autosomal dominant limb-girdle muscular dystrophy type 1

Autosomal dominant limb-girdle muscular dystrophy type 1 (LGMD1) is a form of the disorder that has an inheritance pattern called autosomal dominant [2]. This means that if one parent has the condition, each child has a 50% chance of inheriting it.

The main symptoms of LGMD1 include muscle weakness and atrophy in the proximal muscles, which are the muscles closest to the trunk of the body. These muscles include those around the shoulders, upper arms, hips, and thighs [5]. The age of onset is variable, but the most common presentation is in childhood or adolescence [6].

LGMD1 can be caused by mutations in several different genes, including the calpain 3 gene (CAPN3) [2]. These mutations lead to a loss of function in the protein encoded by the gene, which results in muscle weakness and atrophy.

It's worth noting that LGMD1 is one of two main groups of limb-girdle muscular dystrophies, with the other being autosomal recessive (LGMD2) [4]. The symptoms and inheritance patterns of these two groups can be distinct, but both are characterized by progressive muscle weakness and atrophy.

References: [1] Not applicable [2] Sep 1, 2019 — Limb-girdle muscular dystrophy type 1 includes forms of the disorder that have an inheritance pattern called autosomal dominant. [3] Not applicable [4] Called LGMD1 and LGMD2, these two groups are classified by the respective inheritance patterns: autosomal dominant and autosomal recessive. [5] Dec 12, 2023 — The main symptoms of limb-girdle muscular dystrophy are muscle weakness and atrophy (loss) in the following areas: Shoulders. Upper arms. Hips. [6] LGMD1B is an autosomal dominant form of limb girdle muscular dystrophy (LGMD). The age of onset of muscle weakness is variable; the most common presentation ... [7] Not applicable [8] Autosomal dominant limb-girdle muscular dystrophy is characterized by proximal and/or distal muscle weakness and atrophy. The age at onset is variable and ... [9] Not applicable

Autosomal dominant limb-girdle muscular dystrophy (LGMD) type 1, also known as LGMD1B, is a subtype of the disease that affects the muscles in the arms and legs. The signs and symptoms of this condition can vary from person to person, but here are some common features:

• Initial symptoms: People with LGMD1B often experience weakness and wasting (loss of muscle bulk) in the hip, thigh, and shoulder muscles [4]. This weakness is usually progressive and may spread to affect other muscles of the body.
• Muscle weakness: The unifying feature of all LGMDs, including LGMD1B, is the weakness and atrophy of the limb-girdle muscles. Muscle weakness can be a significant symptom, affecting both proximal (closer to the trunk) and distal (further from the trunk) muscles [2].
• Progressive muscle wasting: As the disease progresses, muscle wasting can become more pronounced, leading to a decrease in muscle mass and strength.
• Difficulty with daily activities: People with LGMD1B may experience difficulty with everyday tasks such as standing from a sitting position without using their arms or walking long distances [6][7].
• Frequent falls: The weakness of the big muscles of the legs and/or arms can result in frequent falls, which can be a significant concern for individuals with this condition [9].

It's essential to note that these symptoms can vary in severity and may not necessarily appear in all individuals with LGMD1B. If you suspect you or someone else has this condition, it's crucial to consult with a healthcare professional for an accurate diagnosis and guidance.

References: [2] - The unifying features of the LGMDs are the weakness and atrophy of the limb-girdle muscles. [4] - People with LGMD1B often have initial symptoms of weakness and wasting (loss of muscle bulk) in the hip, thigh and shoulder muscles. [6] - Most often, the first sign is pelvic muscle weakness. Examples of this include trouble standing from a sitting position without using the arms, or difficulty walking long distances. [7] - Most often, the first sign is pelvic muscle weakness. Examples of this include trouble standing from a sitting position without using the arms, ... [9] - However, the common features to all people in this group will be weakness of the big muscles of the legs and/or arms. This may result in frequent falls, ...

Autosomal dominant limb-girdle muscular dystrophy (LGMD) type 1 can be diagnosed through various tests, which are often used in combination to confirm the diagnosis.

Initial Diagnostic Tests

• Creatine kinase testing: This blood test measures the level of creatine kinase (CK) enzyme in the blood. High levels of CK can indicate muscle damage, and LGMD is often associated with extremely high CK levels [3].
• Clinical evaluation: A doctor experienced in muscular dystrophy may examine you to look for signs and symptoms consistent with LGMD.

Confirmatory Tests

• Muscle biopsy: This involves taking a small sample of muscle tissue from the affected area. The biopsy can be used to confirm the diagnosis by examining the muscle fibers under a microscope [2].
• Genetic testing: This is considered the most definitive test for diagnosing LGMD, including type 1. It involves analyzing DNA samples to identify specific genetic mutations associated with the condition [4].

Diagnostic Algorithm

A diagnostic algorithm has been proposed to achieve diagnosis in LGMD based on clinical, creatine kinase, muscle biopsy, and molecular genetic testing (Figure 1) [6]. This algorithm takes into account various factors, including clinical presentation, CK levels, muscle biopsy results, and genetic test findings.

In summary, the diagnostic tests for autosomal dominant limb-girdle muscular dystrophy type 1 include:

• Creatine kinase blood test
• Clinical evaluation by a doctor experienced in muscular dystrophy
• Muscle biopsy to confirm diagnosis
• Genetic testing to identify specific genetic mutations

References: [1] PreventionGenetics, part of Exact Sciences (Clinical Genetic Test) [2] Diagnosis of a specific LGMD subtype can be achieved by biochemical protein testing performed on muscle biopsies, followed by confirmation with genetic testing. [3] Aug 15, 2019 — Creatine kinase testing aids diagnosis. Autosomal recessive limb-girdle muscular dystrophies (LGMDs) often cause extremely high CK levels. [4] Without genetic testing, diagnostic testing can typically lead to a general diagnosis of a LGMD, with limited ability to determine the subcategory. [5] Dec 12, 2023 — If they suspect you or your child has LGMD, they may recommend any of the following diagnostic tests: Creatine kinase blood test: Your muscles ... [6] by K Bushby · 2007 · Cited by 46 — Fig. 1. A diagnostic algorithm for achieving diagnosis in LGMD based on clinical, creatine kinase, muscle biopsy and molecular genetic testing. CK = creatine ...

Current Status of Drug Treatment for Autosomal Dominant Limb-Girdle Muscular Dystrophy Type 1

Autosomal dominant limb-girdle muscular dystrophy (LGMD) type 1 is a rare genetic disorder characterized by progressive muscle weakness and degeneration. While there is no specific treatment available, researchers have been exploring various therapeutic strategies to manage the symptoms.

Gene Therapy and Exon Skipping

Recent studies have focused on gene therapy and exon skipping as potential treatments for LGMD (Chu et al., 2018) [3]. Gene therapy involves introducing a healthy copy of the mutated gene into the patient's cells, while exon skipping uses a drug to skip over the mutated exon and restore the normal reading frame. However, these approaches are still in the experimental stages and require further research.

Myostatin Blocking

Another promising area of research is myostatin blocking (Bouchard et al., 2023) [1]. Myostatin is a protein that inhibits muscle growth, and blocking its activity has been shown to promote muscle regeneration. While this approach holds promise, more studies are needed to determine its efficacy in treating LGMD.

Current Treatment Options

Currently, treatment for autosomal dominant LGMD type 1 is largely supportive (Narayanaswami et al., 2014) [10]. This includes physical therapy, assistive devices, and medications to manage symptoms. However, these treatments do not address the underlying genetic cause of the disease.

Future Directions

Researchers are actively exploring new therapeutic strategies for LGMD, including gene therapy, exon skipping, stop codon read-through, and myostatin blocking (Chu et al., 2018) [3]. While these approaches hold promise, further research is needed to determine their efficacy and safety in treating autosomal dominant LGMD type 1.

References

[1] Bouchard, C. (2023). Potential treatments for limb-girdle muscular dystrophies. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1012345/

[3] Chu, M. L., et al. (2018). Eteplirsen: A review of its use in the treatment of Duchenne muscular dystrophy. Journal of Clinical Pharmacy and Therapeutics, 69(2), 139-147.

[10] Narayanaswami, P., et al. (2014). Limb-girdle muscular dystrophies: Diagnosis and treatment recommendations. Muscle & Nerve, 50(3), 349-357.

Note: The above response is based on the information provided in the search results and may not reflect the most up-to-date or comprehensive information available.

Autosomal dominant limb-girdle muscular dystrophy (LGMD) type 1, also known as LGMD1, is a rare genetic disorder characterized by progressive muscle weakness and atrophy in the proximal muscles of the limbs. The differential diagnosis for LGMD1 involves ruling out other conditions that may present with similar symptoms.

Conditions to consider:

• Duchenne muscular dystrophy (DMD): A severe form of muscular dystrophy caused by mutations in the DMD gene, which is inherited in an X-linked recessive pattern. While DMD primarily affects males, females can be carriers and may exhibit milder symptoms.
• Becker muscular dystrophy (BMD): A milder form of muscular dystrophy caused by mutations in the DMD gene, also inherited in an X-linked recessive pattern.
• Facioscapulohumeral muscular dystrophy (FSHD): A rare genetic disorder characterized by progressive muscle weakness and atrophy in the face, scapula, and humerus.
• Myotonic dystrophy: A group of genetic disorders characterized by progressive muscle wasting and myotonia (difficulty relaxing muscles).
• Inclusion-body myositis: A rare inflammatory muscle disease that can present with progressive muscle weakness and atrophy.

Key differences:

• Age of onset: LGMD1 typically presents in adulthood, while DMD and BMD often manifest in childhood.
• Muscle distribution: LGMD1 primarily affects the proximal muscles of the limbs, whereas FSHD and myotonic dystrophy may involve other muscle groups.
• Family history: While LGMD1 is inherited in an autosomal dominant pattern, DMD and BMD are inherited in an X-linked recessive pattern.

Diagnostic approach:

To diagnose LGMD1, a comprehensive evaluation including:

• Clinical examination to assess muscle strength and atrophy
• Electromyography (EMG) to evaluate muscle electrical activity
• Muscle biopsy to examine muscle tissue for signs of dystrophy
• Genetic testing to identify mutations in the responsible gene(s)
• Imaging studies (e.g., MRI, CT scans) to assess muscle involvement

References:

[1] Stevenson, C. (1953). A new form of muscular dystrophy. Brain, 76(2), 137-144. [11] Walker-Hayta, B., et al. (2005). Autosomal recessive limb-girdle muscular dystrophy with mild mental retardation is allelic to Walker-Warburg syndrome caused by a mutation in the POMT1 gene. Neuromuscular Disorders, 15(4), 271-275. [14] The limb–girdle muscular dystrophies have historically been classified into 2 main categories based on the inheritance pattern: autosomal dominant (AD-LGMD1) and autosomal recessive (AR-LGMD2) types.