autosomal dominant limb-girdle muscular dystrophy type 2

Autosomal Dominant Limb-Girdle Muscular Dystrophy Type 2

Limb-girdle muscular dystrophy (LGMD) is a group of disorders characterized by progressive muscle weakness and wasting, primarily affecting the muscles around the shoulders and hips. LGMD type 2 includes forms of the disorder that have an autosomal dominant inheritance pattern.

Key Features:

• Inheritance Pattern: Autosomal dominant, meaning a single copy of the mutated gene is enough to cause the condition.
• Age of Onset: Can occur at any age, but often presents in adulthood.
• Muscle Affected: Primarily affects the muscles around the shoulders and hips (limb-girdle area).
• Progression: Gradual muscle weakness and wasting over time.

Subtypes:

LGMD type 2 is further divided into several subtypes, each caused by mutations in different genes. Some of these subtypes include:

• LGMD2A (now LGMD R1): Caused by recessive mutations in the CAPN3 gene.
• LGMD-2L: An autosomal recessive subtype secondary to ANO5 gene mutation.

Prevalence and Age of Onset:

LGMD type 2 is relatively rare, with a prevalence of approximately 1-9 per 100,000 people. The age of onset can vary widely, but it often presents in adulthood.

References:

• [3] Classified by the respective inheritance patterns: autosomal dominant and autosomal recessive.
• [4] Prevalence: 1-9 / 100 000; Inheritance: Autosomal dominant, Autosomal recessive; Age of onset: All ages.
• [5] LGMD R group: These LGMDs happen due to autosomal recessive inheritance patterns.

Initial Symptoms

The initial symptoms of autosomal dominant limb-girdle muscular dystrophy type 2 (LGMD2A) often include weakness and wasting (loss of muscle bulk) in the hip, thigh, and shoulder muscles [5]. This weakness is usually progressive and may spread to affect other muscles of the body.

Common Features

The common features to all people with LGMD2A will be weakness of the big muscles of the legs and/or arms. This may result in frequent falls, difficulty walking, and muscle atrophy (shrinkage) [8].

Progressive Weakness

Muscle weakness and atrophy are progressive and may spread to affect other muscles of the body [3]. The age at which symptoms appear, and the speed and progression of the disease can vary from person to person.

Specific Symptoms

Specific symptoms related to hip and upper leg muscle weakness include a waddling gait, difficulty standing up from a seated position, and weakness in the proximal leg muscles [1].

Clinical Features

The clinical features of LGMD2A may also include abnormality of limbs (pelvic girdle muscle weakness; shoulder girdle muscle weakness), abnormality of metabolism/homeostasis (elevated creatine kinase levels), and progressive weakness and muscle atrophy involving the shoulders, pelvic girdle, or both [7].

General Signs and Symptoms

The general signs and symptoms of LGMD2A include progressive weakness and muscle atrophy involving the shoulders, pelvic girdle, or both. The age of onset, severity, and progression of the disease can vary from person to person [9].

Autosomal dominant limb-girdle muscular dystrophy (LGMD) type 1 can be diagnosed through a combination of clinical assessment, specialized muscle immunoanalysis, and genetic testing.

• Clinical Assessment: A thorough medical history and physical examination are essential to diagnose LGMD type 1. The condition typically presents with progressive weakness and wasting of the muscles in the pelvic and shoulder girdles [13].
• Specialized Muscle Immunoanalysis: This test can help identify specific muscle proteins that are affected in LGMD type 1. However, it is not a definitive diagnostic tool on its own.
• Genetic Testing: Genetic testing is the most accurate method for diagnosing autosomal dominant LGMD type 1. It involves analyzing DNA samples to identify mutations in the genes responsible for the condition [14]. Improved and more specific genetic testing has enabled better diagnosis of this subtype.

In addition, muscle imaging with computed tomography (CT) may also be used to support the diagnosis of LGMD type 1 by showing characteristic changes in muscle structure [5].

It's worth noting that a combination of clinical assessment, specialized muscle immunoanalysis, and genetic testing is usually required for an accurate diagnosis.

Autosomal dominant limb-girdle muscular dystrophy (LGMD) type 2 refers to a group of rare genetic disorders characterized by progressive muscle weakness and wasting, primarily affecting the muscles around the shoulders and hips. While there is no specific treatment available for LGMD, research has been exploring various therapeutic strategies.

Current Treatment Options

According to recent studies [4][5], several rare forms of autosomal dominant limb-girdle muscular dystrophy are inherited in an autosomal dominant pattern, meaning one copy of the altered gene is sufficient to cause the condition. However, there is no specific treatment available for LGMD type 2.

Emerging Therapies

Research has been investigating various emerging therapies that may potentially benefit individuals with LGMD [9]. These include:

• Gene therapy: This involves using genes to replace or repair faulty genes responsible for the condition.
• Exon skipping: A technique that allows the production of a functional protein by "skipping" over the mutated exon.
• Stop codon read-through: A strategy that enables the production of a functional protein by bypassing the stop codon, which normally signals the end of protein synthesis.
• Myostatin blocking: This involves inhibiting the action of myostatin, a protein that regulates muscle growth and development.

While these emerging therapies hold promise, they are still in the experimental stages, and more research is needed to determine their efficacy and safety for LGMD type 2.

Supportive Care

The primary focus of treatment for autosomal dominant limb-girdle muscular dystrophy remains supportive care [6][7]. This includes:

• Physical therapy: To maintain mobility and functional independence
• Assistive devices: Such as wheelchairs, walkers, or other adaptive equipment to aid in daily activities
• Medications: To manage associated symptoms, such as pain or muscle spasms

It is essential for individuals with LGMD type 2 to work closely with their healthcare providers to develop a personalized treatment plan that addresses their specific needs and promotes optimal quality of life.

References:

[4] Sep 1, 2019 — Several rare forms of limb-girdle muscular dystrophy are inherited in an autosomal dominant pattern...

[5] Oct 1, 2019 — Learn about Limb-Girdle Muscular Dystrophies, including symptoms, causes, and treatments.

[6] Sep 17, 2024 — The treatment of Limb-Girdle muscular dystrophy focuses on supportive care to maintain mobility and functional independence...

[7] Dec 12, 2023 — Treatment involves managing symptoms with various strategies, like physical therapy, assistive devices and medications.

[9] To learn more, read The Changing Landscape of LGMD...

Differential Diagnosis of Autosomal Dominant Limb-Girdle Muscular Dystrophy Type 2

Autosomal dominant limb-girdle muscular dystrophy (LGMD) type 2 is a rare genetic disorder that affects the muscles around the shoulders and hips. The differential diagnosis for this condition involves ruling out other similar conditions that may present with similar symptoms.

Conditions to Consider:

• Rigid Spine Syndrome: This condition is characterized by stiffness in the spine, elbow, and ankle contractures, as well as limited flexion of the spine. It often presents with mild and slowly progressive myopathy.
• Duchenne Muscular Dystrophy (DMD): Although more common than LGMD type 2, DMD can present with similar symptoms, including muscle weakness and wasting around the shoulders and hips.
• Becker Muscular Dystrophy: This is a milder form of DMD that also presents with muscle weakness and wasting around the shoulders and hips.

Key Diagnostic Features:

• Muscle MRI: Involvement of upper limb girdle and paravertebral muscles, as well as lower limb girdle and posterior compartment of the thigh.
• Genetic Testing: Autosomal dominant inheritance pattern, with mutations in genes such as FKRP or TRIM32.

References:

• [11] More than 20 different forms of LGMDs are known, including at least 7 autosomal dominant and 14 autosomal recessive. The existing clinical overlap makes their differential diagnosis difficult.
• [10] The differential diagnosis includes rigid spine syndrome, which in addition to elbow and ankle contractures, usually is associated with very limited flexion of the spine, relatively mild and slowly progressive myopathy.
• [9] The disorder fulfills LGMD diagnostic criteria,21 with the following clinical features: slowly progressive proximal symmetric weakness with predominantly lower limb involvement.

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