Unlocking the Mysteries of TPM2-Related Cap Myopathy: A Guide to Understanding, Diagnosing, and Genetic Testing

Expert Reviewed By: ⁠Dr. Brandon Colby MD

What is TPM2-Related Cap Myopathy?

TPM2-related cap myopathy is a rare genetic muscle disorder characterized by muscle weakness and the presence of abnormal structures called “caps” in muscle fibers. This condition is caused by mutations in the TPM2 gene, which encodes the protein β-tropomyosin. β-tropomyosin plays a crucial role in muscle contraction, and its dysfunction leads to muscle weakness in affected individuals.

Understanding the Pathogenesis of TPM2-Related Cap Myopathy

Recent research has begun to shed light on the underlying mechanisms of TPM2-related cap myopathy. A study by Marttila et al. (2012) investigated the pathogenetic mechanisms of five disease-causing mutations in the TPM2 gene. The researchers found that these mutations led to abnormal actin binding of aberrant β-tropomyosins, which may contribute to muscle weakness in patients with nemaline and cap myopathy.

Diagnosing TPM2-Related Cap Myopathy

Diagnosing TPM2-related cap myopathy can be challenging due to its rarity and the variability of its clinical presentation. However, a combination of clinical examination, muscle biopsy, and genetic testing can help to confirm the diagnosis. Muscle biopsy typically reveals the presence of caps in muscle fibers, which are characteristic of this disorder.

Genetic Testing for TPM2-Related Cap Myopathy

Genetic testing can be a valuable tool in confirming the diagnosis of TPM2-related cap myopathy and providing information for affected individuals and their families. Several studies have identified novel genetic mutations associated with this condition, expanding our understanding of its genetic basis.

Identifying Novel Genetic Mutations

Recent research has identified novel genetic mutations associated with TPM2-related cap myopathy and related disorders. A study by Kim et al. (2021) reported two patients with homozygous MYPN pathogenic variants, presenting as slowly progressive congenital myopathy. Another study by Wang et al. (2018) described a novel point mutation in the LDB3 gene, which is associated with Z-disc-associated, alternatively spliced, PDZ motif-containing protein-related myofibrillar myopathy (ZASP-MFM).

Expanding the Phenotypic and Genetic Spectrum

Genetic testing has also led to the identification of further phenotypic and genetic heterogeneity in TPM2-related cap myopathy and related disorders. A study by McEntagart et al. (2019) identified a recurrent heterozygous missense substitution in TPM2 in three unrelated individuals. This finding expands the range of TMP2-related phenotypes and suggests that de novo TMP2 mutations should be considered in isolated cases of multiple pterygium syndrome-related conditions.

Benefits of Genetic Testing

Genetic testing for TPM2-related cap myopathy can provide several benefits for affected individuals and their families. These include:

• Confirmation of diagnosis, which can help to guide appropriate management and treatment strategies
• Identification of carriers within a family, allowing for informed family planning and reproductive decision-making
• Improved understanding of the genetic basis of the condition, which can contribute to the development of targeted therapies

Conclusion

TPM2-related cap myopathy is a rare genetic muscle disorder with a complex genetic basis. Advances in genetic testing have greatly improved our understanding of this condition, allowing for more accurate diagnosis and the identification of novel genetic mutations. As research continues to uncover the genetic and phenotypic heterogeneity of TPM2-related cap myopathy, genetic testing will remain a valuable tool for affected individuals and their families.

About The Expert Reviewer

Dr. Brandon Colby MD is a US physician specializing in the personalized prevention of disease through the use of genomic technologies. He’s an expert in genetic testing, genetic analysis, and precision medicine. Dr. Colby is also the Founder of  and the author of ⁠⁠Outsmart Your Genes.

Dr. Colby holds an MD from the Mount Sinai School of Medicine, an MBA from Stanford University’s Graduate School of Business, and a degree in Genetics with Honors from the University of Michigan. He is an Affiliate Specialist of the American College of Medical Genetics and Genomics (⁠⁠ACMG), an Associate of the American College of Preventive Medicine (⁠⁠ACPM), and a member of the National Society of Genetic Counselors (⁠NSGC)