Myofibrillar Myopathy type 13 with Rimmed Vacuoles

MFM13 (previously known as HSPB8 myopathy) is an ultra-rare, autosomal dominant, slowly progressing, adult-onset muscle wasting condition. It is a type of Myofibrillar Myopathy and was first identified by Ghaoui et al, in 2015. It is caused by frameshift mutations in the Heat Shock Protein family B 8 (HSPB8) gene with around 60 cases identified worldwide so far (Ghaoui et al, 2016; Echaniz-Laguna et al, 2017; Cortese et al, 2018; Nicolau et al, 2020; Inoue-Shibui et al, 2021; Al-Tahan et al, 2019, Tan et al., 2024; Oommen et al, 2025; Tedesco et al., 2025). HSPB8 is a member of the Chaperone-assisted selective autophagy (CASA) complex, an important regulator of autophagy process in cells. Generally, HSPB8 acts like a quality control inspector in healthy cells. Its job is to help identify and manage damaged or misfolded proteins. When proteins in our cells fold incorrectly, they can cause problems, much like how a misshapen part can cause issues in a machine. The HSPB8 frameshift mutation despite losing its functionality in the CASA complex can still bind other members of the complex, leading to protein aggregation, such as HSPB8, p62 or BAG3 (known as cause of MFM5). This toxic gain of function mechanism results in autophagy impartment and finally muscle weakness. MFM13 is characterized by the morphological features of myofibrillar myopathy, including aggregates and rimmed vacuoles. Unfortunately, MFM13 is not routinely included in genetic myopathy panels and therefore heavily underdiagnosed.

What are the symptoms of MFM13?

The symptoms of MFM13 can vary among individuals but typically include a range of muscle-related issues. Here are some of the common symptoms:

Muscle Weakness: Progressive muscle weakness is a hallmark of this condition. It typically begins in the distal muscles, but cases with initial involvement in proximal muscles have also been reported (Tedesco et al, 2025, Supplementary Table 1). Over time, the weakness can spread to other muscle groups.

Muscle Wasting (Atrophy): Along with weakness, muscle wasting or atrophy may develop, especially in the affected muscle groups. This is due to the degeneration of muscle fibers.

Difficulties in daily life: Due to muscle weakness in the lower body, individuals may experience difficulty walking, which can progress to the need for mobility aids. Due to weakness in the upper limbs, individuals may experience trouble raising hands

Fatigue: General fatigue is common, which is not only due to muscle weakness but also the body's increased effort to compensate for the affected muscles.

Slow Progression: The symptoms typically progress slowly over time, and the rate of progression can vary from person to person.

It's important to note that the severity and combination of symptoms can differ significantly among individuals. Some may have mild symptoms for many years, while others may experience amore rapid progression. Diagnosis often involves muscle biopsies, genetic testing, and clinical examinations to confirm the presence of characteristic features like rimmed vacuoles in muscle fibers. However, a definite diagnosis can only be obtained with genetic testing, specifically by confirming frameshift mutations in the HSPB8 gene.

Cure MFM13

Cure MFM13 is the only charitable project and advocacy group dedicated to overcoming the challenges posed by MFM13. Our goal is to find a treatment and a cure for this ultrarare, debilitating condition, expand knowledge of the disease, realize the true number of patients, and support the community. Our vision is a future where MFM13 is conquered; treatments are accessible, and the community stands united. No one walks alone.

If you or your loved one is affected by MFM13 (previously HSPB8 myopathy), we are here for you. You can reach out to us, join our patient and families-dedicated, closed facebook group, follow us on X and fill out in the patient registry. On our website you can sign up for the mailing list, and you can always simply contact us at: ania@curemfm13.org

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