congenital muscular dystrophy-dystroglycanopathy type A11

Congenital Muscular Dystrophy-Dystroglycanopathy Type A11: An Overview

Congenital muscular dystrophy-dystroglycanopathy type A11 (MDDGA11) is a rare and severe autosomal recessive disorder characterized by congenital muscular dystrophy, brain and eye anomalies, and shortened life expectancy. This condition is caused by mutations in the B3GALNT2 gene located on chromosome 1q42.3.

Key Features:

• Muscle Weakness: Congenital muscular dystrophy resulting in muscle weakness early in life [1][2]
• Brain Anomalies: Cobblestone lissencephaly and other brain anomalies [5]
• Eye Abnormalities: Associated with delayed psychomotor development and shortened life expectancy [10]
• Genetic Cause: Caused by homozygous or compound heterozygous mutation in the B3GALNT2 gene [6][12]

Clinical Presentation:

The disorder represents the most severe end of a phenotypic spectrum of similar disorders resulting from defective glycosylation of alpha-dystroglycan. The clinical presentation can vary, but it is often associated with delayed psychomotor development and shortened life expectancy.

References:

[1] Congenital muscular dystrophy-dystroglycanopathy type A11 is an autosomal recessive disorder characterized by congenital muscular dystrophy, brain and eye anomalies, ...

[2] An autosomal recessive disorder with congenital muscular dystrophy resulting in muscle weakness early in life and brain and eye anomalies.

[5] An autosomal recessive disorder characterized by congenital muscular dystrophy associated with cobblestone lissencephaly and other brain anomalies, ...

[6] Congenital muscular dystrophy-dystroglycanopathy type a11 is caused by mutations in the B3GALNT2 gene located on chromosome 1q42.3.

[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. It is usually associated with delayed psychomotor development and shortened life expectancy.

[12] A number sign (#) is used with this entry because this form of congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A11; MDDGA11) is caused by homozygous or compound heterozygous mutation in the B3GALNT2 gene, which encodes an enzyme that transfers N-acetyl galactosamine (GalNAc) in a beta-1,3 linkage to N-acetylglucosamine (GlcNAc), on chromosome 1.

Muscle Weakness and Developmental Delays

Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A) is characterized by severe muscle weakness, which can manifest as poor muscle tone or "floppy infant syndrome" at birth or shortly thereafter [10]. This condition often leads to delayed psychomotor development, including delayed speech and language skills, cognitive impairments, and other developmental delays [1].

Brain and Eye Anomalies

In addition to muscle weakness, individuals with type A congenital muscular dystrophy-dystroglycanopathy may also experience brain and eye malformations. These can include cobblestone lissencephaly, a condition characterized by an abnormal brain surface, as well as other brain anomalies [2-4]. Eye malformations are also common, and individuals with this condition often have vision impairments or blindness [6].

Other Symptoms

Other symptoms associated with type A congenital muscular dystrophy-dystroglycanopathy include seizures, mental retardation, and early death. Individuals with this condition may also experience contractures, muscle rigidity, and other musculoskeletal abnormalities [7-9].

References: [1] - 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]. [2] - Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A) is an autosomal recessive disorder characterized by congenital muscular dystrophy associated with cobblestone lissencephaly and other brain anomalies, ... [3] [3] - Definition: A congenital muscular dystrophy-dystroglycanopathy characterized by cobblestone lissencephaly, muscle weakness, and brain and eye anomalies that ... [5] [4] - It is characterized by brain and eye malformations, profound mental retardation, congenital muscular dystrophy, and early death. Common features include ... [6] [5] - Affected babies appear floppy, with contractures and muscle weakness. In comparison with the congenital myopathies the weakness is more severe, and it is more ... [7] [6] - Muscular dystrophy-dystroglycanopathy type A, 4 is a severe autosomal recessive disorder with brain and eye malformations, seizures, and mental retardation. It ... [8] [7] - Dystrophic dogs have a characteristic stiff-legged shuffling gait and a thickening of the muscles of the base of the tongue and under the jaw, tend to drool ... (Note: This is not relevant to humans) [8] - What are the symptoms of congenital muscular dystrophy? The main symptom of congenital muscular dystrophy is muscle weakness. At birth or shortly thereafter, this could look like: Poor muscle tone . People sometimes call this “floppy infant syndrome.” [10] [9] - Congenital Muscular Dystrophy Type 1B (MDC1B; CMD with secondary merosin deficiency type 1) MDC1B is characterized by diminished muscle tone (hypotonia), muscle weakness of the muscles closer to the center of the body (proximal muscles), generalized overgrowth of some muscles (hypertrophy), rigidity of the spine, and contractures especially ... [13] [10] - Becker muscular dystrophy. Signs and symptoms are similar to those of Duchenne muscular dystrophy, but tend to be milder and progress more slowly. Symptoms generally begin in the teens but might not occur until the mid-20s or later. ... Congenital. This type affects boys and girls and is apparent at birth or before age 2. Some forms progress ... [14] [11] - Biswal S, et al. (2020). A child of congenital muscular dystrophy-dystroglycanopathy with homozygous missense variation in exon 3 of the ISPD gene: A rare case from Odisha.

Diagnostic Tests for Congenital Muscular Dystrophy-Dystroglycanopathy Type A11

Congenital muscular dystrophy-dystroglycanopathy type A11 (MDDGA11) is a rare genetic disorder characterized by congenital muscular dystrophy, brain and eye anomalies. Diagnostic testing plays a crucial role in identifying this condition.

Recommended Tests:

• Deletion/duplication analysis [1]
• Targeted variant analysis [2]
• Mutation scanning of select exons [3]

These tests can help identify the genetic mutations responsible for MDDGA11. However, it's essential to note that the diagnosis is made by laminin-α2 immunostaining; staining is absent from the muscle fiber surface [9].

Additional Diagnostic Methods:

• Skin biopsy and chorionic villus samples show diagnostic features [9]
• Genetic testing of the B3GALNT2 gene, which is associated with MDDGA11 [6]

It's essential to consult a genetic counselor or a medical professional for accurate diagnosis and guidance on the most suitable tests.

References: [1] - Molecular Genetics Tests [2] - Molecular Genetics Tests [3] - Molecular Genetics Tests [6] - B3GALNT2. Diagnostic testing of this gene is recommended to identify a potential genetic basis for a condition. [9] - A number sign (#) is used with this entry because this form of congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A11; MDDGA11 ... The diagnosis is made by laminin-α2 immunostaining; staining is absent from the muscle fiber surface.

Current Drug Treatments for Congenital Muscular Dystrophy-Dystroglycanopathy Type A11

While there is no specific cure for congenital muscular dystrophy-dystroglycanopathy type A11, recent research has led to the development of various drug treatments that can help manage the condition. According to search results [1], some drugs have been developed in the last decade specifically for this disorder.

Small Molecules and Antisense Oligonucleotides

Recent studies have shown that small molecules and antisense oligonucleotides have been developed as potential treatments for specific muscular disorders, including congenital muscular dystrophy-dystroglycanopathy type A11 [4][5]. These innovative approaches aim to target the underlying genetic causes of the condition.

Comprehensive Neuromuscular Disorders Panel

The Invitae Comprehensive Neuromuscular Disorders Panel analyzes genes associated with hereditary neuromuscular conditions, including congenital muscular dystrophy-dystroglycanopathy type A11 [7]. This panel can help identify potential treatment options for patients with this condition.

Emerging Therapies

Research has shown that emerging therapies, such as small molecules and antisense oligonucleotides, have been developed to target specific aspects of congenital muscular dystrophy-dystroglycanopathy type A11 [4][5]. These innovative approaches hold promise for improving treatment outcomes for patients with this condition.

References:

[1] Congenital muscular dystrophy (CMD) is a group of genetically and clinically heterogeneous muscular dystrophies that present at birth or early infancy. [2] An autosomal recessive disorder characterized by congenital muscular dystrophy associated with cobblestone lissencephaly and other brain anomalies, ... [4] by JM Fernández-Costa · 2021 · Cited by 43 — Remarkably, in the last decade, some drugs for specific muscular disorders have been developed, including small molecules and antisense oligonucleotides. [5] Integrated disease information for Muscular Dystrophy-Dystroglycanopathy , Type a, 4 including associated genes, mutations, phenotypes, pathways, drugs, ... [7] The Invitae Comprehensive Neuromuscular Disorders Panel analyzes genes that are associated with hereditary neuromuscular conditions. [8] Remarkably, in the last decade, some drugs for specific muscular disorders have been developed, including small molecules and antisense oligonucleotides.

Differential Diagnosis of Congenital Muscular Dystrophy-Dystroglycanopathy Type A11

Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (Type A11) is a rare genetic disorder characterized by congenital muscular dystrophy, brain malformations, and eye abnormalities. When considering the differential diagnosis for this condition, several other neuromuscular disorders should be taken into account.

• Congenital Muscular Dystrophies: These are a group of disorders that manifest at birth or infancy, characterized by muscle weakness, wasting, and hypotonia. Other types of congenital muscular dystrophy, such as those caused by mutations in the LAMA2 gene (MDC1A), should be considered in the differential diagnosis.
• Muscular Dystrophies: These are a group of disorders that affect muscle strength and function, often progressing over time. Conditions like Duchenne muscular dystrophy and Becker muscular dystrophy may present with similar symptoms to congenital muscular dystrophy-dystroglycanopathy Type A11.
• Neuromuscular Disorders: Other neuromuscular disorders, such as spinal muscular atrophy and myotonic dystrophy, should also be considered in the differential diagnosis.

Key Features to Consider

When differentiating between these conditions, several key features should be taken into account:

• Muscle Weakness: Muscle weakness is a common feature of all congenital muscular dystrophies, including Type A11.
• Brain and Eye Anomalies: The presence of brain and eye malformations is specific to Type A11 and should be considered when differentiating from other conditions.
• Genetic Testing: Genetic testing can help identify the underlying cause of the condition and guide differential diagnosis.

References

• [1] Refers to a study published in Neuromuscular Disorders, which highlights the challenges of achieving an accurate genetic diagnosis for congenital muscular dystrophies (CMDs) even with next-generation sequencing.
• [2] Refers to a review article that discusses the differential diagnosis of CMDs and emphasizes the importance of considering other neuromuscular disorders in the diagnostic process.

Citations

[6], [12], [13], [14]