Patient Community Demands More Focus on the Clinical, Physical and Psychosocial Burdens of Facioscapulohumeral Muscular Dystrophy (FSHD)

Jennifer Brout, adult patient with FSHD, extended family members also affected;Michele Langer, adult patient and mother to adult daughter with FSHD;Kristen Zwickau, mother of pediatric daughter with FSHD

Reviewed for technical accuracy by Peter Jones, Associate Professor, Mick Hitchcock Endowed Chair of Medical Biochemistry, Peter and Takako Jones Lab for FSHD University of Nevada, Reno School of Medicine, Reno, Nevada.

ABSTRACT: According to leaders of the patient community, the 135-year-old definition of facioscapulohumeral muscular dystrophy (FSHD) is outdated and inadequately reflects the devastating nature of symptoms and the severe burden of this rare, variably progressive disease. For patients, every moment this disease remains underappreciated or underrecognized means continued muscle wasting, physical decline and inevitable hardship.

After discovery by Landouzy and Dejerine in 1884, FSHD was renamed in 1950 by its clinical features, which appeared to be weakness in the face (facio), shoulders (scapula), and upper arms (humerus) (Tyler and Stephens, 1950). In 1982, George Padberg, MD, PhD, published the definitive clinical characterization of the disease in his seminal thesis “Facioscapulohumeral Disease.” The Padberg thesis is probably the most referenced paper in the FSHD field. Unfortunately, the fact that it was published in 1982, more than 12 years before genetic testing for FSHD became available, demonstrates it obsolescence. Since 1993 when the gene location was found, there has been an increase in studies related to FSHD among a small group of interested researchers. However, the patient community feels that most doctors are still unfamiliar with this research and that the name of the disease and the disease itself continue to cause great confusion.

The common “look” of an FSHD patient was characterized by protruding winged shoulder blades and a mouth that was partially or fully immobilized due to muscle loss (resembling that of a person who has had a stroke). The disease has been further characterized as “moving down” toward the lower half of the body, affecting muscles in the core and the legs. Particularly notable is the impact that FSHD has on the feet, causing “foot drop,” making it difficult for people to walk. However, among current FSHD researchers (e.g., Johnson et al., 2012; Tawil, 2018) it is clear that this disease can strike a myriad of skeletal muscles in the body, rendering an unpredictable presentation as well as an unpredictable disease trajectory. While the disease biology is generally understood, the rate of progression is heterogeneous and can vary throughout the course of the disease.

Most research in FSHD has so far related to the underlying genetic mechanisms of the disease and potential of disease intervention. As a result, the catastrophic nature of living with FSHD has been obscured. While one in five people with FSHD are known to be in a wheelchair by age 50, this statistic (if still accurate) does not reflect the significant percentage of patients who are otherwise highly compromised, using wheelchairs some of the time as well as scooters, walkers, rollators, and other adaptive equipment. This statistic does not describe the early onset cases of FSHD, in which young children are in wheelchairs before they have reached adolescence. This statistic does not reflect the numbers of infants born with FSHD, referred to as having “infantile onset.” This statistic does not describe the debilitating pain experienced by over 70 percent of patients, the impact muscle loss has on general health or the fact that FSHD carries several serious health complications (such as breathing difficulties, cardiac problems, hearing loss and retinal problems) that are little known even in the medical community. It does not reflect either the variability of FSHD, with a disease course that differs from individual to individual. Finally, the social and emotional burden on patients as well as their caregivers also remain under reported.

In response to growing frustration in the patient community regarding clinical definitions and assumptions about FSHD, a group of patients joined together to present a first-hand range of perspectives to reflect the impact of FSHD more accurately on patients and caregivers. Following is an outline of their perspectives on the real-world effects of FSHD, the patient community’s collective experience living with the burden of FSHD, and the urgent need for safe and effective treatments.

Perspectives from the FSHD patient community

The current definition of FSHD does not adequately describe the extent of the disease progression and the devastating toll it takes on the body.

FSHD is typically associated with weakening and atrophy of muscles of the neck and shoulder blades and muscles at the front and back of the upper arms (biceps and triceps brachii muscles), slowly progressing downward to the core, legs, ankles and feet (rarediseases.org).

In our real-world experience, FSHD is a much more aggressive and disabling disease than has been characterized on many trusted medical websites and in academic literature. While the primary focus in clinical definitions of FSHD focuses on the upper body, muscles can be affected globally- not just in the face, shoulder blades and upper arms. Patients also experience progressive decline and loss of abdominals, gluteal muscles, hip abductors, quadriceps, hamstrings, soleus (calf), the tibialis anterior and ankle dorsiflexors. We must focus more on the impact in these areas to support optimal care. Moreover, the core muscles of the abdomen and the muscles of the back, the paraspinal muscles, are often severely affected. This makes getting out of bed difficult and interferes with one’s posture, making it difficult to walk, increasing the risk of falls, and often causing significant upper and lower back pain.

Many patients also experience moderate to severe negative impact on breathing due to loss of diaphragm function. One of the most devastating and often under-acknowledged results of having FSHD is the need for breathing assistance such as BiPAP and ventilators. Diaphragm weakness also places patients at increased risk for breathing difficulties during surgeries that require anesthesia.

“For years doctors told my brother he had COPD. Nobody ever gave him a BiPAP and he just suffered. I guess they weren’t looking at the research or the research just wasn’t out there.” - Caregiver

Severe manifestations of FSHD may also be associated with sleep-disordered breathing (SDB), including obstructive sleep apnea (OSA) and nocturnal hypoventilation (NH), but prevalence data are scarce. In patients with respiratory muscle weakness, detection of NH can be facilitated by transcutaneous capnometry, but respective data derived from FSHD patients have not yet been published (Runte, Spiesshoefer, & Heidbreder, et al, 2019).

“My cousin went in for surgery and the doctor told him that when he woke up he would be permanently on a ventilator because of the FSHD. He refused the surgery. Luckily another hospital was able to do it without this permanent complication, but it was a close call.”

Although respiratory weakness is a relatively unknown feature of FSHD, it is not uncommon. One study reported that almost all patients will develop restrictive lung disease and 10–20% will suffer from pulmonary complications (Hazenberg, van Alfen, Voet,Kerstjens, & Wijkstra, 2015). Unfortunately, FSHD is often referred to as not being a life-threatening disease, with patients having a normal life span. However, individuals with severe FSHD can die due to complications associated with their disease-induced respiratory insufficiency and associated altered blood chemistry. FSHD can in fact shorten one’s life.

The long-term cardiac effects on FSHD patients are also poorly understood and there is reason for great concern. One patient stated, “Recently I was diagnosed with atrio-ventricular block, which the cardiologist attributed to FSHD. There is no history of cardiac disease in my family. Although this type of arrhythmia is for the most part benign, it can become significant in the presence of future cardiac pathology. So now I can add this to the list of things I have to worry about!”

The focus on the impact of FSHD on the upper extremities is well documented, but it is often incomplete. For example, there is not wide reference to the fact that upper facial weakness can lead to the inability to completely close the eyes during sleep. This can lead to severe dry eyes, corneal scratches and poor sleep. In early, childhood onset FSHD, retinal vascular abnormalities can occur and lead to blindness. Additionally hearing loss, sometimes requiring hearing aids, can occur in childhood onset FSHD.

While the disease biology is generally understood, the rate of progression is heterogeneous and can vary. This variability is important to consider in planning for treatment. Patients report both physical and emotional deterioration associated with progressive and unpredictable decline. As one patient, a nurse living with FSHD, said, “FSHD creates a consistent grieving process – when you finally adjust to current progressive changes, in a short time you progress further and create a new grieving cycle. Any hope is dashed.”

Patients also note that it is imperative to take steps to try to slow or halt any progression before patients experience a decline in skills and abilities. According to one patient, “Three years ago, I was flying to Iceland. Now I can barely go for a walk.”

The complications of the disease are financially and emotionally devastating, and lead to serious issues in daily living and poor quality of life.

While clinical definitions of FSHD do focus on the impact on mobility, these assessments often do not tell the whole story. Noting that 20% of patients need a wheelchair by age 50 does not make clear that many must be lifted by other people or by using expensive equipment including personal lift systems. These systems can be unreliable and difficult to operate and are often not covered by insurance.

In addition, statistics on the use of wheelchairs can make it sound like all other patients are doing fine. In fact, many are also severely disabled despite being ambulatory. Patients report being unable to stand or walk without assistance. Many who can walk still cannot stand from a chair, climb stairs, or walk without falling or without support from a walker or rollator. Many become housebound, with one patient reporting, “I was an outside person all my life...now I never leave the house.”

The burden on caregivers can also be extremely challenging. Because of muscle decline, many patients cannot feed themselves or bathe on their own. Some cannot roll over in bed, which can lead to extraordinary pain and infection from pressure wounds. Problems with daily living can extend to basic hygiene when patients can be unable to lift their arms to wash, brush their teeth or comb their hair. For patients who do not have one or a team of caregivers, there is a risk of more rapid decline and a range of health and safety risks. One patient reported, ?“I wanted to get a walk-in tub but then I realized I couldn’t get up from the seat. Why don’t they make ones with variable seat heights?” Another stated, “I’m a grown woman wearing a diaper – this is beyond what I ever thought my life would be.”

Because of the physical burden of FSHD, patients often feel at risk or simply do not have the strength or will to leave their home. “I can walk but I cannot step up into any car or van that is high. You would be surprised how many cars are hard to get into, and I can’t take buses.” And another individual with FSHD commented, “I want to go visit my son, but I am terrified to take a train because of that space that sometimes occurs between the platform and the train – I’m scared I won’t make it, or I’ll fall.”

Weakness, instability, and immobility caused by FSHD, mean that many patients are unable to work and must rely on caregivers and home healthcare aids. The financial burden can be extensive. Most patients require frequent visits to medical specialists and must use numerous prescription medications and medical equipment including wheelchairs, walkers, lifts such as the Hoyer for the bedridden, stairway lifts, mechanical chair lifts, and BiPAP machines and must adapt their homes to accommodate this special equipment. Health insurance often does not cover all essential equipment and many other needs. The financial burden often falls on patients and families. “This year I had to move to a house with no stairs. I am lucky I could do so. I hear horrible stories every day from my fellow FSHD friends who can’t even afford lifts to help them get out of bed. People try to help each other – like Go Fund Me – but it’s endless. The thought of someone unable to get out of their bed is bad enough, add to it that they can’t afford anything to help,” one patient reported. ?

What also remains under reported is the comorbidity of FSHD and clinical depression. Patients report that they live in fear, chronic pain and social isolation while they battle a progressive and debilitating disease with no approved treatment options. “The definition of mental health is the ability to adapt to life’s circumstances. There is no way to adapt to an unpredictably progressive disease like FSHD,” stated a psychologist living with FSHD. Feelings of poor self worth and lack of hope are common. “I’m damaged goods. Who will want me?” stated a 25-year-old living with FSHD.

Patients report living with anxiety about the future and feelings of being a burden to caregivers. “I thought my husband and I would be spending our latter years enjoying life. Yet now my husband has to do so much for me. I am so grateful but sometimes I wonder what he is thinking.”

The inability to smile and move normally often leaves FSHD patients vulnerable to social misunderstanding by others. These further decrease self-esteem and contribute to social isolation.

Time is mobility: patients, family and caregivers are desperate for?access to any forms of treatment that could potentially stop disease progression as we are in a race against time.?

For those living with FSHD and those who care for them, there is a constant focus on time. As it passes, patients decline. And as an underserved and underrecognized community, many patients feel a loss of hope and debilitating despair. Patients need a treatment to halt or even slow progression.

One parent with an adult child with FSHD shared, “My daughter is struggling to have a baby having gone through five IVF cycles with pregenetic testing. She wonders if she is being selfish to even want children as she may not be able to physically care for them without assistance. She doesn’t go to pool parties due to back deformity and is unable to participate with her husband or friends in anything athletic or outdoor activities. She fears her husband will eventually reject her as the burden of disease becomes too much.”?

Disability extends beyond the reported signs and symptoms of FSHD. Patients are often unable to exercise, and many are at risk of poor cardiovascular health. Statins can cause rhabdomyolysis, a dangerous and painful breakdown of muscle, so many patients with FSHD have been told that they cannot be prescribed this medication.?Many patients gain weight easily because of lack of mobility, which can lead to more negative health issues and poor quality of life. “My doctor tells me to lose weight, but I only eat 1200 calories per day. Without movement the body just doesn’t lose weight. Carrying around the extra weight makes it harder to move. It’s a vicious cycle. My health is so compromised. I just want to give up.” And other patients are severely underweight. One patient commented, “Having so little muscle, I have a friend who is in his late 40s, weighs 72 pounds and can’t gain weight. How long can someone live like that?”

In the race against time with FSHD, bones are often weakened and atrophied. Bones can break and tendons can tear easily. Falls are a major concern. According to one individual with FSHD, “I’ve had two shoulder surgeries due to full thickness tears bilaterally. This adds to already weakened arms.”

Over time with a progressive disease there is also a risk of overuse of pain medications. One caregiver shared, “My brother and mother live with levels of pain that are beyond what anyone could imagine.”

Our call to action from the patient community

The full physical, emotional, and financial burdens of FSHD is vastly under reported and underappreciated. FSHD should be characterized as life limiting, with periods of rapid progression and loss of muscle, strength, and independence. It is a disease that results in chronic pain, anxiety and clinical depression. Current standards of care that work to address individual symptoms are not enough. It is imperative for healthcare providers, health insurance organizations, researchers and regulatory authorities to act with more urgency to seek and support potential treatments to slow or halt the progression of this disease. Time is not on our side. We must act as a collective community to recognize the burden of FSHD on patients and their caregivers, support research into treatments to slow or halt the devastating, burdensome, and life-limiting progression of FSHD. Discussion

Q. What is it like to get the diagnosis of FSHD?

Kristen: The day Kate was diagnosed was the biggest life changing day my husband and I have ever faced. We had this amazing spirited little girl and were the perfect trio, and with one diagnosis this bright future we saw for her was no longer. That future and the dream of watching her grow was at first replaced by hours upon hours of research trying to navigate and understand something that so few truly understand and that has no road map. Instant questions: Can she stay in the same school she is in? Can she go to summer camp? Do we have to quit our jobs? Do we need to move from the house she loves and knows as her safe place? Do we need to move out of Boston due to the harsh winters? Do we have the right insurance that will give us access to what we need to support her? The list goes on and on and on. FSHD is now a part of our life every day and we know we can never escape the reality of the debilitating disease.

Michele: I experienced one of the best days of my life the day my daughter was born. She has brought her father and me so much joy. The thing is, I didn’t know I had FSHD when I got pregnant. There were signs everywhere, but the diagnosis remained a mystery. I feel somewhat responsible for “giving” this to her even though I know this is irrational thinking. I have struggled greatly with this condition in immeasurable ways but none of this compares to knowing that she has the same neuromuscular disease. I am no longer her direct caretaker but worry about her future all the same. Will she be able to continue working? ?Will her marriage survive? Will she be able to have children? Will she be strong enough to cope with the ever-changing course this disease takes?

Q. How did receiving a diagnosis of FSHD change you?

Kristen: We no longer dream about our daughter’s future. It became too scary.?So now we live in today and do everything in our power to shut off future thoughts. One thing we focused on and fast was changing our lives so that Kate has the best chances of slowing her progression and building whatever muscle we can as she grows. Growth, hormones, and the genetic cause of the disease…it’s like the perfect storm brewing inside this perfect child.

Q. How has FSHD affected your family?

Jennifer: FSHD has been a part of my family for generations. My aunt, who passed away recently, had symptoms of FSHD that began as a child. She always walked with a limp. By the time she was in her 50s she could no longer walk. By the time she was in her 60s she could not get out of bed. She lay in bed for over ten years, unable to wash or use the toilet. Throughout all of this, she kept her sense of humor and when we talked she made me laugh! One day this year, seemingly out of nowhere, her oldest son and caregiver notified the family that she was in the hospital. She had an infected pressure wound and aspiration pneumonia. I won’t describe the details of her two-week long, drawn-out death because it is beyond what I can manage to share. It is inhuman how she suffered. The doctor explained clearly to the family that “there is nothing we can do…this disease is killing her.” One of the last things she said in the hospital was this: “I am ready to die but how can I leave [my son].” Her son is also severely affected by FSHD and lives with unimaginable pain. I consider myself lucky, as I was only diagnosed in my 50s, but I have declined quite rapidly since.

Kristen: Beyond the extensive management of this disease, it also comes with so many fears that you try not to give into. Fears that my husband and I have. Without help from a therapy that can even slow progression, what will her state be in 10 years? Right now, her organs are healthy but with her slowing down in her ability to move each year will her organs start to be affected, shortening her life? A reality that is real for kids with FSHD.

Q. How do you manage FSHD?

Kristen: Exercise and keeping Kate moving are important, so we have her in physical therapy three times a week and with a personal trainer for a fourth workout. She swims two to three times a week with her Paralympic swim team. It is heartbreaking to watch a child work so hard to only have small gains, stay status quo or lose functionality and not be able to explain to her why. We are just lucky that she has not given up and still is willing to fight the fight with us.

Q. What other accommodations for FSHD have to be considered?

Michele: Everything has to be reconsidered, and the rules change every day as we decline with FSHD. One of the most recent realities for me is that I cannot hold my own grandchild. There is too much risk. This is after I served as a nurse in a neonatal intensive care unit for years, where my responsibility was to care for vulnerable babies – and I cared for them as my own. It does not sound like a major issue, but it’s another example of fundamental joys and experiences I have been robbed of because of this terrible disease.

Kristen: For us, Kate cannot just walk into a school or a camp.?Everything has to be thought out. What does that class do? What buildings are they going to and how do we get Kate there? At the start of every school year we have to meet with the school and make a plan to ensure Kate gets the time needed to transition and all the buildings are ADA compliant. For example, Kate wanted to go to sleep away camp with her best friend this summer. I had to go into deep research and call every camp and discuss our situation and our willingness to help them become ADA compliant. It took 20 camps and many hours of driving to tour the camps to make this dream of hers a reality. Most parents just have to sign their child up online and send their child. Once we had a camp picked, then I had to spend hours researching devices, talking to companies and demo-ing products that could help Kate get around independently and truly take in the camp experience.

Q. Jennifer, growing up with several family members affected with FSHD, what do you remember as a child?

Jennifer: I remember one day playing outside with a younger relative. He tripped and my aunts looked at each other with an expression that shot fear through my body. I knew they were scared but I wasn’t completely aware of what was going on. It’s amazing how one remembers these moments. Five years later was the last time I saw this relative standing, when he was 14 years old.

Q. Michele, how has FSHD affected you and your daughter?

Michele: Gross motor function loss has already taken its toll on all of us as a family. But the loss of simple pleasures sometimes can be even worse. My daughter and I both got rid of most of our summer sandals and flip flops as they can hinder one’s balance and can be dangerous due to foot drop. She loved her purse collection but now even the lightest one is too heavy and uncomfortable to hold. Strolling through a park is difficult and forget about carrying something to eat or drink at the same time. My daughter works with vulnerable ill children. She loves her job. But now she fears she will someday soon have to give it up because this noble career involves talking. The list goes on and on.

Q. Kristen, what does your young daughter know about FSHD?

Kristen: For Kate, she is so good at not thinking about what this could mean but sometimes when it is bed time she will tell me things like, “hey Mom I did not tell you but last night I dreamed I could run and it was so real and felt so good” or “Mom I am so scared of dying and I don’t want to die.” When asking her where that idea comes from, her response is, “I am scared of FSHD sometimes because it’s so hard to know what it is doing to me.” Another question I get from time to time – “Why me?” All things I don’t have answers to or solutions for.

Jennifer: I understand that frustration as a parent, not being able to fix things for your children. And we have to stop this vicious generational cycle. We also hear from the community that adults with parents with FSHD who do not show symptoms won’t get tested. The have seen what their parents have gone through and are not prepared to face their potential fate. On a practical level some adult children fear that having that diagnosis could affect their future ability to secure life insurance or medical coverage. And you know what? Without any disease intervention, what’s the point of getting tested? I’m not even sure what getting tested did for me except to give an awful name to this awful situation.

Q. Jennifer, how has your life changed since your diagnosis?

Jennifer: I am the lucky one in my family. I didn’t realize I had FSHD until I was 50. I began to show symptoms when I was 45. Stairs became a little difficult. Raising from a chair was a tad hard. It’s been seven years since my diagnosis (12 years since I noticed symptoms). I went from living a completely normal life before age 45 to a highly restricted one now. Because I cannot rise from a chair, I cannot go anywhere because toilets (even those that are “ADA compliant”) are too low. The bar on the wall is of no use to me because I don’t have the arm strength to pull myself up. Even one step has become impossible. I can no longer visit any of my friends. You would be surprised how few places there are without one or two steps. Canes and adaptive equipment unfortunately don’t help. Truly though, I consider myself the lucky one in my family.

Q. Kristen, your daughter lives with FSHD. What do you want for her?

Kristen: We are not looking for a silver bullet right now.?We are looking for just help in slowing the progression so her regimen of clean living and exercise can either keep her stable and healthy or allow her hard work to give her a slight edge to gain strength.

Q. What are your hopes for yourself, for your family?

Michele: I will persevere as long as my daughter doesn’t get any worse. My husband’s and my retirement is already severely impacted and I am so sad for him. But the thought of a young woman whose health and future are uncertain makes retirement I guess seem secondary. I’ve lived my life although I’m not that old. But she has everything to look forward to and, yes, she sees joy, but sometimes the fear and grieving for lost mobility are overwhelming.

Jennifer: I live in fear for the future generations of my family. The only solace I have now is the possibility that there will be disease intervention. Of course, a genetically mediated cure is what we all want. However, any chance to stop progression of this disease is as powerful to us as reversing time. Had I been able to stop progression at the time of my diagnosis, I would have a completely normal life now with just a little difficulty getting upstairs or out of a seat.

Q. Anything else to add?

Michele: I am so grateful for all the researchers seeking a treatment for this dreadful disease. The clock is ticking as our mobility quickly declines along with our mental states. I hope and pray there will be something for us soon.

Please link to A Call to Action for specific suggestions in terms of you can do to help!

References

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