Gene Therapy

Response To Clinical And Genetic Aspects Of Ehlers-Danlos Syndrome, Classic Type

I read with interest the review of the clinical and genetic aspects of Ehlers-Danlos syndrome (EDS) by Malfait et al.1 This otherwise excellent review was weakened by the cursory discussion of pain associated with EDS. The authors do not include assessment and characterization of pain in the recommendations for initial evaluation, and pain is only briefly mentioned in management of musculoskeletal manifestations (Anti-inflammatory drugs may help with joint pain), prevention of musculoskeletal manifestations (Individuals with muscle hypotonia and joint instability with chronic pain may have to adjust lifestyle and professional choices accordingly), and under emotional support (Emotional support and behavioral and psychological therapy may be indicated to accept and cope…with the long-term chronic pain).

Chronic pain has long been recognized as a clinically important manifestation in all types of EDS.2,3 The pain is severe, unremitting, and significantly impacts activities of daily living, sleep, energy levels, and quality of life.3–5 More recently, systematic study of pain in EDS has better characterized the contribution of clinical factors to pain in these patients.3 Dislocations, joint hypermobility, and previous surgery in ascending order of importance were significantly associated with pain.3 Despite these studies, the actual cause of the pain in EDS remains unknown. The patients with EDS followed through my clinic have generally had extensive (and expensive) evaluations including batteries of rheumatologic tests and many imaging studies. Most have been on multiple pain medications, both over the counter and prescription including narcotics, with poor results. They uniformly express frustration as their providers are unfamiliar with EDS and are unaware of the chronic pain associated with the diagnosis. This coupled with the lack of objective findings of joint inflammation or degeneration results in the patients being labeled as hypochondriacs or drug seekers. Referring these patients to multidisciplinary pain clinics and educating the providers at these clinics about EDS and the pain associated with it has resulted in objective improvement in patient's day to day ability to function and subjective improvement in coping and mood. Medication use is generally less and is safer.

To date, no studies have evaluated the relative effectiveness of pain management strategies in EDS. Multidisciplinary pain clinics are considered the standard of care for management of patients with chronic, complex pain.6 I think that all patients with EDS should be asked about pain as a routine part of the initial evaluation. All patients with pain that requires regular medication, that interferes with activities of daily living or sleep, or that is identified as affecting quality of life should be referred to a multidisciplinary pain clinic for evaluation and treatment. Furthermore, medical geneticists are obliged to educate the pain clinic about EDS and the pain associated with it. Our lack of understanding of the mechanism of the pain should provide the impetus for more research in this area with the hope that improved treatment would follow.

Heritable Disorders Of Connective Tissue Research

Content

Classical Ehlers-Danlos syndrome (cEDS)

Classical Ehlers-Danlos syndrome (previously known as EDS type I/II) is an inheritable connective tissue disorder that involves skin, tendons, ligaments, and, in some cases, also blood vessels. Most cases are caused by mutations in the genes encoding for the subunits composing type V collagen, an essential component of the extracellular matrix in many of the connective tissues in the body. Individuals with classical EDS usually present with hyperextensible skin and atrophic scars and hypermobile joints.

Hypermobile Ehlers-Danlos syndrome 

Hypermobile Ehlers-Danlos syndrome (also known as Ehlers-Danlos syndrome type III) is an inheritable connective tissue disorder involving mainly the joints with hypermobile joints and chronic musculoskeletal pain. Associated extra skeletal symptoms might involve multiple systems including autonomic dysfunction with postural orthostatic tachycardia syndrome (POTS), gastrointestinal problems, and more. The genetic cause for this condition is unknown and the biological processes driving the clinical symptoms in this syndrome are poorly understood. For these reasons, the diagnosis of this condition is based only on clinical evaluation at this time.

Paralympian Grace Nuhfer Missing Start Of Senior Year Of College, But She Has A Pretty Good Excuse

"Apologies for not being in class. I swear I have a good excuse."

That's the email Grace Nuhfer plans to send to her college professors at the University of Akron, she said as she sat with a Paralympic silver medal draped around her neck.

The 22-year-old is entering her senior year at Akron, where she's majoring in data analytics with a focus in marketing and is a member of the non-para swimming team.

The semester has already begun, so Nuhfer will have some catching up to do once she returns home from Paris, but she wouldn't have it any other way.

Just a year after making a splash in her para swimming debut at the California Classic — where she swept all six of her events and set an S13 American record in the 200m butterfly — Nuhfer not only made her Paralympic debut, but won the silver medal in her first event (100m butterfly).

It's a moment she has been visualizing and perhaps manifesting since the Paralympic medals were unveiled earlier this year

"I actually had someone at my school help me print out an image of the Paralympic medals and I had it taped in my locker so I looked at a picture of the medals every day going into training," Nuhfer said. 

Nuhfer and her sister Elaina both have Ehlers-Danlos syndrome, a group of genetic connective tissue disorders that affect the skin, joints and blood vessels. They also have brittle cornea syndrome, a rare genetic disorder that impacts their vision and makes their corneas prone to rupturing.

"Growing up my sister and I weren't allowed to play any sports with balls, bats or rackets because the nature of our genetic disorder makes our eyes extremely fragile," Nuhfer said. "We tried running, we tried dancing but (having) Ehlers-Danlos also just made things hard and painful, so swimming was kind of the only option left, but I'm really grateful I fell in love with it."

Nuhfer began swimming competitively when she was 7 years old and always had big dreams.

"Growing up swimming able-bodied, it was always a really big dream of mine to make the Olympics," Nuhfer said. "Once I started growing into the para space and realized where I stood and what possibilities were out there, (the Paralympics) became a really big goal of mine."

When Nuhfer is swimming, her vision prohibits her from seeing anything aside from the black line at the bottom of the pool. Throughout her career — spanning from club competitions to college meets and the Paralympics — Nuhfer attributes her success in the water to the unwavering support of her teammates.

"Everyone has been super helpful and made sure that I knew what was going on or helped me with sets or intervals or looking at the clock, which has been really sweet," Nuhfer said.

Nuhfer's debut Paralympics are not done just yet.

She is scheduled to compete in two more events in Paris: the 50m freestyle on Sept. 2 and the 200 individual medley on Sept. 3.

"I have a lot of amazing teammates in the S13 classification who are going to be going through these events with me, so I'm just excited to have these moments with them and whatever the outcome … if an S13 American is on the podium — no matter who it is — I'm going to be completely ecstatic."

Then it's back to Akron to get her senior year underway. And of course the silver medal is coming to campus with her.

"I definitely want to show my teammates (the medal) because they're a big reason as to why it's around my neck right now."

Four-time Paralympian Rose Hollermann used a life-changing moment as motivation and inspiration to get to the top of her sport in wheelchair basketball where she will be competing at the 2024 Paris Paralympics.

---