Dear Dr. Viacheslav Pauls

Desmin is a muscle-specific type III intermediate filament protein interlinking myofibrils at the level of the Z-disc and connecting them to other cellular organelles thus maintaining the structural and functional integrity of the muscle cell. Mutations of the human desmin gene on chromosome 2q35 cause autosomal dominant, autosomal recessive, and sporadic myopathies and/or cardiomyopathies with marked phenotypic variability.

The muscle pathology is characterized by desmin-positive protein aggregates and degenerative changes of the myofibrillar apparatus. The molecular pathophysiology of desminopathies is a complex, multi-level issue. In addition to direct effects on the formation and maintenance of the extra-sarcomeric intermediate filament network, mutant desmin affects essential protein interactions, cell signaling cascades, mitochondrial functions, and protein quality control mechanisms.

Thus, desmin-related myopathy leads to intracellular accumulation of misfolded protein and production of soluble pre-amyloid oligomers, which can lead to weakened skeletal and cardiac muscle.

In patients with desmin mutations, the earliest and most consistently affected muscle at mid-thigh is semitendinosus, followed by sartorius and gracilis. These are the early and predominant signs of desminopathies.

You may want to refer to the article attached below for more information.

Article Desminopathies: Pathology and mechanisms

Regards,

Malcolm Nobre

Surprisingly, despite the fact that desmin (the affected protein in desminoipathy) content is very high in Purkinje fibres and diaphragmatic muscle cells affected muscles are skeletal.

Dear Malcolm Nobre and Bhoj R Singh, thank you very much for your replies and the link to the article. But, unfortunately, the presented article does not contain information about the possible causes of selective damage in the early stages of desminopathy specifically to the Semitendinosus, Gracilis and Sartorius muscles, and not to other muscles. How can this pattern be explained?

Desminopathy refers to a group of rare genetic muscle disorders characterized by mutations in the desmin gene. Desmin is a protein that provides structural support and stability to muscle fibers. When it is compromised, it can lead to muscle weakness and degeneration.

The specific muscles you mentioned - the semitendinosus, gracilis, and sartorius - are often affected at the onset of desminopathy due to a few reasons:

1. Fiber Type Composition: These muscles predominantly contain slow-twitch (Type I) muscle fibers. Slow-twitch fibers are rich in mitochondria and are responsible for endurance activities. In desminopathy, these fibers are more susceptible to degeneration and dysfunction.

2. Functional Overload: The semitendinosus, gracilis, and sartorius muscles are often involved in activities that require repetitive or prolonged use. Over time, this repetitive stress can exacerbate the degeneration of muscle fibers in the presence of desminopathy.

3. Intrinsic Susceptibility: Some muscles are inherently more susceptible to muscle disorders due to their structure and function. In desminopathy, certain muscles may have a higher predisposition to develop muscle weakness and degeneration compared to others.

It is important to note that the exact mechanisms underlying the pattern of muscle involvement in desminopathy are still being studied, and individual variations can occur. Consulting with a healthcare professional or genetic specialist would be the best way to fully understand how desminopathy specifically affects the semitendinosus, gracilis, and sartorius muscles in an individual case.

Dear Shler Ali Khorsheed, thank you very much for your detailed answer!

Dear Tony McCabe, thank you very much for your answer and feedback! Most often, patients before the manifestation of desminopathy were physically strong and resilient (up to 20-30 years of age), this is with a late onset of the disease. The available literature on desminopathy lacks studies aimed at understanding differences in muscle groups and the reasons for their deterioration. The required volume and nature of physical exercise for desminopathy is not yet known, most often it is individual. Evidence of greater damage to slow or fast fibers in desminopathy is contradictory. This is most likely due to a mutation in the desmin gene in a homozygous or heterozygous state, the domain region, and the stage of the disease. With desminopathy, it is better to avoid heavy and prolonged physical exercise, the formation of lactic acid in the muscles. In my opinion, exercise should be light, low intensity, and short in duration. In addition to physical exercise, muscle condition is affected by nutrition, natural and climatic conditions, sleep duration, the patient’s lifestyle, the expression of other genes, etc.

Desminopathy, also known as desmin-related myopathy (DRM), is a rare genetic muscle disorder that affects the protein desmin. Desmin is an essential component of the intermediate filaments that provide structural support within muscle cells. Mutations in the DES gene, which codes for desmin, lead to disruptions in the normal structure and function of muscle fibers.

The muscles you mentioned - Semitendinosus, Gracilis, and Sartorius - are often affected at the onset of desminopathy due to their specific characteristics and biomechanical roles.

1. Semitendinosus: The semitendinosus is one of the three hamstring muscles located in the back of the thigh. It plays a key role in knee flexion and hip extension. The semitendinosus muscle is frequently involved in desminopathy due to its high proportion of slow-twitch muscle fibers, which are more vulnerable to desmin-related abnormalities.

2. Gracilis: The gracilis muscle is a long, thin muscle located in the inner thigh region. It is involved in hip adduction and knee flexion. Similar to the semitendinosus, the gracilis muscle also consists of a high proportion of slow-twitch muscle fibers, making it susceptible to desmin-related abnormalities.

3. Sartorius: The sartorius muscle is a long, strap-like muscle that runs diagonally across the front of the thigh. It plays a role in hip and knee flexion and also assists in thigh rotation. The sartorius muscle is affected in desminopathy due to its similar composition of slow-twitch muscle fibers.

The predilection for these specific muscles in desminopathy may be attributed to their fiber type composition and the mechanical stress they experience during certain movements. However, it is important to note that desminopathy can affect other muscles as well, and the degree and pattern of muscle involvement may vary among individuals with the same genetic mutation.

It is advised to consult with a medical professional or genetics specialist for a more accurate assessment of muscle involvement and management of desminopathy.