Introduction to HSPB8 Myopathy
What is HSPB8 Inclusion Body Myopathy with Rimmed Vacuoles?
HSPB8 Inclusion Body Myopathy with Rimmed Vacuoles (HSPB8 Myopathy) is a rare genetic muscle disorder. Let's break down the name:
Inclusion Body Myopathy: This term refers to a group of muscle diseases where abnormal protein aggregates, called inclusion bodies, are found in muscle cells. These inclusions are essentially clusters of proteins that shouldn't be there, and they interfere with normal muscle cell function.
HSPB8: This refers to the gene involved in this specific form of myopathy. Mutations in the HSPB8 gene disrupt the normal function of the HSPB8 protein, which, as previously mentioned, plays a crucial role in managing damaged or misfolded proteins in cells. The mutation leads to problems in protein folding and processing.
Rimmed Vacuoles: These are characteristic features seen in muscle fibers affected by this condition. They are small, empty spaces (vacuoles) surrounded by rings (or rims) of various proteins and debris. These vacuoles are visible when muscle tissue is examined under a microscope and are indicative of degenerating muscle fibers.
In layman's terms, HSPB8 Inclusion Body Myopathy with Rimmed Vacuoles is a condition where a genetic mutation causes the muscle cells to mishandle proteins, leading to the accumulation of abnormal protein clumps and the formation of distinctive vacuoles. This results in progressive muscle weakness and degeneration. The specific symptoms, severity, and progression can vary among individuals with the condition.
What are the symptoms of HSPB8 Myopathy?
The symptoms of HSPB8 inclusion body myopathy with rimmed vacuoles 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, often affecting the muscles closest to the center of the body (proximal muscles) like the hips and shoulders. Over time, the weakness can spread to other muscle groups.
Muscle Wasting (Atrophy): Along with weakness, there can be noticeable muscle wasting or atrophy, especially in the affected muscle groups. This is due to the degeneration of muscle fibers.
Difficulty Walking: Due to muscle weakness in the lower body, individuals may experience difficulty walking, which can progress to the need for mobility aids.
Muscle Cramps and Stiffness: Some people may experience muscle cramps or stiffness, which can be uncomfortable and affect mobility.
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 a more rapid progression of muscle weakness and atrophy. Diagnosis often involves muscle biopsies, genetic testing, and clinical examination to confirm the presence of characteristic features like rimmed vacuoles in muscle fibers.
What is the cause of HSPB8 Myopathy?
HSPB8 Inclusion Body Myopathy with Rimmed Vacuoles is caused by genetic mutations in the HSPB8 gene
Can mutations in HSPB8 gene be passed on from parent to child?
Yes, HSPB8 Myopathy can be passed on in families. These conditions are typically inherited in an autosomal dominant manner. This means that a mutation in just one of the two copies of the HSPB8 gene, which a person has, is sufficient to cause the disorder. If a parent has a mutation in the HSPB8 gene, there is a 50% chance for each child to inherit that mutation and potentially develop the condition.
However, the expression of the condition (phenotype) can vary greatly among individuals, even within the same family. Some individuals who inherit the mutation may exhibit symptoms of the disease, while others may have very mild symptoms or none at all. This variability is influenced by several factors, including genetic modifiers, environmental factors, and lifestyle.
It's important for individuals with a family history of HSPB8-related conditions, or those who are known carriers of a HSPB8 gene mutation, to consider genetic counseling. Genetic counselors can provide information about the risk of passing the condition to children and discuss the available options for family planning and genetic testing.
What is HSPB8 protein and what is its function in the human body?
HSPB8 is a type of protein in the human body, and its name stands for "Heat Shock Protein Family B (Small) Member 8."
Heat Shock Proteins (HSPs): These proteins are like the body's emergency response team. They are produced in response to stress, like high temperatures, to protect cells. Think of them as the body's way of coping with tough conditions.
Role of HSPB8: Specifically, HSPB8 acts like a quality control inspector in 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. HSPB8 helps to either fix these proteins or mark them for disposal, thus keeping the cell healthy and functioning properly.
Involvement in Muscle Function: HSPB8 has a significant role in muscle cells. Muscles are constantly active and under stress (like when we exercise), so they need effective ways to manage damaged proteins. HSPB8 helps ensure that muscle cells remain healthy by taking care of these problematic proteins.
In summary, HSPB8 is a crucial player in maintaining cellular health, especially under stress, by ensuring proteins are correctly folded and functioning. This is particularly important in muscle cells, where stress and damage can be more common due to physical activity.
Join the Registry
By completing the patient registry, you provide invaluable information about the symptoms and progression of HSPB8 myopathy, that cannot be obtained otherwise. Data collected is crucial in determining effects of potential therapies.
Only the patients know what it is like to live with HSPB8 Myopathy
What is a patient registry?
A patient registry is a structured database that collects standardized information about individuals diagnosed with a specific disease or condition. It serves as a vital resource for researchers, clinicians, and policymakers to gather comprehensive data on disease characteristics, treatments, and outcomes.
Why is it important to fill out a patient registry and update it annually?
Filling out a patient registry and keeping it updated annually is crucial because it helps researchers and healthcare providers understand the natural progression of the disease, evaluate treatment effectiveness, and monitor long-term outcomes. By contributing your information regularly, you directly support research efforts that can lead to advancements in treatments and care strategies for the disease.
What is CoRDs (Collaboration of Rare Diseases at Sanford)?
CoRDs is an initiative led by Sanford Research that aims to unite individuals affected by rare diseases, researchers, and healthcare providers. It provides a platform for patients to securely contribute their health information to a centralized registry. CoRDs fosters collaboration among stakeholders to accelerate research, improve disease management, and ultimately find cures for rare conditions
Is the registry only in English?
At the moment the registry is available in English and Japanese
How do I register?
By clicking this link
Practical Information
Unfortunately, at the moment, no formal standard of care exists for HSPB8 Myopathy. However, a standard of care has been developed and published for VCP (Valosin-containing protein) disease, thanks to the efforts of the Cure VCP advocacy group. VCP disease shares many overlapping features with HSPB8 Myopathy, especially related to myopathic symptoms, and the supportive therapies section below is based on the guideline described. The full document can be accessed via this link.
There is currently no approved treatment to slow down or stop HSPB8 myopathy, so care focuses on managing symptoms. Patients should visit a multidisciplinary clinic every six months, where they can see an interdisciplinary team including a neurologist, physical therapist, occupational therapist, speech-language pathologist, respiratory therapist, and social worker. This team will help manage symptoms like muscle weakness, breathing problems, and muscle cramps. Supportive measures, such as using mechanical aids and maintaining a healthy weight to avoid obesity, can also be helpful.
Exercise
Regular exercise programs of low to moderate intensity are recommended to help maintain muscle function, strength, flexibility, endurance, balance, and independence in daily activities. Staying active is important because inactivity can lead to further muscle weakness and loss of function. While maintaining current strength is important, targeted muscle strengthening exercises should be done with proper monitoring for some patients. Although exercise is recommended, there is still a lack of evidence on the best exercise plan specifically for HSPB8 myopathy. Assistive devices that can help include ankle foot orthotics, canes, walkers, wheelchairs, chair seat risers, mobile arm supports, and lift systems.
Respiratory Therapy
Respiratory therapy is crucial for monitoring and managing breathing function. Pulmonary function tests should be done at least once a year, measuring forced vital capacity (FVC) in both sitting and lying down positions. Timely use of chest physiotherapy, non-invasive ventilation, and devices that help with breathing in and out can be very beneficial.
Speech-Language Pathology
Assessing bulbar function, which involves the muscles used for speech and swallowing, is crucial because it is closely connected to breathing and nutritional health. Speech-language pathologists evaluate how well a person can swallow, their speaking rate, and overall clarity of speech. A swallow study, using techniques like videofluoroscopy or flexible endoscopy, can detect swallowing difficulties and guide targeted treatments.
Specific diets and supplements haven't been properly studied in individuals with HSBP8 myopathy. However, a lipid-enriched diet has been shown to improve survival and muscle health in mice with a similar condition, though more research is needed to confirm these effects in humans.
It's reasonable to recommend an anti-inflammatory diet. This diet should be rich in fruits and vegetables, whole grains, lean proteins, and fatty fish, while avoiding highly processed foods and products with preservatives, pesticides, and artificial ingredients. Additionally, there is some evidence that a Mediterranean diet, which is protective against dementia and cardiovascular disease, might also be beneficial for the patients.
Family monitoring
People with HSPB8 mutations who do not yet have muscle weakness, as well as family members at risk, should be regularly checked for early signs of muscle problems. This involves standard strength and functional tests conducted by a multidisciplinary team. If muscle weakness is detected, they should have regular follow-ups to monitor for any progression and consider possible interventions. These check-ups should occur every 6 to 12 months, or more frequently if the muscle weakness worsens more quickly.
Get Involved
Patient Stories
Todd King, patient.
I grew up playing sports. Basketball of course, which is effectively required when you are from Indiana, USA. But I also played any other sport I could do - baseball, wrestling, track and field - In fact, I was so good at (American) football that I was recruited by Division 1 colleges to play for them.
Even after college I remained athletically inclined - for example, I picked up hiking and running - I could still run a 5:20 mile into my early 30's.
So after being athletic my whole life, it was especially jarring to be diagnosed with a mysterious myopathy in my late 30's.
I shouldn't have been so surprised, as my uncle was diagnosed with a mystery muscle condition and we suspected others in the family had it as well. But I figured that given I was pretty athletic, I must have been spared.
I figured wrong.
At that point, I decided I was going to do something about it. So I reached out to dozens of academic researchers, trying to find someone who will work with me to figure out what our condition is. After 7 years of trying, in 2015 I finally found a researcher who agreed to work with me. And after a little more than a year later, we found the mutation - What a momentus event for our family!
Since then, we've been searching for a treatment. In the meantime though, my health has declined substantially. The list of maladies is quite lengthy, but it includes severe leg muscles weakness, dramatically lowered breathing capacity and constant hip pain, among other issues.
This has of course led to a dramatic dropoff in the quality of life for me, and my family. In fact, I've unfortunately become increasingly reliant on my family's support (esp my poor wife) to serve as caregivers. So it has impacted all of us.
But while my health and quality of life have waned, my resolve to find a treatment has not - I vow to my dying breath that a treatment for HSPB8 Myopathy will be developed.
External Resources
Umbrella Rare Disease organizations
For those affected by rare diseases, various organizations around the world offer support, advocacy, and resources. Below is a list of key umbrella organizations in the USA and Europe, each dedicated to advancing research, providing information, and improving the lives of individuals with rare diseases.
USA:
NORD (National Organization for Rare Disorders): NORD is a patient advocacy organization dedicated to individuals with rare diseases and the organizations that serve them. They provide patient assistance programs, advocacy, education, and research funding.
Global Genes: Global Genes is committed to connecting, empowering, and inspiring the rare disease community. They provide educational resources, advocacy tools, and support networks to patients and their families. Cure HSPB8 is a member of the Global Genes Alliance.
MDA (Muscular Dystrophy Association): MDA is focused on transforming the lives of people with muscular dystrophy, ALS, and related neuromuscular diseases through research, care, and advocacy.
Europe:
Treat NMD: Treat NMD is a network focused on accelerating the development of new treatments for neuromuscular diseases, offering resources and support for researchers, clinicians, and patients.
Beacon (formerly Findacure): Beacon supports the rare disease community by building a network of advocates, providing training, and promoting collaboration to advance research and patient care.
EURORDIS (European Organisation for Rare Diseases): EURORDIS is a non-profit alliance representing rare disease patient organizations in Europe, advocating for better policies and raising awareness to improve patient lives.
EJP RD (European Joint Programme on Rare Diseases): EJP RD aims to create a sustainable ecosystem for rare disease research, fostering collaboration between researchers, patients, and healthcare providers.
Human disease databases
Orphanet: Orphanet is a unique resource dedicated to rare diseases and orphan drugs. It provides expert-reviewed information on rare diseases, including epidemiology, clinical features, genetics, and available treatments. Orphanet aims to improve the diagnosis, care, and treatment of patients with rare disorders. HSPB8 Myopathy is described in Orphanet under this link.
GARD (Genetic and Rare Diseases Information Center): GARD is a program funded by the National Institutes of Health (NIH) that provides comprehensive information and resources on genetic and rare diseases. It offers a database of diseases, expert-reviewed information, genetic testing resources, and support for patients, families, and healthcare providers.
OMIM (Online Mendelian Inheritance in Man): OMIM is a comprehensive database of human genes and genetic phenotypes. It catalogues genetic disorders and their associated genes, offering detailed information on the genetic basis of inherited disorders, including clinical descriptions, genetic mapping, and links to relevant research articles. OMIM serves as a crucial resource for researchers, clinicians, and genetic counselors studying inherited diseases. We are working hard to get HSPB8 Myopathy it’s entry in OMIM.
Genetic data sharing platforms
Patients can work with their physicians to upload their genetic information into the genetic data sharing platforms below. The aims is to facilitate research and inform clinical practice:
MyGene2:
MyGene2 is an online platform that facilitates the sharing of genetic information among families affected by rare genetic conditions, researchers, and clinicians. Users can upload and share genetic data and clinical information to accelerate the discovery of new genetic causes of rare diseases and promote collaboration.
Who can upload data: Families affected by rare genetic conditions, researchers, and clinicians.
Purpose: To promote data sharing and collaboration, accelerating the discovery of genetic causes of rare diseases and providing a resource for families to connect with others who have similar genetic conditions.
Currently only one HSPB8 family is captured in MyGene2, and we encourage patients to update this information.
ClinVar:
ClinVar is a public archive that reports the relationships between human variations and phenotypes, with supporting evidence. Hosted by the National Center for Biotechnology Information (NCBI), it aggregates information about genomic variation and its relationship to human health.
Who can upload data: Clinicians, researchers, genetic testing laboratories, and other stakeholders in the genetics community.
Purpose: To provide a centralized resource that supports the sharing of information about the clinical significance of genetic variants, aiding in the interpretation of genetic data, supporting clinical decision-making, research, and the advancement of precision medicine.
Clin Var lists several mutations in HSPB8 gene. We encourage health care professionals to update ClinVar as soon as they are aware of a new case.
Genetic Testing
How do I get the DNA test for HSPB8 Myopathy?
Please talk to your doctor if you are interested in learning more about genetic testing for HSPB8. You may also wish to see a geneticist or genetic counselor, professionals who specialize in hereditary conditions, coordinating genetic tests, as well as explaining genetics, genetic testing, and the implications of genetic test results. The test uses saliva sample, and the results are av ailable in about 3 weeks.
There are a few different ways that your doctor can order the HSPB8 test. There are tests that look in specific sections of HSPB8 where known mutations have previously been found or there is a test of the entire HSPB8 gene or panel of genes. Please talk to your doctor about which of the tests are best for you or your family member.
How does DNA testing work?
The HSPB8 gene is tested by comparing it with a known “normal” gene to identify genetic changes that might lead to disease. The test uses DNA typically from a saliva sample or blood sample (less than 1 tablespoon of blood).
There are two reasons that a doctor might order the DNA test.
First, DNA testing can confirm a diagnosis of HSPB8 Myopathy for someone who has symptoms.
Second, DNA testing may also be used by people with a family history of HSPB8 Myopathy who do not have symptoms and want to find out whether they might develop the disease in the future. If possible, it is best to first test a family member with the symptoms of HSPB8 Myopathy. If the mutation that runs in a family is then known, carrier testing for other family members is much easier, less expensive, and the results are more meaningful.
If you have questions about whether genetic testing is right for you or your family members, please make an appointment with a geneticist or genetic counselor. These are professionals who specialize in inherited conditions and coordinating genetic tests. They are trained to explain genetics, genetic testing, and the implications of genetic test results.
What is the purpose of HSPB8 DNA testing?
HSPB8 Myopathy is often misdiagnosed as a different disease, and DNA testing is the only definitive way to diagnose it. An accurate diagnosis allows:
Doctors to determine if additional screening tests are necessary for other symptoms, enabling appropriate therapies (e.g., BiPAP for breathing difficulties).
Recommendations for lifestyle changes such as diet, nutrition, and exercise.
the opportunity to participate in research, aiding scientists in learning more about HSPB8 Myopathy.
Insight into who else in the family might develop the disease.
DNA testing for family members without symptoms to identify if they carry the mutation.
Testing of a pregnancy through amniocentesis (testing the fluid around the pregnancy) or chorionic villus sampling (CVS: testing a small sample of the placenta).
Preimplantation genetic diagnosis (PGD), a method of ensuring a pregnancy without the HSPB8 mutation. In PGD, sperm and egg are combined in a laboratory, embryos are tested for the HSPB8 gene, and only those without the familial mutation are implanted.
What are the risks of DNA Testing?
People who do not have any symptoms and are considering DNA testing for HSPB8 Myopathy should make an appointment with a geneticist or a genetic counselor. A person must carefully think through the reasons for wanting to get the test, whether they would want to know the results, and how both positive and negative results might affect their life and the lives of other family members. Discussing the testing with a geneticist or genetic counselor will allow a fully informed decision about whether to do the test or know the results. Genetics and genetic counselors are trained to relay results in a way that will be most helpful and least disruptive to a person’s life.
In the past there have been concerns about insurance and employment discrimination, especially for family members without any symptoms. In 2008 a bill called the Genetic Information Nondiscrimination Act (GINA) was passed. This law protects people from discrimination by insurance companies and employers based on genetic information
What does it mean if the DNA test comes back negative?
A negative DNA result means that no mutation was found in the parts of the HSPB8 gene that were tested. A negative result in an asymptomatic person in family with a known HSPB8 mutation means that this person will not develop HSPB8 Myopathy.
What does it mean if the DNA test comes back positive?
A positive DNA result means that a mutation that causes HSPB8 Myopathy was found in the HSPB8 gene. For someone experiencing symptoms a positive result confirms the diagnosis of HSPB8 Myopathy.