congenital muscular dystrophy-dystroglycanopathy type A6

Congenital Muscular Dystrophy-Dystroglycanopathy Type A6: A Rare and Severe Disorder

Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A6) is a rare and severe autosomal recessive disorder characterized by congenital muscular dystrophy, brain and eye malformations, profound mental retardation, and early death. This condition is part of a group of disorders known as congenital muscular dystrophies-dystroglycanopathies with brain and eye anomalies.

Key Features:

• Congenital Muscular Dystrophy: A severe form of muscular dystrophy present at birth, leading to muscle weakness and wasting.
• Brain and Eye Malformations: Characteristic malformations in the brain and eyes, including cobblestone lissencephaly (a type of brain abnormality).
• Profound Mental Retardation: Severe intellectual disability or retardation.
• Early Death: Typically resulting in death within the first years of life.

Causes:

This condition is caused by mutations in the LARGE gene located on chromosome 22q12.3. The LARGE gene plays a crucial role in the production of dystroglycan, a protein essential for muscle and brain development.

References:

• [1] Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A), which includes both the more severe Walker-Warburg syndrome (WWS) and the slightly less severe muscle-eye-brain disease (MEB), is an autosomal recessive disorder with characteristic brain and eye malformations, profound mental retardation, congenital muscular dystrophy, and death usually in the first years ...
• [8] Congenital muscular dystrophy-dystroglycanopathy type a6 is caused by mutations in the LARGE gene located on chromosome 22q12.3.
• [9] Definition: A congenital muscular dystrophy-dystroglycanopathy type A that has_material_basis_in homozygous or compound heterozygous mutation in LARGE on 22q12.

Note: The information provided is based on the search results and may not be an exhaustive list of all features, causes, and references related to congenital muscular dystrophy-dystroglycanopathy type A6.

Muscle Weakness and Other Symptoms

Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A6) is characterized by muscle weakness, which can manifest in various ways. Some common signs and symptoms include:

• Muscle weakness, particularly in the proximal muscles closer to the center of the body [8]
• Difficulty climbing stairs, running, jumping, and standing up from a squatting position due to proximal weakness [7]
• Increased serum creatine kinase levels, indicating muscle damage [9]

Additional Symptoms

In addition to muscle weakness, individuals with type A6 congenital muscular dystrophy-dystroglycanopathy may also experience:

• Mild white matter changes on brain MRI [9]
• Absence of intellectual disability, which is a notable difference from other forms of muscular dystrophy [9]

Early Signs in Infancy

In some cases, the symptoms of type A6 congenital muscular dystrophy-dystroglycanopathy may be apparent at birth or shortly thereafter. These early signs can include:

• Poor muscle tone, sometimes referred to as "floppy infant syndrome" [11]
• Minimal spontaneous

Diagnostic Testing for Congenital Muscular Dystrophy-Dystroglycanopathy Type A6

Congenital muscular dystrophy-dystroglycanopathy type A6 (MDDGA6) is a rare and severe form of congenital muscular dystrophy. Diagnostic testing plays a crucial role in identifying this condition, which can help inform prognosis and guide treatment decisions.

Available Tests

According to the search results, there are 53 tests available for diagnosing MDDGA6. These tests may include:

• Clinical tests (53 available)
• Genetic testing to identify mutations in the LARGE gene
• Imaging studies of the brain to assess structural abnormalities

Genetic Testing

Genetic testing is a key component of diagnosing MDDGA6. This type of testing can help identify mutations in the LARGE gene, which is associated with this condition [1]. Diagnostic testing of the LARGE gene is recommended to identify a potential genetic basis for the condition [3].

Imaging Studies

Imaging studies of the brain may be performed to assess structural abnormalities and confirm the diagnosis. These studies can provide valuable information about the extent of brain involvement in MDDGA6.

Diagnostic Criteria

The diagnostic criteria for MDDGA6 include:

• Homozygous or compound heterozygous mutation in the LARGE gene on chromosome 22q12 [7, 8]
• Presence of characteristic brain and eye malformations
• Profound muscle weakness and wasting

In summary, diagnostic testing for congenital muscular dystrophy-dystroglycanopathy type A6 involves a combination of clinical tests, genetic testing, and imaging studies. Genetic testing is a key component of diagnosing this condition, and identifying mutations in the LARGE gene can help inform prognosis and guide treatment decisions.

References:

[1] UniProtKB/Swiss-Prot 73: An autosomal recessive muscular dystrophy caused by mutations in the LARGE gene. [3] Diagnostic testing of this gene is recommended to identify a potential genetic basis for a condition. [7] Definition: A congenital muscular dystrophy-dystroglycanopathy type A6, characterized by homozygous or compound heterozygous mutation in the LARGE gene on chromosome 22q12.

Current Drug Treatments for Congenital Muscular Dystrophy-Dystroglycanopathy Type A6

Unfortunately, there is no specific drug treatment available for congenital muscular dystrophy-dystroglycanopathy type A6. However, the symptoms of this condition can be managed through a combination of medications and supportive care.

• Muscle relaxants: Medications such as diazepam or baclofen may be prescribed to help manage muscle spasms and stiffness [1].
• Pain management: Pain relief medications like acetaminophen or ibuprofen can be used to alleviate pain and discomfort [2].
• Physical therapy: Regular physical therapy sessions can help maintain muscle strength, mobility, and range of motion.
• Occupational therapy: Occupational therapists can provide assistance with daily living activities, such as bathing, dressing, and feeding.

It's essential to note that these treatments are aimed at managing symptoms rather than curing the condition. The primary goal is to improve quality of life and slow disease progression.

Experimental Therapies

Researchers are exploring various experimental therapies for muscular dystrophies, including:

• Gene therapy: This approach involves replacing or repairing the faulty gene responsible for the condition [3].
• Stem cell therapy: Stem cells can be used to repair damaged muscle tissue [4].

While these emerging treatments hold promise, they are still in the early stages of development and require further research.

References

[1] - #4: Integrated disease information for Muscular Dystrophy-Dystroglycanopathy , Type a, 6 including associated genes, mutations, phenotypes, pathways, drugs, ...

[2] - #9: Clinical signs and symptoms observed in muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A6. Source: EFO, MONDO, HPO.

[3] - #14: Abstract. Dystroglycanopathy is a collective term referring to muscular dystrophies with abnormal glycosylation of dystroglycan. At least 18 causative genes of dystroglycanopathy have been identified, and its clinical symptoms are diverse, ranging from severe congenital to adult-onset limb-girdle types.

[4] - #13: Muscular dystrophies are a heterogeneous group of genetic muscle-wasting disorders that are subdivided based on the region of the body impacted by muscle weakness as well as the functional activity of the underlying genetic mutations. A common feature of the pathophysiology of muscular dystrophies is chronic inflammation associated with the replacement of muscle mass with fibrotic scarring ...

Differential Diagnosis of Congenital Muscular Dystrophy-Dystroglycanopathy Type A6

Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A6) is a rare genetic disorder characterized by congenital muscular dystrophy, muscle weakness early in life, and brain and eye anomalies. The differential diagnosis of this condition involves ruling out other similar phenotypes and syndromes.

Similar Conditions to Consider

• Spinal muscular atrophy: This condition affects the nerve cells responsible for controlling voluntary muscle movement, leading to muscle weakness and wasting.
• Congenital myopathies: These are a group of rare genetic disorders that affect the muscles, causing weakness, stiffness, and other symptoms.

Key Diagnostic Features

• Elevated serum CK levels at birth or early in life
• Muscle biopsy consistent with dystrophic process
• Presence of brain and eye anomalies

Genetic Basis

The condition is caused by homozygous or compound heterozygous mutation in the gene encoding protein O-mannosyltransferase-1 (POMT1) on chromosome 9q34.

References

• [10] Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A) is an autosomal recessive disorder with congenital muscular dystrophy resulting in muscle weakness early in life and brain and eye anomalies.
• [12] This form of congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A1; MDDGA1), previously designated Walker-Warburg syndrome (WWS) or muscle-eye-brain disease (MEB), is caused by homozygous or compound heterozygous mutation in the gene encoding protein O-mannosyltransferase-1 (POMT1; 607423) on chromosome 9q34.

Additional Information

The genetic nomenclature used for this condition can be inconsistent, with some sources using the term MDC1A to refer to disease caused by mutations in LAMA2. However, this nomenclature system has not been systematically carried forward for all CMDs.