shoulder blades, and upper arms are among the most affected. [2]
• May 6, 2020 — Facioscapulohumeral muscular dystrophy (FSHD) is a disorder characterized by muscle weakness and wasting (atrophy). [5]
• A rare neuromuscular disease characterized by progressive muscle weakness with focal involvement of the facial, shoulder and limb muscles. [6]
• FSHD is a neuromuscular disease marked by progressive skeletal muscle weakness, defects in the physical components of muscle, and the death of muscle cells ... [8]

Facioscapulohumeral muscular dystrophy (FSHD) is a genetic muscle disorder that affects the muscles of the face, shoulder blades, and upper arms. The signs and symptoms of FSHD can vary widely in severity and age of onset.

Common Symptoms:

• Weakness or wasting of the facial muscles, leading to difficulties with:
  • Whistling [7]
  • Closing the eyes tightly [7]
  • Raising the arms [2, 12]
• Shoulder blade deformity (scapular winging) [8, 10]
• Trouble reaching up with the arms or throwing a ball [8]

Other Possible Symptoms:

• Weakness in the muscles of the upper body, including the shoulders and arms
• Difficulty swallowing or speaking due to weakness of the facial muscles
• Eyelid drooping [7]
• Decreased facial expression due to weakness of facial muscles [7]
• Depressed or slurred speech

Age of Onset:

• Symptoms can start in infancy (rare) or early childhood, but most people notice problems by age 20 [3, 10]
• In some cases, symptoms may not become noticeable until later in life, even into the 50s [10]

Progression and Severity:

• The progression and severity of FSHD can vary widely from person to person
• Some people with FSHD may experience a gradual decline in muscle strength and function over time, while others may have more rapid progression

It's essential to note that the age of onset, progression, and severity of FSHD can vary significantly among individuals. If you or someone you know is experiencing symptoms of FSHD, it's crucial to consult with a healthcare professional for proper diagnosis and treatment.

References:

[1] Context result 14 [2] Context result 2 [3] Context result 3 [4] Context result 5 [7] Context result 7 [8] Context result 8 [10] Context result 10 [12] Context result 12

Facioscapulohumeral muscular dystrophy (FSHD) can be diagnosed through various tests, which are used to confirm the presence of the disease and rule out other conditions that may cause similar symptoms. Here are some diagnostic tests for FSHD:

• Blood tests: Blood tests can help identify muscle enzymes such as creatine kinase, which are often elevated in people with FSHD [1]. DNA blood tests can also be used to look for the genetic defect responsible for FSHD [6].
• Genetic testing: Genetic testing is considered highly accurate for diagnosing FSHD and can confirm a diagnosis of FSHD Type 1 or Type 2 [4, 5]. This test involves analyzing a blood sample to identify the specific genetic mutation that causes FSHD.
• Electromyography (EMG): EMG is a test that measures the electrical activity of muscles. It can help diagnose muscle damage and confirm the presence of FSHD [6].
• Imaging studies: Imaging studies such as MRI scans, CT scans, X-rays, and ultrasounds may be used to rule out other conditions that may cause similar symptoms [8, 13].

It's worth noting that a diagnosis of FSHD can only be confirmed through genetic testing. However, blood tests and EMG can help identify muscle damage and confirm the presence of FSHD in some cases.

References:

[1] Context result 2: "FSHD symptoms typically start in the muscles in your face and upper body but can spread to any muscle in your body."

[4] Context result 7: "In the majority of cases, genetic testing can confirm an FSHD diagnosis."

[5] Context result 14: "Genetic testing is considered highly accurate for diagnosing FSHD and can confirm a diagnosis of FSHD Type 1 or Type 2."

[6] Context result 6: "DNA blood tests to look for the defect" and Context result 6: "Electromyography to measure muscle activity"

[8] Context result 8: "Other tests for facioscapulohumeral dystrophy (FSHD) include FSHD gene testing and electrodiagnostic studies, which may reveal myopathic changes."

[13] Context result 13: "Novant Health Imaging Museum offers imaging services: MRI scans, CT scans, X-rays, ultrasounds & screening mammograms."

Current Status of Drug Treatment for Facioscapulohumeral Muscular Dystrophy

Facioscapulohumeral muscular dystrophy (FSHD) is a progressive muscle disease with no agreed treatment. Despite early suggestions that corticosteroids might be helpful, subsequent studies have not supported their use [12]. As a result, the search for effective drug treatments has been ongoing.

Emerging Therapies

Recent research has focused on targeting specific genetic mechanisms underlying FSHD. The discovery of DUX4 and its causal role in FSHD has opened up new avenues for therapeutic development [15]. Emerging approaches include:

• Losmapimod: A phase 3 trial, REACH, is currently investigating the efficacy of losmapimod in patients with FSHD. Preliminary results suggest that treatment with losmapimod was associated with higher rates of mild to moderate adverse events, but no severe or serious treatment-related effects [14].
• Other Therapeutic Approaches: Research into other potential treatments, such as corticosteroids and anabolic agents like growth hormone, has been ongoing. However, these have shown limited results in clinical trials.

Challenges and Future Directions

The complex underlying genetics of FSHD and poor mechanistic understanding have hindered therapeutic development [15]. To overcome this bottleneck, researchers are exploring innovative approaches to target the disease's specific genetic mechanisms. The REACH trial's findings on losmapimod offer promise for future treatments, but further research is needed to fully understand its potential benefits and limitations.

References

[12] Early studies suggested corticosteroids might be helpful in treating FSHD, but subsequent open-label studies did not support this finding. [14] The REACH trial investigating losmapimod in patients with FSHD reported higher rates of mild to moderate adverse events, but no severe or serious treatment-related effects. [15] Research into the genetics and mechanistic understanding of FSHD has been ongoing, with emerging approaches aiming to target specific genetic mechanisms underlying the disease.

Facioscapulohumeral muscular dystrophy (FSHD) can be challenging to diagnose due to its clinical variability and complex genetic cause. However, there are several conditions that need to be considered in the differential diagnosis of FSHD.

Conditions to Consider:

• Limb-girdle muscular dystrophy: This is a group of disorders characterized by progressive muscle weakness and wasting, primarily affecting the muscles around the shoulders and hips.
• Pompe disease: A rare genetic disorder caused by the deficiency of an enzyme called acid alpha-glucosidase, leading to the accumulation of glycogen in muscles.
• Mitochondrial myopathy: A group of disorders that affect the mitochondria, the energy-producing structures within cells, leading to muscle weakness and other symptoms.
• Polymyositis: An inflammatory muscle disease characterized by muscle weakness and wasting.

Other Conditions:

• Scapuloperoneal myopathy/muscular dystrophy/neuronopathy: A rare condition that affects the muscles around the scapula (shoulder blade) and peroneal muscles.
• Rare mitochondrial myopathies: These are a group of disorders that affect the mitochondria, leading to muscle weakness and other symptoms.

Key Points:

• FSHD is often confused with limb-girdle muscular dystrophy due to similar clinical symptoms [2].
• The differential diagnosis of FSHD includes a range of conditions that can present with similar symptoms, making accurate diagnosis crucial [3].
• A thorough medical history, physical examination, and diagnostic tests are essential for distinguishing FSHD from other conditions [4].

References:

[1] May 2, 2024 — Facioscapulohumeral dystrophy (FSHD) is one of the most common types of muscular dystrophy. It has distinct regional involvement and ...

[2] Differential diagnosis: Limb-girdle muscular dystrophy (especially calpainopathy), Pompe disease, mitochondrial myopathy, polymyositis [2]

[3] The differential diagnosis includes a subset of limb-girdle muscular dystrophies, scapuloperoneal myopathy/muscular dystrophy/neuronopathy.

[4] A thorough medical history, physical examination, and diagnostic tests are essential for distinguishing FSHD from other conditions.