Over 4 decades of Compassionate Care and State-of-the-Art Technology
Think about the impact of genetics on today’s healthcare. You can hardly go a day without seeing news of a novel gene for a common disease or a clinical trial for a genetic disorder. Now think back to 1974 (or imagine it, if you’re under 35 J). Back then, genetics was little more than a minor medical sub-specialty, diagnosing diseases few had heard of, and with little hope for treatments or cures.
The Greenwood Genetic Center (GGC) opened its doors in 1974,under the leadership of two visionary co-founders, Roger Stevenson, MD and Hal Taylor, PhD, and with two guiding principles – offer the best most compassionate care and provide state-of-the-art technology. GGC began with support from the South Carolina Department of Disabilities and Special Needs, who in 1974 had the vision that in order to prevent or treat disabilities, they must be understood. They realized, even back then, that genetics was going to provide that understanding.
Now, 43 years later, GGC still operates under those founding principles of compassion and innovation, and we still ardently work to diagnose patients with both ultra-rare and common complex disorders, but what has changed are the dramatic advances in the field of genetics led by our scientists and colleagues around the world.
Hundreds of patients each year are served by our metabolic genetics treatment program, offering proven therapies to treat or prevent serious disabilities and health issues.
Every single year, seventy babies in South Carolina are born free of birth defects of the brain and spine thanks to GGC’s Birth Defect Prevention Program.
GGC’s commitment to providing hope for families impacted by genetic disorders has led to the creation of the Center for Translational Research, which is leading the way in developing clinical trials.
Researchers at GGC are working to fundamentally transform the diagnosis of autism with the development of a blood-based test and work toward treatment trials.
GGC’s Division of Education provides outreach genetic education to students from middle school through post-graduate training, encouraging students to pursue careers in the sought-after and highly rewarding field of medical genetics.
In 1974, few people would have imagined the fundamental changes in medicine that would occur thanks to the field of genetics. Dr. Stevenson and Dr. Taylor imagined it. The South Carolina Department of Disabilities and Special Needs imagined it. And because of them, two generations have now benefitted from compassionate clinical care, enhanced diagnostic testing, cutting-edge research, and innovative educational programs.
The Gene Scene will share the stories of families, scientists, and innovations that have made these past 43 years so exciting, so rewarding, and so impactful, and are making the future so promising. Welcome to The Gene Scene.
After struggling for years to have a child, Greenville’s Wes and Brooks Connor were elated when little Charlie was born – ten fingers, ten toes, the picture of health. That bliss was short-lived when they learned that Charlie’s newborn screen, commonly called the heel prick test, came back positive. Charlie, who will turn eight in April, was diagnosed with isovaleric academia at five days of age. At the time of his diagnosis, he was the only child in SC with this condition.
Isovaleric academia (IVA) is a rare genetic disorder in which the body is unable to break down a certain component of protein called leucine. If left untreated, it can lead to vomiting, seizures, coma, and even death.
“Fortunately, Charlie’s course has been mild and by altering his diet, his IVA has been well controlled,” shared Brooks.
Charlie is followed by Dr. Neena Champaigne through the Greenville office of the Greenwood Genetic Center. “IVA is a recessive condition meaning that while both of his parents are unaffected, they each carry the altered gene,” said Champaigne. “Charlie has been doing well with treatment which includes a low protein diet and supplements.”
“The Greenwood Genetic Center, particularly Dr. Champaigne, has been there for us since we got that first frightening phone call nearly eight years ago,” said Brooks. “I don’t know where we’d be without them, but I do know, even though this disorder is very rare, that we are not alone in this.”
To support other families with genetic disorders and to show their appreciation for the team that cares for Charlie, “Charlie’s Angels” as Brooks calls them, the Connor family hosted last weekend’s 3rd annual Race the Helix – Upstate.
Participants including GGC employees, families, competitive runners, and others who just wanted to do something worthwhile with their Saturday morning, enjoyed a hilly 5K trail run or a nice leisurely 1 mile stroll, all to provide support for families like Charlie’s. Proceeds support the GGC Foundation which provides services for families who are unable to afford them, as well as support for diagnostic testing, research and educational programs of the Center
With five offices across SC, the GGC Foundation is working to develop events and support in all five of those areas. Race the Helix-Greenwood is planning for its 7th year, the first ever LowCountry race will be in Charleston on May 6th. Events in Columbia and the Pee Dee are under development.
The story of the Shenal family, who started the first Race the Helix in 2011 was in an earlier Gene Scene post.
When you think about genetic research, the first things that probably pop into your mind are lab benches, white coats, sterile environments, and rigid protocols: a very cold and aseptic atmosphere. Well, you won’t find any of this in the story you are about to read. This, instead, is a story about bringing the genetics outside the lab and connecting with the people who need it more than anyone else: patients and their parents.
It all began almost 30 years ago when Drs. Katy Phelan, Curtis Rogers, and Robert Saul from the Greenwood Genetic Center (GGC) described a patient with a loss of genetic material on the long portion of chromosome 22, first as a poster presentation the American Society of Human Genetics meeting in 1988, then in a paper published in the American Journal of Medical Genetics in 1992. In simple words, they reported a new genetic condition, caused by the loss of several neighbor genes, and characterized by delay in reaching the developmental milestones and other feature that we will explore later. At that time, the technology was more rudimentary than today, therefore the possibility of detecting losses of genetic material was limited to relatively large deletions, spanning for several millions of nucleotides (the building units of our DNA). However, once the new condition was first described, new reports followed with similar cases, including one from Dr. Heather McDermid and her collaborators from the University of Alberta, so the name Phelan-McDermid syndrome (PMS) was eventually designated by parents of those diagnosed with PMS to indicate this novel entity.
So far the story is not much different from any other discovery in the genetic field, but here is where the unique part begins. The possibility to look for the abnormality on chromosome 22 brought a molecular answer to several families that had received different clinical diagnoses, from cerebral palsy to intellectual disability with multiple congenital anomalies. Now, they had to face this new syndrome, so they turned to the people that first described the syndrome, Katy Phelan and Curtis Rogers. And the two doctors answered the call. Actually, multiple calls, so frequent that Dr. Phelan started to call “telephone buddies” the members of the first 15 families that got in contact with her. That was the beginning of an extraordinary collaboration between GGC and the families of the patients with PMS, a collaboration later cemented by the presence of Drs. Phelan and Rogers in the Board of Directors of the Phelan-McDermid Syndrome Foundation (PMSF), as Founder and Chairman Emeritus, respectively.
Several years after the original paper, the phone calls led to the First Support Group meeting in Greenville, SC (see photo), realized with the help of GGC and the Mikel Foundation, then the first informational website on PMS was launched (2001), and the Foundation was established (2002). The detailed history can be found on the PMSF website (http://22q13.org/j15/), along with lists of events and ways to support the Foundation, and the link to the Phelan-McDermid Syndrome International Registry, an exceptional tool for physicians and researchers involved in PMS.
The collaboration between GGC and the families with PMS was not just limited to the pure diagnosis: during the biennial meetings the team from GGC collected blood samples and clinical information, the parents were able to meet the people working on the syndrome, ask their questions and share their concerns. Physicians and researchers provided their knowledge and expertise and received in return an incredible amount of positive energy and motivation. The families, caught in the daily struggle with the genetic disorder, were able to -share their experiences with other families and with the medical experts. It is somehow reassuring, if your child has just received a diagnosis of a rare genetic syndrome, to be able to talk with another parent who is facing the same challenges and, at the same time, to be pointed towards a doctor who regularly sees dozens of similar cases.
But, what are those challenges? Why is it so important to keep such a strong channel of communication between families and physicians? PMS is not exactly a typical genetic syndrome: first of all, the patients may present with a wide array of symptoms. The most common features reported in PMS cases include intellectual disability of several degrees, impaired speech that can range from no words to few sentences or even normal language skills, and low muscle tone, especially at birth. Other common traits include behavioral issues, from simple irritability to autism, seizures, reported in 1 out of 3-4 patients, and other neurological symptoms, such as abnormal reflexes or impaired regulation of the body temperature.
Considering such high variability, it is not surprising that collecting detailed clinical information and being able to keep a schedule of regular follow up evaluations is critical for the physicians to manage the symptoms and provide the best information possible to the families.
If things were not complicated enough, the clinical variability is matched by an equally high genetic variability. Unlike the vast majority of conditions caused by genetic deletions, PMS does not have recurrent breakpoints, therefore the amount of lost genetic material is different in each individuals and can range from about 100,000 to over 9 million nucleotides. To use a simple analogy, typical deletion syndromes occur due to misalignment of certain DNA sequences (named copy number variants, or CNVs) that are present in high numbers in our genome, are highly replicated and interspersed randomly through the chromosomes. Imagine that the two chromosomes in a pair are getting together just as you wear a buttoned-down shirt: the buttons get in the holes just like the CNVs pair with their counterparts on the twin chromosome. Now picture yourself on a busy morning: you are trying to button up your shirt in a hurry and you skip a button, you put it in the wrong hole and you create a loop, which starts with the last button correctly aligned and ends with the next one that gets in the hole. With chromosomes, when a button (CNV) “skips” an alignment, the resulting loop gets cut off and the genetic material in that portion of chromosome is lost. This is what happens in typical deletion syndromes. But PMS, remember, is not quite typical and instead of buttons uses a zipper. When you have a misalignment with a zipper, you have no clue of how many teeth you might have skipped, and you don’t know where the resulting loop begins and where it ends. Similarly, in patients with PMS, the deletions on chromosome 22 do not seem to have a designated start or breakpoint (indicating the point where the chromosome “breaks”), although almost all cases involve the end of the long arm portion of the chromosome, hence the adjective “terminal”.
And finally, to make things even more confusing, there are cases of PMS in which chromosome 22 is intact, but there is a change in the sequence of one of the genes usually involved in the deletions, named SHANK3.
It is easy to understand how, even after 25 years from its first report, PMS still poses numerous challenges, both in the clinical and molecular fields. In order to answer these challenges, GGC has contributed a significant effort through the years and is still proud to work side by side with the PMSF, presenting the results of such efforts to their meetings (see photos), continuing to provide clinical and counseling services, and proposing new research projects focused on better understanding the mechanisms underlying PMS and giving to the families new insights and eventually the possibility of treatment. The story is still going, and it is up to physicians and parents to write the next chapters, together like it has been in the last three decades.
Autism is the third most common developmental disability. An estimated 1 in 68 kids has been diagnosed with autism, and their numbers are growing. Yet its origins remain elusive. Consequently, so do effective treatments.
The science behind autism has been obscured by misinformation, misunderstanding of the disability itself, and the sheer complexity of autism research, therapy, and treatment. Recently, scientists working in autism research have focused their studies on genetic links and biochemical disruptions that impact brain development and brain function.
As part of that focus, researchers at the Greenwood Genetic Center (GGC), along with collaborators from Biolog, Inc. in California, found that people with with autism spectrum disorders (ASDs) showed significantly decreased metabolism of the amino acid L-tryptophan when compared with control groups.
L-tryptophan is one of nine essential amino acids. These amino acids are called essential because they cannot be made by the human body but must be obtained through diet.
Tryptophan is the precursor of key neurochemicals such as serotonin and melatonin, which help the body manage sleep, control moods, and even hold depression at bay.
GGC’s scientists learned that cells from individuals with autism metabolized L-tryptophan at a decreased rate, while cells from individuals without autism did not show this change.
Researchers also measured the expression of genes — the process by which genes produce the structure of a cell. Specifically, our researchers examined those genes that are known to be involved in L-tryptophan metabolism in a small subset of patients with autism. They found these patients also expressed some of the genes at lower levels than those without autism.
“The important and immediate implication of this work is the development of a simple, early blood-screening test for autism by measuring the metabolism of L-tryptophan using Biolog’s technology,” shared Dr. Luigi Boccuto, staff scientist at GGC.
Currently there are no laboratory tests that can accurately diagnose autism; therefore, diagnosis depends upon a developmental evaluation and parent interviews. This prolongs the diagnostic process, and it means that many children are not diagnosed until they are 2 or even 3 years old. The window to intervene early is nearly closed before a diagnosis is even made.
When Parker, Laura’s son, was 18 months old, she became seriously concerned about his development. “He had frequent tantrums because we couldn’t communicate, even through pointing, and we couldn’t understand what he needed. It was like playing a constant never-ending game of charades, she said. “Parker’s diagnosis was a long, drawn-out journey.” Within six months, Laura knew the likely diagnosis, but it took another two years to get in to see a developmental pediatrician and start the initial testing. The testing itself was a six-month process.
“A screening, and eventually, a diagnostic blood test for autism would be of immense value to families,” explained Dr. Charles Schwartz, director of research at Greenwood Genetic Center and lead investigator. “An early, accurate diagnosis is key to providing effective and timely therapies for these patients and their families.”
Dr. Boccuto added, “We also see tremendous potential that these findings will aid in our understanding of the … bases of autism. Once we have a clear vision of what has gone awry within the tryptophan metabolism pathways, we can develop therapies to target and correct those problems at the research at Greenwood Genetic Center and lead investigator. “An early, accurate diagnosis is key to providing effective and timely therapies for these patients and their families.”
Dr. Boccuto added, “We also see tremendous potential that these findings will aid in our understanding of the … bases of autism. Once we have a clear vision of what has gone awry within the tryptophan metabolism pathways, we can develop therapies to target and correct those problems at the biochemical level.”
“Your baby will likely be incompatible with life.” “Her heart won’t manage to beat on its own.” “Your body is doing all the work of surviving for her.” These words swiftly knocked the breath out of me, as I sat clutching my husband’s hand in disbelief. I was eight months pregnant and had just received a 4D Ultrasound to check for possible growth restrictions. Unexpected, unfathomable words from a doctor broke our hearts and rendered us completely shattered and alone that day.
We were still reeling from our six year old son’s recent diagnosis of Asperger’s Syndrome. Just as we were beginning to process a world of information on Asperger’s, and searching for ways to make his life easier, this new curve ball came at us out of the blue. Learning that our unborn daughter likely had a lethal genetic disorder, and appeared to have multiple anomalies (including defects affecting her brain and heart) was a devastating shock.
Amniocentesis quickly followed and then there were days of gut wrenching waiting. We opted to have a FISH test completed, to see if our unborn baby girl had a genetic disorder that would likely rob her of life. My husband and I were not afraid of her having disabilities – we could handle that. We just needed HOPE; we needed to know that she would have a chance at LIFE. After a long weekend of merely surviving ourselves and trying to maintain composure in front of our son, the FISH test results were in. Thankfully, the test ruled out the terrifying disorders that we all feared. We knew we still had weeks of worry and careful monitoring ahead, but we were grateful. We had no guarantees or definitive answers at that point, but we had a shot at life. That’s all we needed.
After weeks of monitoring her tiny heart and restricted growth, our beautiful 4lb, 1 oz baby arrived. Words can’t express how it felt to hear the first cries of a child we had feared of losing. Our beautiful Ryleigh Cathrynne was here with us and we were over the moon! She was whisked away quickly to the NICU, where she’d stay for three long weeks. The defects of her heart and brain were to be monitored, but did not appear to be life threatening as once believed. In the early hours of our hospital stay, we were introduced to a wonderful, compassionate doctor from the Greenwood Genetic Center. I remember his warmth in explaining testing that would be done on her cord blood to rule out rare genetic disorders affecting segments of chromosomes. While we genuinely appreciated his caring, personable demeanor and his thorough examination of our baby, any thoughts of genetics and chromosomes exited my hospital room with him.
After a few weeks, Dr. Skinner called me at home to personally deliver the results of the in-depth genetic testing that was done. Ryleigh was diagnosed with a rare genetic disorder, a Chromosome 1q43q44 deletion. The conversation was a blur as I tried to breathe and to refrain from crying. I was terrified with the unknown and what this all meant for my child. With warmth and sincerity in his voice, he delivered a reminder that has remained with me from that moment forward. “Ryleigh is still the same beautiful baby she was before we had this conversation.”
In discovering that our daughter would face a life of challenges, limited independence and disabilities that no one would be able to fully predict, we experienced tremendous grief. We had come so far and now worried what obstacles the future would present to her. Gratefully, as our family started down this new path of life, Dr. Skinner and everyone we encountered at GGC helped us find HOPE.
After our first consultation at GGC with Dr. Skinner and our Genetic Counselor, Lauren McNair Baggett, my husband and I knew we were in the best of hands. We were in a place of compassion and first rate care. They gave us an abundance of resources and referrals to immediately begin early intervention. We began to realize that WE WERE NOT ALONE. As our new life unfolded, we felt compelled to somehow give back to this amazing place and to use our experience to help other families in our shoes. We wanted to raise awareness, both for GGC and for other families facing a genetic disorder diagnosis. With the help of GGC’s Dr. Mike Friez and a team of dedicated volunteers, our first Race the Helix 5k and 1 mile run/walk fundraiser event was born in October 2011!
Fast forward nearly six years…We are blessed beyond measure that GGC and our community has embraced Race the Helix. We are very proud and astonished of the national and global support it has gained. With the help of many committed volunteers and generous sponsors, Race the Helix has grown and expanded beyond anything we could have ever imagined. Our family has been impacted by an Autism Spectrum diagnosis and also a rare genetic diagnosis. GGC has been there for us all along the way. It is for these reasons we are continuously driven to support the mission of GGC and to help families find hope as we did.
How many times as a child were you asked ‘What do you want to be when you grow up?’ What was your answer? Maybe an astronaut or a movie star? Did you ever consider molecular geneticist, genetic counselor, or bioinformaticist? Interest in these high tech, in-demand careers are precisely what GGC’s Division of Education hopes to achieve through various student outreach programs.
There is and will continue to be a need for educated and highly skilled workers in science and technology. But how do you engage younger students and introduce them to the field of biotechnology with the hope they will pursue careers in the life sciences?
GGC’s most successful educational outreach program has been the Gene Machine, our mobile science lab. By traveling to middle and high schools throughout the state, the Gene Machine provides hands-on educational lab experiences to students.
Why is this important?
Well, unfortunately, not all students have equal exposure and access to equipment and technology in science. The Gene Machine, and our on-campus Genetic Education Center helps to equalize access, making these resources available to all students regardless of their geographical locations.
In the first 6 years of these programs, we have worked with over 31,000 students, and regularly receive amazing feedback such as:
‘You shared a lot of great information about the science of genetics and careers in the genetics field. I know you inspired at least one of my students today to pursue a career in genetics. As we left the lab tour he told me, “I can do that job”…such a powerful thing for a student to realize and believe.’
‘My students’ experience on The Gene Machine was phenomenal! It is still the #1 best way to engage students in science. It is the best thing that I can get my students to look forward to every year and the results are always superior to the experience.’
We’re seeing positive results like these everyday, but what do we do with these students when they choose a career path in biotechnology? Well, we offer high school students shadow days to see what a day in the lab is like. We provide summer internships for college students to gain real-world experience and possibly even a publication for their resume. Then, once they have their PhD or MD, they can join GGC’s Medical Genetics Training Program for post-doctoral students and residents.
Education was one of the primary objectives when the GGC was formed back in 1974, and today it remains a top priority. Through advanced educational technology we are reaching more students and teachers than ever.
But there is work yet to accomplish! Keep in touch and watch us grow!
For more information, contact Dr. Leta Tribble email@example.com
We all learned about Gregor Mendel and his pea plants in middle and high school, and who could forget those Punnett Squares? Dominant and recessive, chromosomes and the double helix, these concepts were so interesting in biology class (at least to me), but what happens when they become more than abstract concepts and vocabulary words? When they become real and personal? What happens when it’s your child who is struggling and diagnosed with a rare disease?
In the genetics clinic, we work with families everyday for whom these concepts aren’t just things to learn for a test – they are real and they are scary. We can share information, educate them on where that extra chromosome came from or what’s the chance that this condition will recur in the family. And patients need that information, but they need something else even more – hope.
Hope – that despite everything you may have read online, your child is not a list of symptoms, is not defined only by their diagnosis, but he or she is an individual and that we will do everything on our power to support and encourage their health and development.
Hope – that someone, somewhere is researching this disorder, no matter how rare, and that progress can be made.
Hope – that even though you may be the only family in Greenwood, or even in South Carolina with this diagnosis, you are not alone.
Through careful clinical evaluations and compassionate genetic counseling, our goal with all of our patients is to educate, inform, and support, but taking it a step farther, we want to make sure they leave our clinic with a renewed sense of hope that someone is there for them – someone cares.
Through the Greenwood Genetic Center’s five clinical locations across South Carolina, along with a new telehealth initiative, we strive to ensure that if you need our services, if you are seeking to find that hope, you can connect with us.
If you’re planning a pregnancy, but are fearful of your family history; if your son or daughter isn’t hitting their milestones as expected, if there is cancer rampant in your family and you’re afraid of being next – you are not alone.
Information, support and hope are available, you just have to reach out and take it.