Rarest Of The Rare: Two Women Among The Eleven People Reported Worldwide With Rare Genetic Disorder, Myopathic Ehlers-Danlos Syndrome, Seek Awareness For ‘Invisible Illness’Posted February 28, 2018
Oklahoma mother and daughter receive rare disease diagnosis from NIH only to find they are alone with their specific genetic mutation of painful and potentially disabling form of Ehlers-Danlos syndrome.
BALTIMORE, MD USA — When Oklahoma teenager Whitney Silver began experiencing severe joint dislocations and chronic pain in 2013, it only took three months for a rheumatologist to diagnose both her and her mother, Rochelle McLemore, with hypermobile Ehlers-Danlos syndrome (hEDS). Frustratingly, though fortunately, their geneticist was unconvinced by this diagnosis. While he agreed that the mother and daughter likely inherited one of the Ehlers-Danlos syndromes, a group of often-painful, potentially degenerative, genetic disorders affecting connective tissues, the geneticist also observed much greater muscle weakness and atrophy than his other hypermobile Ehlers-Danlos patients. Indeed, the severity of Whitney’s muscular weakness at the cellular level has exacerbated her joint instability to the point that it has caused her femurs and tibias to rotate.
LOST HOPE AND MUSCLES AT THE BREAKING POINT
For Whitney, the breaking point came at a school dance, where she lost control of her legs—and her knees, hips, and ankles wobbled and buckled with every step she took. “It was the really big indicator that something was going on that was beyond EDS hypermobility,” remembers Rochelle.
The intensity of Rochelle’s experience baffled her local physicians. “We even lost some of the doctors that we trusted …they were so overwhelmed with what was happening and they just threw up their hands in shock and frustration.”
Although Rochelle’s muscular symptoms are less extreme than Whitney’s, both of them experience instability, dislocations, incoordination, and constant muscle pain. Rochelle also has cardiomyopathy and digestive symptoms. Whitney has dysautonomia and seizures.
THE RAREST OF THE RARE
Unable to pinpoint their diagnosis, their local geneticist referred their case to the National Institute of Health (NIH) for further testing. Upon completion of a full exome sequencing, the NIH invited them to fly to their Bethesda clinic for follow-up. There, Rochelle and Whitney discovered their cases were among the rarest of the rare. Diagnosed by the NIH with a then-unnamed variant of Ehlers-Danlos syndrome in 2016, there were no established criteria for their particular mutation of EDS. It wasn’t until the 2017 Ehlers-Danlos International Classifications were published that their condition was given a name: myopathic Ehlers-Danlos syndrome.
The mutation for myopathic Ehlers-Danlos syndrome occurs on the gene called COL12A1, altering type XII collagen production primarily found in skeletal muscles.
While medical literature has only documented nine patients in five families with the myopathic form of Ehlers-Danlos syndrome to date, gene sequencing for Rochelle and Whitney uncovered an even rarer discovery: their specific mutation had never been seen before.
“It felt amazing to have a name for my condition,” said Whitney. “The criteria, specifically the muscle atrophy/hypotonia and joint hypermobility, matches us very well, the joint contractures some but not as much. I think a big thing for us is the inability of our tissue to recover and rebound from stress or overuse, which is a HUGE deal for Whitney and to a lesser extent for me. Digestive issues and random tissue pain—pinpoints of random pain all over, not just in joints—are also big,” says Rochelle.
THE IMPACT OF COLLABORATIVE RESEARCH
“It is exciting and rewarding to see the real-world impacts of the updated Ehlers-Danlos classifications published last year by the International Consortium on Ehlers-Danlos and Related Disorders,” says Lara Bloom, international executive director of the Ehlers-Danlos Society. “Since the new criteria increased the number of Ehlers-Danlos syndrome types from 6 to 13, individuals like Rochelle and Whitney are finally able to put a name to the condition that has so heavily impacted their lives.”
“At the same time, the more we learn, the more we need know,” argues Bloom.
The Ehlers-Danlos Society’s physicians concur. More research is necessary.
“It’s entirely possible that the genetic mutations for what we currently diagnose as hypermobile Ehlers-Danlos syndrome might actually code on many different genes—and thus be reflective of a collection of genetically different disorders, rather than one, singular disease. By thoroughly investigating the rarer types, in conjunction with our current plans for mapping hEDS, we will ultimately gain a better understanding of all types,” states Clair Francomano, M.D., chair of The Ehlers-Danlos Society’s Medical and Scientific board, chair of the International Consortium’s Classical EDS committee, and director of Ehlers-Danlos Society Center for Clinical Care and Research at The Harvey Institute of Human Genetics of the Greater Baltimore Medical Center (GBMC), whose work includes the co-founding a genetic research network devoted to the genomic mapping of hEDS.
FROM DIAGNOSIS TO ACTIVISM
“It is weird. We share so much with the rest of the EDS community, the same struggles and emotions,” says Rochelle. “At the same time, at least for me, when I am around my fellow EDSers I still feel somewhat different. Sometimes it almost feels like there are some aspects of me that no one — EDS related or otherwise — will understand. That feeling was there even before we got the whole exome sequencing results. At times it is very overwhelming.”
For Whitney, “What makes this condition worse for me is that we appear normal. We don’t need people making rude comments when we park in the handicap spot. Just because we look okay, doesn’t mean we are okay. It’s very irritating when older adults tell me I’m far too young to feel this way or even know what real pain is. Trust me when I say, we don’t want to feel this way, but this condition doesn’t play by our rules. We want to be normal. We just aren’t.”
To resolve this struggle, greater awareness is necessary—and mother and daughter refuse to be slighted, becoming passionate Ehlers-Danlos advocates shortly after their original diagnosis through active involvement with the local Oklahoma Ehlers-Danlos group, EDSOK. Rochelle is now one of the leaders of that group. In 2013, Rochelle worked with State Representative Ed Cannaday to write a proclamation naming May as Ehlers-Danlos Awareness Month in the state of Oklahoma. EDSOK reauthorizes that proclamation every year with an awareness day at the State Capitol where they speak to politicians and visitors about the Ehlers-Danlos syndromes.
Rochelle was also recently named a Patient Expert on the International Consortium for Ehlers-Danlos Syndromes and Related Disorders.
“I will never forget the reaction of my primary care doctor that had stood by me for over 20 years. When I told him that I had been diagnosed with EDS along with Whitney, he said, ‘Wow, I always knew there was something going on with you that was outside of the norm, but I would have never come to this conclusion.’ We need to change that. Awareness needs to start at the most basic level….our primary doctors, the ones who know us best. Our local group is launching grassroots efforts to get that word out to physicians. They need to understand that we are very real. We are more than a brief mention in medical school. To the world, we may be rare — to us, this is 100% real life.”
Whitney, now 19, is following in her mother’s footsteps as an EDS advocate. She hopes the story of her rare diagnosis can help others. “I firmly believe that for those of us with EDS to be able to advocate for ourselves we must know the driving force behind our condition. Knowledge is power. The discovery of the genetic root causes of the different types of EDS is key. We may be rare, but out of our rareness comes my hope that our story can be used to further that research.“
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