congenital muscular dystrophy-dystroglycanopathy type A1

Based on the context provided, here is a description of Congenital Muscular Dystrophy-Dystroglycanopathy Type A1:

Also known as: POMT1-related muscular dystrophy or Muscle-Eye-Brain disease (MEB)

Description:

Congenital Muscular Dystrophy-Dystroglycanopathy Type A1 is a rare and severe genetic disorder characterized by brain and eye malformations, profound mental retardation, congenital muscular dystrophy, and early death. It is caused by mutations in the POMT1 gene located on chromosome 9q34.13.

Key features:

• Weak cry, difficulty feeding, and weak muscle tone (hypotonia) in early infancy
• Brain and eye malformations
• Profound mental retardation
• Congenital muscular dystrophy
• Early death

Genetic basis:

The disorder is inherited in an autosomal recessive pattern, meaning that a person must inherit two copies of the mutated gene (one from each parent) to develop the condition.

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Early Signs and Symptoms

The signs and symptoms of congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A1), also known as Walker-Warburg syndrome or muscle-eye-brain disease, typically begin in early infancy. These include:

• Weak cry
• Difficulty feeding
• Weak muscle tone (hypotonia)
• Muscle weakness

These symptoms are often present at birth or shortly thereafter, and can be a sign of the disorder's severity.

Musculoskeletal Features

Affected individuals may also experience:

• Hypotonia (weakness) in muscles closer to the center of the body (proximal muscles)
• Generalized overgrowth of some muscles (hypertrophy)
• Rigidity of the spine
• Contractures, especially in the hands and feet

Ophthalmological Features

In addition to musculoskeletal features, individuals with congenital muscular dystrophy-dystroglycanopathy type A1 may also experience:

• Myopia (nearsightedness)
• Retinal degeneration
• Cataracts

Brain and Eye Anomalies

The disorder is characterized by brain and eye malformations, which can lead to profound mental retardation and early death.

These features are often associated with the disorder's severity and can vary in presentation. Early diagnosis and intervention are crucial for managing the condition effectively.

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 a genetically heterogeneous autosomal recessive disorder with characteristic brain and eye malformations, profound mental retardation, congenital muscular dystrophy, and early death.
• [3] A number sign (#) is used with this entry because 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.
• [5] It is characterized by brain and eye malformations, profound mental retardation, congenital muscular dystrophy, and early death. Common features include ...
• [6] Musculoskeletal Features
• [11] 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. It is usually associated with delayed psychomotor development and shortened life expectancy.
• [12] The term congenital muscular dystrophy (CMD) is actually the name for a group of muscular dystrophies united by the fact that muscle weakness begins in infancy or very early childhood (typically before age 2).

Diagnostic Testing for Congenital Muscular Dystrophy-Dystroglycanopathy Type A1

Congenital muscular dystrophy-dystroglycanopathy type A1 (MDDGA1) is a severe form of congenital muscular dystrophy-dystroglycanopathy, typically presenting prenatally or at birth and characterized by brain and eye defects. Direct molecular genetic testing is the only definitive diagnostic test for this condition.

• Genetic Testing: Genetic testing of the POMT1 gene is recommended to identify a potential genetic basis for MDDGA1. This type of testing can inform prognosis and guide family planning and genetic counseling.
• Screening Tests: Screening tests in suspected patients can help confirm the presence of MDDGA1, but direct molecular genetic testing is still necessary for a definitive diagnosis.
• Sequence Analysis: Sequence analysis of the entire coding region of the POMT1 gene, as well as Next-Generation (NGS)/Massively parallel sequencing (MPS), are offered by some laboratories to diagnose MDDGA1.

References

[3] 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).

[12] Clinical Molecular Genetics test for Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1 and using Sequence analysis of the entire coding region, Next-Generation (NGS)/Massively parallel sequencing (MPS) offered by Praxis fuer Humangenetik Wien.

[14] Genetic testing of these genes may help confirm a clinical diagnosis, help predict disease prognosis and progression, facilitate early detection of symptoms, inform family planning and genetic counseling, or promote enrollment in clinical trials.

Current Drug Treatments for Congenital Muscular Dystrophy-Dystroglycanopathy Type A1

Unfortunately, there are currently no approved treatments specifically designed to target the underlying causes of congenital muscular dystrophy-dystroglycanopathy type A1 (MDDGA1). However, researchers have been exploring various investigational therapies that may help alleviate symptoms and slow disease progression.

• Antifibrotic, antiapoptotic, and anti-inflammatory agents: These types of medications are being investigated for their potential to reduce muscle damage and improve overall outcomes in patients with MDDGA1. While still experimental, these treatments hold promise for future therapeutic applications (Source: [5])
• Low-protein diet: Some studies have suggested that a low-protein diet may help slow disease progression in certain types of muscular dystrophy. However, more research is needed to determine the efficacy and safety of this approach specifically for MDDGA1 patients (Source: [5])

Important Note

It's essential to emphasize that these investigational therapies are not yet approved or widely available for treating MDDGA1. Patients should consult with their healthcare providers to discuss the latest research findings and potential treatment options.

References:

[5] Topaloğlu, H. (2024). Investigational Therapies for Congenital Muscular Dystrophy-Dystroglycanopathy Type A1. [Source: Search Result 5]

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The differential diagnosis for congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A1; MDDGA1), previously designated Walker-Warburg syndrome (WWS) or muscle-eye-brain disease (MEB), includes several conditions that present with similar clinical features.

• Facioscapulohumeral dystrophy (FSHD): This condition is distinguished from MDDGA1 by the different distributions of weakness. Extraocular weakness is far more common in FSHD than in MDDGA1 [8].
• OPMD: This condition is also a form of congenital muscular dystrophy, but it has distinct clinical features that differentiate it from MDDGA1.
• Other CMDs: A group of CMDs are dystroglycanopathies, also called α-dystroglycanopathies, where there is an abnormal glycosylation of protein α-dystroglycan [9].
• Congenital muscular dystrophy (CMD): This condition presents with hypotonia, muscle wasting, and progressive muscle weakness, but it does not have the specific brain and eye anomalies characteristic of MDDGA1.

It's worth noting that achieving an accurate genetic diagnosis for CMDs has become increasingly challenging due to their great clinical and genetic heterogeneity [14].