Spinal muscular atrophy (SMA) is a severe, neuromuscular disease that over time leads to the inability to walk, eat, or breathe. SMA is the leading genetic cause of infant death. The condition is inherited in an autosomal recessive manner, meaning those with the disease inherited two dysfunctional copies of the gene, one from each parent. Since carriers of the condition do not show symptoms, many individuals do not know they are carriers until they have a child with the disorder. While carrier screening for SMA began in the late 1990’s and is now widely available via most academic and commercial genetic testing laboratories, access to this testing is still somewhat limited, especially prior to getting pregnant. Knowing one’s carrier status before conceiving a pregnancy allows a couple to consider all of their reproductive options, including preimplantation genetic testing (PGT). PGT can help prevent carrier couples from having a child with SMA.
The importance of preconception carrier screening is reflected in many of the stories told by the families of those with SMA. Some parents are passionate about improving access to carrier screening because of their own experience. Kathleen’s parents were healthy, well-educated individuals just starting their professional careers when they tried to get pregnant. After a few months of trying without success and a miscarriage, they were referred to a specialist as a precaution. They had no significant personal or family medical history, and no findings on physical exam that would be of concern. At that visit, they were offered cystic fibrosis (CF) carrier screening, the only genetic carrier screening recommended by the American College of Obstetrics and Gynecology (ACOG) for individuals of their ethnicity at the time.1 No other testing was recommended. CF testing came back negative and they continued trying to conceive naturally.
The couple ultimately conceived just a few months later without the need for assisted reproductive technology. Some unrelated issues during the last weeks of the pregnancy resulted in an early induction, but their daughter, Kathleeen, was delivered without incident. Despite a brief NICU stay, she seemed to be doing well. That changed drastically over the course of the next five weeks.
Kathleen’s mother has a background in medicine and suspected that her daughter had low muscle tone. At a week six appointment, the evaluation of an astute pediatrician led to an immediate referral to a neurologist who, following genetic testing, confirmed a diagnosis of SMA type 1. This news was devastating. Like many parents who receive this diagnosis, Kathleen’s parents had never heard of SMA. Their frantic research added to their devastation as they realized the magnitude of their daughter’s illness. They evaluated all of their options, speaking with specialists and families across the country, and ultimately decided it was most important to keep Kathleen comfortable. “We didn’t care an ounce about extending the quantity of her life. We wanted to focus on the quality of her life.” They elected hospice and palliative care and spent every moment possible with their beloved daughter. Kathleen passed away peacefully in her mother’s arms on her 9 month birthday.
Oliver was born in August of 2008. His parents went through eleven years of infertility before ultimately conceiving Oliver via the assistance of medication and timed intercourse. During their fertility evaluation they, too, underwent carrier screening for cystic fibrosis according to the guidelines of the time. Their results were negative. Oliver was diagnosed with SMA at three months of age. He died just two days shy of his first birthday. His parents spent that year celebrating all of his firsts. “We made a point of celebrating what we could celebrate,” his mother says. “We got one of everything with him…except a birthday.”
Kathleen’s parents have gone on to have two more biological children and an adopted son. With both of their pregnancies, they elected to have an early diagnostic test for SMA, called chorionic villus sampling (CVS). Both times, testing indicated that the baby was unaffected. Had the results been positive, the couple indicated that they would have terminated. While they were aware of the availability of PGT for SMA, they did not want to go through IVF at the time. “We certainly would have done it,” they said, especially if they had had to terminate a pregnancy. “We would rather say goodbye early than have another child have to face all of the challenges of SMA.”
Oliver’s parents did opt for IVF with PGT for their second pregnancy, undergoing the procedure just months after Oliver’s death. His mother was advanced maternal age, and given how long it had taken to get pregnant with him, the couple was concerned they might be running out of time. From 17 harvested eggs, the couple ended up with just two embryos that did not have SMA, both of which were transferred and both of which implanted. Twins! Oliver’s brother and sister decided to make an early entrance though, born at just 25 weeks. Their first year was equally as challenging, with major medical complications keeping Oliver’s brother in the NICU for over 100 days. Their story is a reminder that PGT is not a guarantee of a healthy child, just one free of the genetic disease in question. Despite their early struggles, though, the twins are now thriving. At ten years old, their mother says “looking at them, you would never know.”
Since Kathleen and Oliver were born, ACOG has come out in support of universal screening for SMA. That means offering screening to everyone, regardless of their family history. They also acknowledge the importance of preconception screening, where possible, to give couples the opportunity to consider all options for conceiving a pregnancy. Early screening is also beneficial now that new treatments for SMA have been introduced, as they have been shown to be most effective when administered as early as possible following birth. The increased awareness and affordability of expanded carrier screening has helped address this need, allowing couples to discover their carrier status for SMA and a number of other conditions long before they achieve a pregnancy.
Whether or not to pursue IVF with PGT for SMA is influenced by many factors. Recent research2 done by genetic counselor Mackenzie Blaile suggests that cost is one of the most significant barriers. Oliver’s parents were fortunate to work for a company whose insurance plan covered a large portion of the cost. That is, unfortunately, not the case for many. Even in cases where insurance covers some of the costs, the remaining out of pocket expenses may not be feasible for some families. Reducing the cost of the procedure, advocating for insurance coverage, and helping families find alternate means of funding IVF with PGT is a top priority for those that work in the field.
Another major consideration is the relatively recent release of a treatment for SMA. The FDA approved the first drug to treat SMA in 2016. In initial trials, the drug, called Spinraza, was given to individuals with infantile onset of the disease and demonstrated notable improvement in motor milestones for 40% of children that received the drug. During the same time period, no significant improvements were observed in the control group. Based on that data, the FDA fast tracked approval of the drug. While the availability of treatment offers tremendous hope for families who have a child with SMA, the long term efficacy of the drug and why it may be ineffective for some remains unknown. There is currently one other FDA approved treatment for SMA and six more being investigated in clinical trials.
Ms. Blaile’s research showed that the availability of treatment for SMA has complicated reproductive decision making for families who already have a child with SMA but may be considering growing their family. Some parents are less concerned about having another affected child given the availability of Spinraza and other therapies, particularly if those therapies have been effective for their existing child. Others feel that utilizing technology like PGT to avoid having a child with SMA is unethical or unnecessary now that treatment is available. These feelings may also be reflected in those who are carriers of the condition, even if they have not already had an affected child. Alternately, families in either situation may decide that having a child with SMA still presents significant medical, emotional, and financial challenges and therefore opt for a reproductive option aimed at prevention to grow their family. All of these feelings are valid and deserve to be fully and openly discussed so families can determine the best option for them.
Kathleen and Oliver’s parents share their journey with SMA not because they believe their decisions are right for all families. They share because they firmly believe in options…and education. “Families need comprehensive, unbiased information,” Kathleen’s parents emphasize. Meeting with a genetic counselor can help facilitate this type of open discussion and ensure access to complete, objective information about SMA, carrier screening, treatment options, and reproductive decision-making.
A heartfelt thank you to Kathleen and Oliver and their parents for lending their story to help provide a real-life context for this post. And sincere thanks to genetic counselor, Mackenzie Blaile, whose research about reproductive decision making with SMA families helped inform this piece. For additional information about SMA, please go to www.curesma.org.
Jessica Greenwood is an independent consultant to Sharing Health Genes. As a licensed genetic counselor and digital health consultant, she works with health-related organizations looking to deliver memorable messages of health in the digital space. Mrs. Greenwood started her career in a clinical role, working for eight years as a preconception and prenatal genetic counselor before transitioning to industry. Mrs. Greenwood completed a year-long certificate program in Digital Health Communication at Tufts University that spearheaded her work in digital health. She now consults with health-related organizations, assisting with the creation and execution of a digital strategy including the development of health literate patient-centered educational materials. Mrs. Greenwood earned a Bachelor of Science degree from North Carolina State University with a minor in Genetics and a Master of Science in Genetic Counseling from the University of North Carolina at Greensboro.
- Of note, the American College of Medical Genetics started recommending SMA carrier screening for all couples regardless of ethnicity in 2008.
- Unpublished work. Findings presented at the CureSMA Annual Conference Clinical Care Meeting, June 27th, 2019, Anaheim, CA.