When Jen Wells-Dickerson was 29, her father was diagnosed with facioscapulohumeral muscular dystrophy (FSHD), a rare genetic disease that causes muscles in the face, shoulders, upper arms, hips, pelvic girdle, and hamstrings to shrink and weaken. Five years later, she began experiencing shoulder pain and debilitating fatigue and had trouble raising her arms. At first she blamed it on too much exercise, but when her primary care doctor referred her to a neurologist, she suspected FSHD. “I knew I had a 50-50 chance of developing it,” she says. “When my shoulder problem wouldn't get better, it was clear that I was experiencing some of what my dad had gone through.” That prompted her to undergo genetic testing, which confirmed the diagnosis.

Now 44, Wells-Dickerson lives in Hamlin, NY, with her husband and two teenage daughters and works part-time in an office. She can still walk, although the former college runner and triathlete can't participate in sports as she once could. The disease affects her ability to smile and use her arms and is beginning to cause her left foot to drop when she walks. That development is especially concerning because when her father began having trouble lifting the front part of his foot, it was the beginning of a more serious progression. Wells-Dickerson has scaled back many aspects of her life due to physical challenges and fatigue. “I'm not as socially active as I used to be, and my husband goes to my daughters’ soccer tournaments because I can't handle it physically.”

Bruce Hermesch, 59, first noticed signs of FSHD in 1992. He and one of his brothers had taken over the family dairy farm in Seneca, KS, and he began to have trouble lifting things and found the labor too taxing. When it became harder to move, Hermesch went to see a neurologist in Ames, who referred him to a specialist at Mayo Clinic in Rochester, MN. “That doctor took one look at my chest and pecs and said my underdeveloped muscles meant I either had FSHD or limb-girdle muscular dystrophy.” Hermesch's diagnosis wasn't confirmed until genetic testing became available around 2002. He continued to work on the farm for another eight years, then bought a convenience store, which he operated until it became too physically difficult. He now works as a dispatcher in a sheriff's office.

Genetic Clues

Researchers now have a much better understanding than before of the genetic underpinnings of the disease. They know it's caused by the abnormal expression of the double homeobox 4 (DUX4) gene, which is turned off in people who don't have the condition. DUX4 activation leads to the production of a toxic protein that disrupts normal muscle function, resulting in symptoms associated with the disease. People without FSHD have a sequence of 10 or more copies of the DUX4 gene. When the number of DUX4 genes is between one and 10, the gene is activated, causing damage to muscles. The fewer DUX4 copies people with FSHD have, the more severe the disease is likely to be, says Rabi Tawil, MD, FAAN, endowed professor of neurology, pathology, and laboratory medicine at the University of Rochester in New York. “People with one to three copies are most likely to get FSHD in childhood. If they have four to seven, they might get it in their teens or later. People with eight to 10 copies tend to get it in adulthood.”

Hermesch is the first person in his family—he has eight siblings and 15 aunts and uncles—to be diagnosed with the disease, which means it was likely caused by a spontaneous mutation of the DUX4 gene.

Unlike other dystrophies, most of which follow an almost identical pattern of progression, FSHD can manifest in many different ways, says Dr. Tawil. Some people experience only mild shoulder pain, and others eventually need a wheelchair. “Typically, the younger a person is at diagnosis, the more severe the disease will eventually become,” says Dr. Tawil.

Adapting to Change

The lack of drugs to treat FSHD means that doctors do everything they can to keep patients as functional as possible, says Dr. Tawil. That includes physical therapy, specific exercises for foot drop, and even surgery in some cases. For example, patients whose shoulder muscles are so weak they can't keep their shoulder blades in place may undergo scapular fixation surgery. However, Dr. Tawil says, it's a serious procedure that can reduce lung capacity, so it should be considered carefully beforehand.

Wells-Dickerson and Hermesch both do physical therapy, and Wells-Dickerson found a therapist who was willing to learn about FSHD. “My therapist had never heard of FSHD, so I educated him and asked him to research it so he would know whether what I'm dealing with is related to the disease. I wanted him to know what my limits were and to ensure that I didn't injure myself during a session.”

In the 20 years he's been working as a dispatcher, Hermesch has continually adjusted to the limitations of his disease. When he started his job, he could walk in and out of the office. He used a cane for a while and then began riding a four-wheeled scooter into the building, but then walking everywhere except up and down stairs. Now he is almost always in a wheelchair. He also has trouble with his hands, back, and shoulders. “FSHD affects everything for me. It's asymmetrical and all over the place.”

Hermesch lives mostly independently, except for an aide who comes to his house every morning to help him dress and twice a week to help him shower. He recently had to stop driving his equipped van. Now he rides his wheelchair the half mile to work four days a week and relies on friends and family to help him get to the office on days when the weather is severe. Working is not easy, he says, but it gives him a sense of self-worth and a reason to get up each morning.

There was a time when Hermesch struggled to come to grips with his physical limitations, but he approaches life differently now. “It's been humbling to go from where I was 20 years ago to where I am today. But I've always been outgoing and willing to help others, and I'm not afraid to ask for help now. There are good people everywhere.”

Wells-Dickerson says her husband has been a huge source of support. “He goes with me to appointments to be an advocate but also to learn how things might progress. And he's really good about helping me temper expectations of myself when I feel fatigued and can't check every item off my list.” When she worries about the future, she focuses on how to adapt her surroundings should the need arise. “I'm a big gardener, so I think a lot about how I can set things up so I can still garden if I'm in a wheelchair or can't work with my arms. To me, it's common sense to be realistic about what the future might hold.” She also tries to keep things in perspective. “There are people who need a lot more care and assistance than I do.”

Until a treatment is readily available, Wells-Dickerson says, she will remain optimistic. “Many diseases didn't have treatments 20 years ago, and now they do,” she notes. “Maybe 20 years from now, there will be a treatment for FSHD. For the time being, I'll continue doing all the things I want to do as best I can.”

Ongoing Research into FSHD

At least 10 companies are investigating drugs that may reduce the expression of DUX4, a gene that when activated produces a toxic protein that disrupts normal muscle function and triggers symptoms of facioscapulohumeral muscular dystrophy (FSHD), a rare disorder that causes muscle weakness.

Two trials are actively recruiting adult patients with FSHD. The phase 1/2 FORTITUDE trial, conducted by Avidity Biosciences, is studying AOC 1020, an RNA therapeutic (a drug that uses RNA-based molecules to modify biological pathways to treat or cure disease). A phase 1 study, sponsored by Arrowhead Pharmaceuticals, is investigating a drug called ARO-DUX4. Both trials are evaluating the drugs’ safety, side effects, and effectiveness.

Resources for People with FSHD

• FSHD Muscular Dystrophy Support
• FSHD Society; 781-301-6060
• Living with FSHD
• National Organization for Rare Disorders; 617-249-7300