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.
When you think genetics, what’s the first condition that comes to mind? It may be a chromosomal disorder like Down syndrome or a single gene condition such as sickle cell disease. But as the fields of genetics and genomics grow, we are learning more and more about more common disorders, many of which are adult-onset conditions, and how genetics plays a role. One of those conditions is pulmonary fibrosis.
Julie Jones, PhD, of GGC’s DNA Diagnostic Laboratory recently had the opportunity to attend the Pulmonary Fibrosis Foundation (PFF) Summit in Nashville with nearly 900 patients, caregivers, clinicians and researchers. Below is her experience interacting with this population of patients and families who have more recently come to the attention of geneticists…
What is Pulmonary Fibrosis?
Pulmonary fibrosis (PF) – not to be confused with cystic fibrosis, a very different hereditary lung disease that presents in infancy – is a chronic and progressive lung disease that affects 200,000 Americans and causes more than 40,000 deaths each year. Fifty-thousand new cases are diagnosed annually. There is no known cure, and from the time of diagnosis the average life expectancy is 3 to 5 years. Symptoms of PF may include dry cough, shortness of breath, discomfort in the chest, fatigue and weakness, and unexplained weight loss.
Pulmonary fibrosis is part of a family of related disorders called interstitial lung diseases. In PF, scar tissue builds up in the walls of the air sacs of the lungs, and eventually the scar tissue makes it difficult for oxygen to get to the blood resulting in shortness of breath. As the disease progresses, patients may require supplemental oxygen to breathe. Ultimately, the continual irreversible scarring results in respiratory failure and death.
What causes PF?
Pulmonary fibrosis may result from environmental or occupational exposures such as bacteria, molds, asbestos, silica, and coal dust. It can also be caused by certain medications and radiation treatments. Many medical conditions including systemic lupus erythematosus, sarcoidosis, scleroderma, rheumatoid arthritis, and pneumonia can lead to PF.
So how does genetics play a role?
Approximately 10-15% of individuals with PF have a relative who is also affected by the disease. A number of genes have been associated with pulmonary fibrosis, and a pathogenic alteration within one of these genes can lead to the familial form of PF. Genetic factors have also been shown to play a role in sporadic cases of pulmonary fibrosis. If a specific cause of PF is not identified, the disease is labeled as idiopathic pulmonary fibrosis.
What happened at the PFF Summit?
At the PFF Summit, individuals from 46 states and 12 countries attended sessions on topics ranging from the role of genetics in PF to the critical need for earlier diagnosis of patients with this devastating lung disease. I had the chance to speak with many of the patients, and they all shared a similar experience of having symptoms for many months and even years before they were finally diagnosed with the disease.
Early diagnosis is crucial so that patients have access to medications that have been shown to slow progression in individuals with mild to moderate disease. Accurate diagnosis relies on high resolution CT scans and, in some cases, surgical lung biopsy (SLB); however, the risk of mortality associated with SLB must be weighed carefully. Alternative, less invasive diagnostic procedures are needed so that a SLB may be avoided.
For approximately 20% of patients with PF, genetic testing may aid in the diagnosis and possibly eliminate the need for SLB.
What about treatment?
One of the other topics highlighted at this year’s PFF summit was personalized medicine. There is a growing body of evidence that genetic variants influence the risk of developing PF as well as disease progression and response to therapies. In future clinical trials of treatments for PF, it will be essential to account for genetic variation in order to determine the relationship between genotype and therapeutic response. This will be crucial in improving and personalizing treatments for pulmonary fibrosis.
Should I have genetic testing for PF?
I attended the PFF summit in order to inform and educate clinicians and patients about genetic tests related to lung disorders. GGC’s Comprehensive Pulmonary Panel tests for variants within 93 genes associated with inherited lung diseases. A subset of these genes are linked to pulmonary fibrosis. As new genes are identified as being associated with pulmonary fibrosis, they will be added to the panel so that patients will have access to comprehensive genetic testing. As with any genetic testing, it is important to discuss the potential risks and benefits of having this panel run with a qualified genetic counselor and your clinician.
Answers to Six Important Questions about Genetic Counseling
The Greenwood Genetic Center is home to 14 genetic counselors based across South Carolina to providing services for patients and families for a variety of reasons. But what exactly do they do and how can they be helpful to you? On this first annual Genetic Counselor Awareness Day, read the post below from the National Society of Genetic Counselors for answers to those and other questions about these healthcare providers…
Social and regular media are filled with information about all the genetic tests available and the latest genes discovered by researchers. You can’t help but wonder whether you should be tested and what the results might mean. So where do you turn? Genetic counselors are the professionals who can help guide you.
Wait, genetic what?
“Many people are confused about what a genetic counselor does, and many who might benefit from seeing a genetic counselor may not know we exist,” said Mary Freivogel, president of the National Society of Genetic Counselors (NSGC). “Simply put, genetic counselors have advanced training in medical genetics and counseling and can be a vital part of your healthcare team by helping you understand how inherited diseases and conditions might affect you or your family. We can provide guidance on whether genetic tests may or may not be right for you and help you make informed choices about your healthcare.”
Genetic counselors work in many areas of medicine, including cancer, prenatal, cardiology, neurology, infertility, pediatric and adult. Many work directly with patients in various healthcare settings, while others do research or work in education, public health or in industry settings.
Nov. 9 is Genetic Counselor Awareness Day, the perfect time to answer some questions about this growing and important profession.
Q: My doctor knows my family history. Can’t he or she provide the same kind of guidance I would get from a genetic counselor?
A: Genetic counselors are a part of the healthcare team and work collaboratively with you AND your doctor. Depending on the specialty and training of your doctor, he or she may not have the time and expertise to help you fully understand how genetic diseases and conditions might affect you or your family. Genetic counselors are experts at interpreting and explaining complex genetic information to both you and your doctor while also providing emotional support when necessary. If your genetic counselor and doctor are not in direct contact, be sure to provide any information you learn from a genetic counselor to your doctor so it can be included in your personalized medical management plan.
Q: Can a genetic counselor tell me whether I’ll get a certain disease?
A: Nobody can you tell you if you are going to get a disease or guarantee that you will not get it. Many things can influence your risk for a disease, and your genes are only one of them. A genetic counselor can help you understand your chances of developing a disease or condition. Regardless of your risk level, a genetic counselor can work with you and your doctor to develop a plan, including screening and prevention options.
Q: Is the right time to meet with a genetic counselor after I’ve had my genetic tests?
A: Many people benefit from meeting with a genetic counselor before undergoing a genetic test. A genetic counselor can help you explore whether getting tested is right for you and if so, which test is appropriate and what laboratory should do the test. A genetic counselor can explain what the test can and cannot tell you and can prepare you for the results, which may impact not only you, but members of your family. In some cases, patients choose to decline genetic testing after meeting with a genetic counselor, but still benefit from receiving personalized information about their level of risk, based on their family history and other factors.
Q: Will a genetic counselor tell me what to do based on my test results?
A: A genetic counselor can provide personalized information, guidance and emotional support through the decision-making process but will not tell you what decision to make. Rather, a genetic counselor will help you understand complex genetic information and provide useful insight and perspectives and support you as you make an informed decision about what makes sense for you and your family.
Q: If I need counseling, shouldn’t I see a psychologist or psychotherapist?
A: Genetic counselors counsel, educate and guide patients about their personalized risk for disease, their options for genetic testing and their thoughts and feelings about what they want to know. Genetic information not only affects the individual, but also family members. Some patients can benefit from a genetic counselor’s guidance on how to navigate complex family dynamics when communicating information to relatives. Genetic counselors are not licensed therapists or psychologists but can certainly refer patients for this type of support when necessary.
Q: I think I might benefit from working with a genetic counselor, but what if I can’t afford it?
A: Health insurance often pays for genetic counseling. In many cases, insurance also will pay for a genetic test if it is recommended by a genetic counselor or a doctor. However, you should check with your insurance company to find out if it will pay for the specific test you are considering. A genetic counselor can guide you on how to do this. Your insurance plan may cover certain tests, but not others. An advantage to having genetic counseling is that after you receive the information and insight, you may decide you don’t want or need a genetic test, which can save you money.
Genetic counselors are healthcare providers with unique, specialized skills and knowledge. In the world of genetics, where things are constantly changing and evolving, genetic counselors will guide and support you as you seek more information about how inherited diseases might affect you and your family. To find a genetic counselor near you, visit findageneticcounselor.com.
Want to learn more about what a genetic counselor does? This video from NSGC is a great place to start!
Rett Syndrome Awareness Month officially ends today, but we encourage everyone to continue to learn more about this genetic disorder and support this amazing community which includes families such as the Gunns and the Croissants . We continue our research and clinical care and are excited to also share information regarding a new book on the subject.
Dr. Walter Kaufmann , Director of the Center for Translational Research and Ravenel Boykin Curry Chair in Genetic Therapeutics at the Greenwood Genetic Center, has edited a book on Rett syndrome. The book, Rett Syndrome, is part of the Clinics in Developmental Medicine Series from MacKeith press.
This book is aimed at clinicians and researchers as an overview of the clinical and genetic features of Rett syndrome as well as current status of therapies. Dr. Kaufmann discusses the book below.
When your child with disabilities becomes an adult with disabilities
Our daughter, Kelsey Croissant is 25 years old. Like many women her age, she loves country star Luke Bryan. And like many women her age, she’s not into her parents’ favorite music (which happens to be classic rock). She enjoys traveling to bluegrass festivals, visiting family, swimming, taking long walks in the park, and touring art museums.
But unlike many women her age, Kelsey isn’t celebrating earning her degree, getting settled into her first job, or navigating the dating world. Kelsey is nonverbal. She is unable to walk. She has seizures. She has lost all purposeful hand movements and requires constant care.
Kelsey has Rett Syndrome.
What is Rett syndrome?
Rett syndrome affects approximately 1/10,000 females. Girls with Rett syndrome experience normal development until 6-18 months followed by a period of developmental regression. The features of Rett syndrome include intellectual disability, seizures, absent or reduced speech, and stereotypical hand movements, as well as breathing and digestive issues.
We first suspected something when Kelsey was about a year old. She was not crawling well and had not begun to pull to stand on her own. But she did have a 20 word vocabulary and was self-feeding.
At 14 months old, we saw a developmental physical therapist who said that cognitively and socially she would be fine, but she had low muscle tone. We began physical therapy three times a week. That was difficult for a young couple living far away from family, but, as parents you do what is necessary, and we made it happen.
As Kelsey’s challenges became more worrisome we embarked on a diagnostic journey, bouncing from neurologist to neurologist until finally around age 2, we received the diagnosis of Rett syndrome. Shortly afterward, her developmental regression began. Our baby girl was losing all purposeful hand movements and the few words that had made us beam with pride at one year were gone.
Kelsey’s diagnosis has plunged us into a world we never knew existed. Living with Rett syndrome is a roller coaster –there are ups and downs. As a family we have really learned to appreciate the blessings of each day. We are grateful for the support of the experts at UAB and GGC. That’s where we can ask all of our “crazy” questions that you feel like no one else can possible understand! And Kelsey is doing her part to advance research by participating in the Rett Syndrome Natural History Study.
Where do we turn now?
We can’t say that these past 25 years have been easy. But we remember that our girl is Kelsey first and foremost, and we do not define her based on her diagnosis. She has her own personality and likes and dislikes. We never limit her due to her disability. She has been water skiing, flying in a two seater airplane, bowling, boating, and fishing.
But now, as a young adult, Kelsey has aged out of many of the programs that have supported her. There are a great deal of resources for families with children with special needs, but once they reach adulthood, the challenges are different and the opportunities for inclusion are much more limited.
That’s why we have become actively involved with a grassroots movement in Columbia to develop a mixed-use community for adults with disabilities to live independently, but with support. We are early in the planning process and welcome the involvement of anyone with an interest and a heart for ensuring a future for Kelsey and all men and women with disabilities.
October is Rett Syndrome Awareness Month. To learn more about Rett syndrome, visit www.rettsyndrome.org.
One of the joys of parenthood is hearing your child say these words and phrases for the first time. Toddlers and teenagers alike are notorious for having their own opinions and preferences. Being able to share these thoughts and control some parts of their world is an important step in child development.
But what do parents do when their child isn’t able to talk?When sign language isn’t an option?
Rett syndrome, and other similar neurodevelopmental disorders, robs individuals of the ability to communicate. When verbal communication is no longer an option, families develop incredible means to communicate. Spend time with a family of a girl with Rett syndrome, and you will witness the incredible bond between parent and child. Parents can tell you which look means “I’m hungry,” which sigh says “I’m bored,” which laugh says “This is so much fun,” and which glance is a request for a favorite movie. The love and trust that a child feels for a parent or sibling shines through without speaking. Excitement over a new toy or skill is palpable. Just as parents of infants can interpret a cry, parents of older nonverbal children learn what different sounds and expressions mean. As one mom shared, “The instinct just grows.”
Devices have been developed to improve communication for those who are nonverbal.
Called augmentative communication devices, these can be as simple as a cards with the words “yes” and “no” to as complex as a computer that can track eye movements. These options have obviously been a positive step forward. Amazingly, some parents and families have developed their systems that can be quite complex and attempt to give their family member the ability to communicate more complex ideas. As wonderful as these systems and devices can be, there are parents who say that their daughters connect with them better than devices. Additionally, communication on the go is faster and easier without carrying around pictures or computers.
As incredible as this unspoken communication may be, parents of children with Rett syndrome continue to fight for their daughters. Augmentative communication devices, medication to ease seizures and breathing irregularities, speech therapy, and, most importantly, a CURE. These families continue to fight. Fight for the awareness that being nonverbal doesn’t mean that you can’t understand what is being said to or around you. Fight for their daughter’s right to advance in school and prove her ability to learn.
October is Rett syndrome Awareness Month.
Previous social media campaigns have been built around #notspeaking and #LOUD to highlight the difficulties of those who are nonverbal. Advocates for Rett syndrome continue to use their voices for those who can’t. Maybe you can too. And we can all work together for the day that a girl with Rett syndrome can say “I love you” out loud. You can learn more by visiting www.rettsyndrome.org.
“There are some people who could hear you speak a thousand words and still not understand you. And there are others who will understand without you even speaking a word.”—Yasmin Mogahed
Thanks to Gov. Henry McMaster, SC is officially joining with the Rett syndrome community in honoring those families who face these challenges every month of the year. Join with us in supporting families like the Gunns, whose story is below. Learn a little about Rett syndrome and be a part of advancing research toward a cure!
Makayla was diagnosed with Rett Syndrome in April of 2015 at the age of two.
At about 18 months, we noticed she had started some repetitive hand motions, and her pediatrician was a little concerned that she did not have many words. She had learned some sign language, and was saying ‘mama’ and ‘dada’, but that was it. Then she suddenly stopped all of that. At her 2 year old check-up, the pediatrician referred us to BabyNet, SC’s early intervention program. Our BabyNet caseworker recommended that she be evaluated by the Greenwood Genetic Center.
We met with Dr. Mike Lyons at GGC’s North Charleston office. He evaluated Makayla and suggested some genetic testing. A few weeks later, he broke the difficult news of Makalya’s diagnosis in a most gracious way. He also immediately recommended we meet with Dr. Steve Skinner in the Greenwood office, who is an expert in Rett syndrome. Though we were overwhelmed at all we needed to know, Dr. Skinner, Fran Annese, and the whole staff were wonderful at that first meeting, giving us all the time we needed to ask questions. Their compassion for families like ours really showed through that day and continues to this day. They have remained accessible and informative, staying up to date on any changes or developments related to Rett syndrome and sharing those as appropriate. They have been so encouraging for our family as we navigate through what, for us, are uncharted and scary waters. We have also enrolled in the Rett Syndrome Natural History Study through GGC.
But, Rett Syndrome does not define Makayla.
Despite her diagnosis of Rett syndrome, Makayla is a happy little girl. We are blessed that she can do the things she can do! She can still walk, unlike so many girls with Rett syndrome, but she also skips and runs in short distances when she is excited. She loves being outside, and her favorite thing to do is play in water, at the pool, the beach, and even in the bathtub. Close behind that is riding her rocking horse, which she would stay on for hours if we let her.
She also loves to watch sports, particularly basketball and football. With four older brothers, she has had many opportunities to watch games! And, she loves to dance, especially to Michael Jackson and Johnny Cash!
Makayla’s diagnosis has been an incredible challenge for our family, but learning about and dealing with Makayla’s condition has done a couple of amazing things. First, it has drawn us closer together as a family. Second, it has brought out a love in each of us that we just did not know was there. I do not think there is any sweeter sound than when Makayla gets tickled and laughs and laughs. Our boys at times even vie for a turn at holding her, and often we have to kick them out of her room at bedtime! She has and continues to bless our family in so many ways.
Many healthcare providers still refer to newborn screening as “the PKU test”, since PKU (phenylketonuria) was the first and only condition screened for beginning in 1965. Thanks to the development of the blood spot card in 1963 by Dr. Robert Guthrie , all babies have a few drops of blood taken from their heel shortly after birth. We started out by looking for only PKU, and in the past 50 years, countless individuals with PKU have been identified and started on treatment – treatment that has prevented intellectual disability, seizures, and growth problems, and that’s amazing!
But newborn screening didn’t stop there!
Today’s test is so much more thanks to a combination of new technologies and new treatments. Technology has rapidly advanced in the 50-plus years of the newborn screening era, allowing us to detect many more disorders. A lot gets done with those few drops of blood – metabolic testing, hemoglobin testing, and more. Testing for some of the newest additions to the newborn screen, lysosomal storage disorders, only requires a tiny fraction of the blood collected from each baby, but requires new, high-tech instruments in the laboratory. Newborn screening now goes even beyond the blood test with non-invasive equipment used to check hearing and pulse oxygen (to identify heart disease).
Thankfully, along with advances in diagnosing these conditions, progress is also being made in the development of effective treatments.
The original treatment for PKU was (and still is) dietary management. With the right advice from geneticists and metabolic dietitians and a lot of careful attention to food intake from the family, the adverse effects of PKU can be avoided. This is not extraordinarily high-tech, but is very effective .
Many other conditions detected by newborn screening can be managed with diet and supplements or with a single medication (like thyroid hormone replacement for patients with congenital hypothyroidism). Patients with hearing loss identified at birth may benefit from the early use of hearing aids or cochlear implants, leading to not only better hearing, but also improved development and speech. Congenital heart defects that may have gone undetected for months, or even years, can often be surgically corrected right away. Other disorders, like cystic fibrosis and sickle cell disease don’t have a single treatment yet, but do have improved outcomes with early detection and comprehensive medical care.
For some of the most recent additions to our newborn screening panel, patients are unable to make a needed enzyme, so novel treatments like enzyme replacement therapy (replacing the missing enzyme with a medication) or bone marrow transplant (introducing healthy cells that can make the missing enzyme) are improving symptoms and quality of life. Advancing technology has made these medications and procedures available and they can be life-saving for patients with these rare diseases.
So, how did we get to the 50+ conditions that South Carolina currently screens?
Each state determines which conditions are on their newborn screen, but all states now try to follow the national Recommended Uniform Screening Panel (RUSP) of 34 core conditions and 26 secondary conditions. Anyone can nominate a condition for the RUSP, and often this is a combination of parents/advocates and researchers. Conditions are added to the RUSP after a committee reviews the scientific knowledge about the condition and the screening test. The reviewers are looking for an overall benefit of screening and whether it can be practically implemented, including things like:
The condition is a serious health issue
Enough is known about the rare disorder to be certain about the diagnosis
An effective treatment exists
Screening can provide quick results
States can provide the screening with reasonable expenses
Most or all babies with the condition will be detected, without too many false-positive results
Not all conditions will be approved, but as we continue to better understand how these conditions can be diagnosed and treated, the list is sure to keep growing. For example, Pompe disease was initially declined because of a few pieces of lacking evidence, but about 5 years later it was added to the RUSP. Soon newborns in South Carolina will be screened for this condition and given the chance to receive early treatment with a synthetic enzyme that will improve survival and quality of life.
Where are we going from here?
As new testing methodologies and treatment options become available, more and more conditions will be recommended and approved for newborn screening. It is truly an exciting time to be in genetics, as we are in the midst of amazing research and discoveries that are not only treating patients after symptoms develop, but with early detection, can prevent children and their families from the devastating effects of many of these conditions.
Dr. Guthrie likely couldn’t dream of the number of lives his innovation would save! The ‘PKU test’ has come a long way, and we are excited to see how families will continue to benefit as progress continues.
That is the approximate number of babies born each year with a condition detectable by newborn screening in the US. This means that thousands of newborns are identified and able to receive treatment preventing permanent health and developmental damage. In some cases, these treatments save the baby’s life before they ever even have a symptom. I don’t know about you, but I think that’s pretty impressive.
While many new parents may be aware that their baby gets a little heel stick before they are sent home from the hospital, most probably do not realize the full extent of what goes on behind the scenes once that dried blood spot card is collected and what it could mean for their baby’s health. Given that it is probably one of the most successful public health initiatives of all time screening millions of babies over the last 54 years of its existence, newborn screening tends to fly under the radar as an unsung hero in healthcare.
September is Newborn Screening Awareness month!
So we want to take this opportunity to share some facts about newborn screening, acknowledge the teams of healthcare providers and laboratories that make these programs possible, and let some of the amazing parents we work with at the Greenwood Genetic Center share their story with you. Read on below for more info and stay tuned for the rest of the month for more posts!
Let’s start with some basic facts.
What is newborn screening? How is it done? And, what conditions are included?
Each baby born in the US is required by law to have newborn screening. For most babies, this means they get a heel stick after the first 24 hours of life before they are sent home from the hospital. Several drops of blood are collected on a filter paper card and then sent to a state lab for testing. In addition to the blood test, newborn screening also includes a hearing screen in all states and pulse oximetry (to screen for heart defects) in some states. Each state in the US runs its own newborn screening program, so the number of conditions included and the process for the screening varies from state to state. The Recommended Uniform Screening Panel, or “RUSP”, is a list of 34 core conditions recommended on a national level to provide some guidance and consistency among the individual state programs. Most states screen for at least these 34 core conditions, but some states elect to screen for more and may include closer to 60 conditions.
How do you decide which conditions to test?
In order for a condition to make it on the list for newborn screening, it has to meet some criteria first. These include:
A “good” screening test for that condition exists. “Good” means that the test is sensitive and specific enough to pick up all babies with the disorder without too many false positives. It must also fit somewhat within the current structure and methods of newborn screening and be cost effective since millions of babies will be screened every year.
An effective treatment is available for the condition.
There is evidence to support the benefit of screening babies at birth before any symptoms may be present. This means that by identifying these babies right after birth and starting treatment early, future health complications or cognitive impairment can be lessened or prevented altogether before any symptoms are even present. Without newborn screening, these babies wouldn’t be diagnosed until much later when symptoms develop and by then, irreversible damage will have already occurred.
So, how does GGC figure into all of this?
In South Carolina, the Greenwood Genetic Center (GGC) has a long standing relationship with the Department of Health and Environmental Control’s (DHEC’s) SC Newborn Screening Program. The Center follows-up on screening results that are abnormal for one of the inherited metabolic or genetic conditions included on the panel. This is where the GGC’s Clinical Metabolic Team comes in. The team includes metabolic geneticists, a genetic counselor, dietitians, a psychologist, and clinic coordinators. Initially, they consult with the pediatricians and recommend any additional testing. Once the diagnosis is confirmed, the metabolic team will follow that child on a regular basis. They educate the family about the diagnosis and counsel them on the recurrence risk. They initiate and manage a treatment plan as well as help the family navigate other medical and developmental needs related to their diagnosis.
The GGC Diagnostic Laboratory performs much of the follow-up testing for these abnormal screens as well as the tests used to monitor the effectiveness of the treatment or diet. The tests that are done as part of the NBS follow-up process have some of the fastest turnaround times of any of our tests in the lab. Getting an answer fast is critical for these babies so treatment can begin as soon as possible. This experience and expertise has allowed the GGC Diagnostic Lab to expand outside of South Carolina. The lab now also works with a few other states in providing follow-up testing for some of the lysosomal storage disorders recently added to the NBS programs in other states and hopes to continue to grow these services.
We are proud of our metabolic clinical team and the diagnostic lab contributions to newborn screening in South Carolina and look forward to sharing more with you throughout the month!
Families are never fully prepared to learn that their beloved baby has a birth defect, but one SC mom is working to make their road a little less rocky by sharing her own story and advocating for the littlest patients.
Stephen and Jenna Brown of Hanahan, SC were eagerly anticipating the birth of their first child, Harper. They found out she was a girl at a 15 week ultrasound and had seen her beautiful face at a keepsake 17 week scan. Feeling excited and confident, Jenna went alone to her doctor’s office for her routine 18 week ultrasound. Though Stephen offered to come, Jenna had resisted, wanting him to go to work and have more time off when the baby arrived.
“When the doctor came in, the ultrasound tech reached out and took my hand. That was my first sinking moment of despair,” shared Jenna.
There was a cyst at the bottom of Harper’s spine, possibly spina bifida.
‘My daughter will never walk,’ was her first thought. As she waited in the office holding her daughter’s ultrasound picture and crying, Jenna texted her husband. Later that day they were worked in at the Medical University of SC (MUSC).
Spina bifida was confirmed.
The Browns elected to pursue in-utero surgery which could provide Harper with the best hope for a positive outcome. After an amniocentesis and two long weeks of waiting, they drove to Philadelphia where the highly-specialized surgery is performed, ready to put their life on hold for baby Harper. Jenna endured 12 hours of testing only to learn that she was not a candidate for the procedure.
“We left Philadelphia devastated,” she said. “They reevaluated us at 25 weeks, but we still were not eligible for the surgery.”
At that point, the Browns met with Dr. Ramin Eskandari, a pediatric neurosurgeon at MUSC, to discuss Harper’s surgery after delivery. “He was the first one who gave us hope,” said Jenna. “This was not the worst-case scenario we had read about on the internet, maybe her lesion was even covered!” When spina bifida lesions are covered they are protected from the damaging effects of the amniotic fluid.
The Browns followed up at MUSC every two weeks until Harper was delivered on June 17, 2015, with family in the waiting room wearing their ‘Hope for Harper’ t-shirts.
After delivery, Harper was whisked away for an evaluation, and Stephen went with her. “He came back to my room with tears flowing, but couldn’t get the words out.”
My heart sank again, but he said ‘No, it’s good – it’s covered.’
The next day Harper had her closure surgery. She went home on June 24th, her original due date.
Jane Dean of GGC’s SC Birth Defects Prevention Program met the family when Harper was about a month old. “I immediately fell in love with this strong, amazing family.” Dean provided counseling and information and enrolled the family into GGC’s folic acid study.
“I was taking folic acid during my pregnancy,” shared Jenna, “so I wanted to help understand what other factors may be involved – why it didn’t work for Harper.”
Since Harper’s birth, Jenna has left her teaching career to become a full-time mom. Harper is thriving. She is walking and running thanks to successful surgeries and ongoing physical and occupational therapy. Now, Jenna and Harper spend their days volunteering with MUSC’s Children’s Hospital, hosting events, advocating for patients, and attending appointments with families who are facing the same challenges they have endured – providing hope.
Jenna also recently joined Dean at a bridal show in Charleston to help promote the importance of folic acid before and during pregnancy.
“Your story could be different, your journey could be different than what you planned,” said Jenna. “Ours is, but there is always hope.”
Fragile X syndrome is the most common inherited form of intellectual disability. Approximately 1/4,000 males and 1/8,000 of females are impacted by this disorder which causes distinctive physical characteristics including a triangular-shaped face, large ears, a prominent chin, and broad forehead. Individuals with Fragile X also experience significant developmental delays, varying degrees of intellectual disability and autistic-like behaviors.
The genetic cause for Fragile X syndrome was identified in 1991, during the early years of the Human Genome Project. The Fragile X syndrome gene, FMR1, is located on the X chromosome. Females have two copies of the X chromosome, while males have only one. This is why males are more frequently and severely affected by Fragile X syndrome. When the FMR1 gene is mutated, it is unable to produce a protein that is vital for healthy brain development.
In the 26 years since the genetic cause was found, rapid progress has been made, including understanding of the pathophysiology of the condition, the development of animal models, and the identification of drugs that correct the features of Fragile X in mouse models.
This relatively rapid progress caused great excitement among the Fragile X community, and numerous clinical trials have been implemented in the past decade – nearly all have failed, showing no improvement.
But if we’ve learned so much about Fragile X, why haven’t we made more progress in treating it?
Walter Kaufmann, MD, the senior author of the study, says much of it has to do with how we are measuring the impact of the drugs.
In a review of 22 clinical trials that have been conducted on individuals with Fragile X syndrome, Kaufmann and his coauthors found that the trials failed in part because of the deficiencies of the outcome measures.
Outcome measures are the ways that researchers evaluate whether or not the study drug is having an effect. They can include self-report measures such as behavioral questionnaires, performance-based measures such as IQ tests, or even physiological measures such as biomarkers in the blood that may change with treatment. Outcome measures are compared before, during and after the clinical trial to assess the efficacy or impact of the drug.
“Part of the problem with these trials is that the tools that are being used to measure the drugs’ effectiveness are of limited or moderate quality,” said Kaufmann. “Many of the current outcome measures being used to assess cognitive improvement and behavioral changes in response to the drugs have not been proven to have reliability, validity or sensitivity to treatment.”
“These drugs may have had a benefit to the patient, but if we’re not able to measure that within the context and timeframe of the study, it is considered a failure,” he said. “And without concrete evidence to show efficacy, the trials are halted or never progress to the next level.”
Another shortcoming of the measures is that many are intended for long-term assessment, rather that the relatively short duration of most clinical trials.
If scientists can’t objectively and consistently show that a drug is having a meaningful impact on function and quality of life, the NIH and FDA will not move these trials forward toward an effective treatment, Kaufmann said.
“Measures for Fragile X syndrome were evaluated for this study because of the numerous clinical trials already done for this disorder,” said Kaufmann, “but the same issues exist for other neurodevelopmental disorders, including autism. We must be able to quantitatively demonstrate therapeutic efficacy for these complex disorders. That is the key to success.”
What are we doing about it?
Since joining GGC in 2015, Kaufmann and his team have been committed to advancing clinical trials for neurodevelopmental disorders, including Fragile X syndrome, Rett syndrome, and autism. A key goal of GGC’s Center for Translational Research, which is headed by Kaufmann, has been to develop effective outcome measures for these disorders including scales, questionnaires, and biomarkers.
Dr. Walter Kaufmann is the Ravenel Boykin Curry Chair in Genetic Therapeutics and Director of the Center for Translational Research (CTR) in the Greenwood Genetic Center. Coauthors on this study include researchers from Johns Hopkins University School of Medicine, Rush University, Cincinnati Children’s Hospital, Stanford University, University of California Davis, and Novartis Pharmaceuticals