February 2022

Colleen Kienbaum, BSN, RN

Reducing Body Myopathy

Reducing Body Myopathy (RBM) is a rare muscle disorder marked by progressive muscle weakness and the presence of characteristic inclusion bodies in affected muscle fibers according to the National Institutes of Health (NIH). It is a congenital disease involving the nervous system. There are very few reported cases worldwide and Reducing Body Myopathy is listed as a rare disease with the NIH. Reducing Body Myopathy is most commonly diagnosed in infancy and early childhood though late-onset cases have been reported in older children and adults as well. The disease tends to be progressive, with infancy and early childhood diagnoses typically bringing about a more severe prognosis.

Skeletal muscle weakness is a hallmark of Reducing Body Myopathy with frequent falls, gait abnormalities and head drop common early manifestations of the disease. According to the NIH, difficulty feeding and cardiomyopathies are reported in 5%-29% of those diagnosed with Reducing Body Myopathy as well. Contractures can occur and affected muscle fibers can be both upper and lower or they may present as asymmetrical.

To diagnose Reducing Body Myopathy, a biopsy will be taken from muscle and evaluated with staining utilizing electron microscopy to look for characteristic “reducing” bodies. In those with Reducing Body Myopathy, a fine granular material will be seen and the presence of aggresome-like proteins will be confirmed by chemical analysis. There is a lot about Reducing Body Myopathy that is still poorly understood, including the pathophysiology of the disease.

Researchers know that it is caused by mutations in the gene encoding the four-and-a-half LIM domain 1 protein (FHL1). A mutation in the FHL1 gene leads to Reducing Body Myopathy and the clinical presentation of muscle weakness. However, how that mutation causes the weakness is poorly understood. According to MedLink Neurology, it is believed that the reducing body inclusions from the FHL1 mutation may be intimately related to muscle mass and function and therefore explain why the muscle weakness is so greatly affected in those with Reducing Body Myopathy.

Reducing Body Myopathy has a variable disease path. MedLink Neurology states the disease can be chronic and benign to progressive and severe due to variable penetrance of the FHL1 mutations. It has a familial X-linked inheritance pattern though sporadic non-familial cases have been reported and it can affect both males and females. Age of disease onset as well as severity can vary widely. Development up until the age of two is generally normal. Those diagnosed in infancy or early childhood have a more severe form of myopathy that is rapidly progressive

leading to respiratory insufficiency within five years. Older children and adults diagnosed are more likely to experience slower progression of the disease with proximal muscle weakness and a rigid spine. Variability of the disease can range even when multiple members of the same family are affected. Generally, the prognosis is severe, with muscle weakness leading to loss of ambulation and eventually, death due to respiratory failure with cardiomyopathies thought to

contribute as well.

Due to the rapid and severe nature of Reducing Body Myopathy, research and clinical trials are imperative to helping find a cure. Anyone diagnosed with a muscle disorder can help further research by allowing shared data and insight into a disease’s natural path of progression. The congenital muscle disease international registry (CMDIR) is leading the way to a cure. Please click here for more information on CMDIR and its work with clinical trials.

Please consider becoming part of the cure and donating to the Aubrey O’Sullivan Foundation today to help further research and help find a cure for those battling Reducing Body Myopathy.