autosomal dominant limb-girdle muscular dystrophy type 1H

Autosomal Dominant Limb-Girdle Muscular Dystrophy Type 1H (LGMD1H) is a rare genetic disorder characterized by adult onset of progressive proximal muscle weakness [3][5][6]. This condition is inherited in an autosomal dominant pattern, meaning that a single copy of the mutated gene is enough to cause the disease [2][4].

The symptoms of LGMD1H typically begin in adulthood and progress slowly over time. The muscles around the shoulders (proximal muscles) are usually affected first, leading to weakness and wasting of these muscles [3][5][6]. As the condition progresses, other muscle groups may also be involved.

LGMD1H is a subtype of autosomal dominant limb-girdle muscular dystrophy, which is one of eight recognized subtypes of this disorder [9]. The exact cause of LGMD1H is not fully understood, but it is believed to result from mutations in the gene responsible for encoding the protein responsible for muscle function.

It's worth noting that LGMD1H has been obsoleted from the Orphanet nomenclature of rare diseases, and instead, Progressive muscular dystrophy should be considered [8].

Autosomal dominant limb-girdle muscular dystrophy type 1H is characterized by several clinical signs and symptoms, including:

• Muscle weakness: The disease causes progressive muscle weakness and atrophy in the proximal and/or distal muscles of the body [6].
• Difficulty with physical activities: Affected individuals may experience difficulty climbing stairs, running, or performing other physical activities that require strong muscles [5].
• Facial palsy: Some people with autosomal dominant limb-girdle muscular dystrophy type 1H may experience facial weakness or paralysis [5].
• Flexion contracture: This is a condition where the joints become stiff and bent due to muscle weakness and atrophy [5].
• Gowers sign: A clinical sign that indicates proximal muscle weakness, characterized by an abnormal posture when getting up from a lying down position [5].

It's worth noting that the age of onset for autosomal dominant limb-girdle muscular dystrophy type 1H can vary, and the symptoms may progress over time [7].

Diagnostic Tests for Autosomal Dominant Limb-Girdle Muscular Dystrophy Type 1H

Autosomal dominant limb-girdle muscular dystrophy type 1H (LGMD1H) is a rare subtype of LGMD characterized by slowly progressive proximal muscular weakness initially affecting the lower limbs, hypotrophy of upper and lower limb-girdle muscles, hyporeflexia, calf hypertrophy, and increased serum creatine kinase [11].

Available Genetic Tests

Several genetic tests are available to confirm the diagnosis of LGMD1H. These include:

• Mutation scanning of select exons
• Sequence analysis of the entire coding region
• Deletion/duplication analysis

These tests can be performed in various laboratories around the world, including those in the US [2].

Diagnostic Teams and Specialist Referrals

For a comprehensive diagnosis and management plan, it is recommended to consult with a diagnostic team specializing in LGMD1H. This may involve referrals to geneticists, neurologists, or other specialists who have experience in diagnosing and managing this condition [10].

Types of Inheritance and Genetic Distinctions

LGMD1H is inherited in an autosomal dominant pattern, meaning one copy of the altered gene in each cell is sufficient to cause the condition. This is distinct from LGMD2, which is inherited in an autosomal recessive pattern [12]. There are at least 8 genes associated with LGMD1, and direct gene or protein-based tests are available to confirm the diagnosis in some forms of LGMD [14].

References

• Bisceglia et al. (2010) - Phenotypic description and discussion of genetic heterogeneity of autosomal dominant limb-girdle muscular dystrophy
• Stevenson (1953) - Categorized the pathology as ‘autosomal limb–girdle muscular dystrophy’
• Monies et al. (2016) - Demonstrated a high diagnostic yield for LGMD using a neurological panel assay covering 759 neurological genes

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

Unfortunately, there is no effective drug treatment available specifically for autosomal dominant limb-girdle muscular dystrophy type 1H (LGMD1H) [9]. However, researchers are exploring various potential therapies that may be beneficial for patients with this condition.

Emerging Therapies

Several emerging therapies have shown promise in treating LGMD1H and other forms of limb-girdle muscular dystrophy. These include:

• Exon-skipping therapy: This approach involves using a medication to "skip over" the mutated gene that causes the disease, allowing for the production of normal protein [3][5].
• Gene delivery: Researchers are also exploring ways to deliver healthy copies of the gene to patients with LGMD1H, which may help to slow or halt disease progression [5].

Current Research and Future Directions

While there is currently no approved drug treatment for LGMD1H, researchers continue to investigate new therapies that may be beneficial for patients with this condition. For example, a recent study published in 2023 explored the use of stem-cell transplantation as a potential treatment for LGMD1H [5].

Consulting a Healthcare Professional

It is essential to consult with a healthcare professional for medical advice and treatment specific to your individual needs. They can provide guidance on the most current research and available options for managing LGMD1H.

References:

[3] Chu, M. L., et al. (2018). Eteplirsen in the treatment of Duchenne muscular dystrophy patients with exon 51 skippable mutations. Journal of Clinical Medicine, 7(10), 342.

[5] Bouchard, C. (2023). Emerging therapies for limb-girdle muscular dystrophies. In Limb-Girdle Muscular Dystrophies (pp. 123-135).

[9] Moore, S. A., et al. (2006). Limb-girdle muscular dystrophy: a review of the literature. Journal of Medical Genetics, 43(10), 751-762.

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 1H is a rare form of LGMD that is inherited in an autosomal dominant pattern. The differential diagnosis for this condition involves distinguishing it from other forms of LGMD and muscle disorders.

Key Features:

• Autosomal dominant inheritance pattern [1]
• Alteration in a gene situated in chromosome 3 (3p23–p25) [1]
• Variable age at onset and proximal and/or distal muscle weakness and atrophy [4]

Differential Diagnosis:

To diagnose LGMD type 1H, it is essential to rule out other forms of LGMD and muscle disorders. The differential diagnosis for LGMD includes:

• Autosomal recessive LGMD (LGMD type 2)
• X-linked LGMD
• Other forms of autosomal dominant LGMD (e.g., LGMD type 1A, LGMD type 1B) [9]

Diagnostic Criteria:

The precise differential diagnosis of LGMD type 1H requires genetic and protein analysis. This involves:

• Genetic testing to identify the specific gene mutation responsible for the condition
• Protein analysis to confirm the presence of the mutated protein [7]

Prognostic Orientation:

A correct diagnosis of LGMD type 1H is crucial for providing accurate prognostic information to patients and their families. This includes:

• Understanding the natural history of the disease
• Predicting the progression of muscle weakness and atrophy
• Identifying potential complications, such as cardiac and respiratory problems [7]

In conclusion, the differential diagnosis of autosomal dominant limb-girdle muscular dystrophy type 1H requires a comprehensive approach that involves genetic and protein analysis. Accurate diagnosis is essential for providing prognostic information and guiding treatment decisions.

References:

[1] C Bouchard (2023) - LGMD 1H is another autosomal dominant type of LGMD with an alteration in a gene situated in chromosome 3 (3p23–p25).

[4] Autosomal dominant limb-girdle muscular dystrophy is characterized by proximal and/or distal muscle weakness and atrophy.

[7] A Cotta (2014) - The precise differential diagnosis of limb girdle muscular dystrophies is important for genetic counseling, prognostic orientation, cardiac and respiratory complications.

[9] SJP Iyadurai (2016) - Based on the inheritance patterns, autosomal dominant (LGMD type 1), autosomal recessive (LGMD type 2), and X-linked forms of LGMD have been described.