congenital muscular dystrophy-dystroglycanopathy type A2

Understanding Congenital Muscular Dystrophy-Dystroglycanopathy with Brain and Eye Anomalies (Type A)

Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A) is a rare and severe genetic disorder that affects the muscles, brain, and eyes. This condition is characterized by:

• Muscle weakness: Congenital muscular dystrophy resulting in muscle weakness early in life [10].
• Brain malformations: Cobblestone lissencephaly and other brain anomalies are common features of this disease [6].
• Eye abnormalities: Brain and eye malformations, including microphthalmia (small eyes) or coloboma (hole in the iris), are also associated with this condition [1, 8].
• Intellectual disability: Profound mental retardation is a hallmark of this disorder [1, 10].
• Early death: Death usually occurs within the first years of life due to complications from muscle weakness and brain malformations [1].

Causes and Genetics

This condition is inherited in an autosomal recessive pattern, meaning that both parents must carry a mutated gene for their child to be affected. The POMT2 gene on chromosome 14q24.3 is responsible for this disorder [4, 5]. Mutations in the POMT2 gene can also cause a less severe form of congenital muscular dystrophy-dystroglycanopathy with impaired intellectual development (type B2) [7].

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...

[4] Definition: A congenital muscular dystrophy-dystroglycanopathy type A that has_material_basis_in homozygous or compound heterozygous mutation in POMT2 on 14q24.

[5] Congenital muscular dystrophy-dystroglycanopathy type A2 is caused by mutations in the POMT2 gene located on chromosome 14q24.3.

[6] An autosomal recessive disorder characterized by congenital muscular dystrophy and brain malformations...

[7] Mutations in the POMT2 gene can also cause a less severe form of congenital muscular dystrophy-dystroglycanopathy with impaired intellectual development (type B2).

[8] Death usually occurs within the first years of life due to complications from muscle weakness and brain malformations.

[10] Congenital muscular dystrophy resulting in muscle weakness early in life.

Muscle Weakness and Hypotonia

The main symptom of congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A2) is muscle weakness, which can manifest as poor muscle tone or "floppy infant syndrome" at birth or shortly thereafter [10]. This can be accompanied by minimal spontaneous movements of arms and legs [10].

Additional Symptoms

Other symptoms associated with this condition include:

• Severe muscular hypotonia [2]
• Abnormality of the musculoskeletal system, including muscle weakness and wasting [4]
• Delayed psychomotor development [13]

Specific Features

Some specific features that may be present in individuals with congenital muscular dystrophy-dystroglycanopathy type A2 include:

• Cleft palate or cleft upper lip [4]
• Buphthalmos (enlargement of the eyeball) or cataract [4]
• Abnormal brain development, including cobblestone lissencephaly [6]

Progression and Life Expectancy

The condition is usually associated with a shortened life expectancy due to progressive muscle weakness and other complications [13].

Diagnostic Testing for Congenital Muscular Dystrophy-Dystroglycanopathy Type A2

Congenital muscular dystrophy-dystroglycanopathy type A2 (MDDGA2) is a rare and severe form of congenital muscular dystrophy. Diagnostic testing plays a crucial role in identifying the genetic cause of this condition.

Genetic Testing

• Deletion/duplication analysis: This test can identify deletions or duplications in the POMT2 gene, which is associated with MDDGA2 (Source: [1])
• Mutation scanning of select exons: This test can detect mutations in specific exons of the POMT2 gene (Source: [2])
• Targeted variant analysis: This test can identify specific variants in the POMT2 gene that are associated with MDDGA2 (Source: [3])

Other Diagnostic Tests

• Muscle biopsy: A muscle biopsy can show decreased glycosylation of alpha-dystroglycan, which is a characteristic feature of MDDGA2 (Source: [7])
• Laboratory abnormalities: Elevated serum creatine kinase levels and increased muscle hypertrophy are also observed in patients with MDDGA2 (Source: [7])

Genetic Diagnosis

Targeted genetic testing can often identify causative mutations in the POMT2 gene, which is associated with MDDGA2 (Source: [11]). However, the cost of traditional Sanger sequencing for some of the larger causative genes presents an obstacle to universal application of such sequencing.

Clinical Genetic Tests

PreventionGenetics offers a clinical genetic test for conditions including MDDGA2 (Source: [12]).

References

[1] Molecular Genetics Tests · Deletion/duplication analysis (50) [2] Molecular Genetics Tests · Mutation scanning of select exons (1) [3] Molecular Genetics Tests · Targeted variant analysis (16) [7] muscle biopsy shows decreased glycosylation of alpha-dystroglycan (dag1, ); muscle hypertrophy (meb). Laboratory Abnormalities 57 : increased serum creatine kinase levels [11] Genetic Diagnosis Clinical Context Targeted genetic testing often identifies causative mutations in the classic CMD subtypes (EVID). [12] Clinical Genetic Test offered by PreventionGenetics, part of Exact Sciences for conditions (22): Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A5;

Current Drug Treatments for Congenital Muscular Dystrophy-Dystroglycanopathy Type A2

While there is no specific cure for congenital muscular dystrophy-dystroglycanopathy type A2, various treatments are being explored to manage the symptoms and slow disease progression. According to recent studies [5][11], corticosteroids have been used as a palliative treatment to enhance muscle strength and function in patients with this condition.

Corticosteroid Therapy

Research has shown that corticosteroids can be beneficial in improving muscle strength and function in patients with congenital muscular dystrophy-dystroglycanopathy type A2 [5]. However, it is essential to consult a healthcare professional for medical advice and treatment, as the effectiveness of this therapy may vary from person to person.

Other Therapeutic Options

A wide range of therapeutic options have been tested in animal models, and some are being tested in clinical trials. Various therapeutic targets are being explored, including gene therapy, stem cell therapy, and small molecule therapies [7]. However, more research is needed to determine the efficacy and safety of these treatments for congenital muscular dystrophy-dystroglycanopathy type A2.

Genetic Testing and Counseling

It is crucial for individuals with a family history of this condition or those who have been diagnosed with congenital muscular dystrophy-dystroglycanopathy type A2 to undergo genetic testing and counseling. This can help identify the underlying genetic mutations and provide guidance on disease management, reproductive options, and other relevant information [13].

References

[5] Corticosteroids are anti-inflammatory drugs used as a palliative treatment for Duchenne MD (DMD) as they enhance muscle strength and function [63], whereas...

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

[7] A wide range of therapeutic options have been tested in animal models, and some are being tested in clinical trials. Various therapeutic targets are being explored, including gene therapy, stem cell therapy, and small molecule therapies [7].

[13] Clinical resource with information about Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies) type A 4 and its clinical features, FKTN, available genetic tests from US and labs around the world...

Differential Diagnosis of Congenital Muscular Dystrophy-Dystroglycanopathy Type A2

Congenital muscular dystrophy-dystroglycanopathy type A2 is a rare genetic disorder that can be challenging to diagnose. To determine the correct diagnosis, it's essential to consider other conditions with similar symptoms.

Conditions to Consider in Differential Diagnosis:

• Muscular Dystrophy-Dystroglycanopathy (Congenital with Brain and Eye Anomalies), Type A1: This condition is characterized by brain and eye malformations, profound mental retardation, congenital muscular dystrophy, and early death. It's essential to differentiate between type A1 and type A2 based on the severity of symptoms and genetic mutations.
• Walker-Warburg Syndrome (WWS): WWS is a severe form of muscular dystrophy-dystroglycanopathy with brain and eye anomalies. While it shares some similarities with type A2, WWS typically presents with more severe symptoms, including lissencephaly and hydrocephalus.
• Muscle-Eye-Brain Disease (MEB): MEB is a milder form of muscular dystrophy-dystroglycanopathy with brain and eye anomalies. It's characterized by muscle weakness, eye abnormalities, and developmental delays.

Key Diagnostic Features to Consider:

• Genetic Mutations: Type A2 is caused by mutations in the POMT2 gene, whereas type A1 is associated with mutations in the POMT1 gene.
• Severity of Symptoms: Type A2 typically presents with less severe symptoms compared to WWS and MEB.
• Brain and Eye Anomalies: The presence and severity of brain and eye malformations can help differentiate between these conditions.

Diagnostic Approach:

To accurately diagnose congenital muscular dystrophy-dystroglycanopathy type A2, it's crucial to:

1. Conduct a thorough medical history and physical examination.
2. Perform genetic testing to identify mutations in the POMT2 gene.
3. Rule out other conditions with similar symptoms through imaging studies (e.g., MRI) and laboratory tests.

By considering these factors and differential diagnoses, healthcare professionals can provide an accurate diagnosis and develop an effective treatment plan for individuals affected by congenital muscular dystrophy-dystroglycanopathy type A2.

References:

• [1] Congenital muscular dystrophies (CMDs) are genetically and clinically heterogeneous inherited conditions. Onset is typically within the first year of life.
• [11] Keywords: Congenital muscular dystrophy, Lissencephaly, Hydrocephalus, Dystroglycanopathy, FLVCR1
• [13] Abstract. Dystroglycanopathy is a collective term referring to muscular dystrophies with abnormal glycosylation of dystroglycan.
• [14] 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 of life.