Genetic screening is vital for early diagnosis and management of genetic diseases. In this episode, dig into how it works, how it can help treatments reach patients sooner, and how it informs traditional treatments like physical therapy.
Genetic screening works to determine which people might have a greater likelihood of developing a specific trait or disease, while genetic testing is concerned with testing an individual for a specific condition.
One method of screening takes the form of a DNA-sized probe to track when its identical sequence is discovered inside the cell. And once that matching code is found and additional tests confirm the match, genetic testing may be conducted, a diagnosis reached, and then treatment prescribed.
There are many different types of screenings, including prenatal genetic screening, which can range from testing amniotic fluid, drawing blood from the mother, and even taking a sample of embryonic cells formed by in-vitro fertilization.
Newborn genetic screening has not only increased the potential for revolutionary treatments to be successful, but it has also dramatically improved other forms of care, like physical therapy.
Spinal muscular atrophy, or SMA, is a disease that affects approximately one in 11,000 infants. When SMA is identified early through screening, the role of physical therapy can be radically different than if the infant hadn’t undergone screening or been formally diagnosed with SMA.
In newborns who aren’t screened, or whose condition is not discovered so early, physical therapy plans may be designed to provide their atrophying muscles with physical support.
But when the condition is identified early, physical therapy can do so much more. It changes from care that focuses on making the baby as physically comfortable as possible to one that can potentially help them reach physical milestones.
Newborn genetic screening has dramatically changed the way specific diseases progress by providing personalized treatment. As treatments become more sophisticated and targeted, they can truly transform a child’s life, especially when administered early.
DDx SEASON 4, EPISODE 6
The Importance of Genetic Screening
RAJ: This season of DDx is brought to you by Novartis Gene Therapies.
The following case study has been changed to preserve confidentiality.
KIM: It was the summer of 2021 and a couple in California were about to receive a phone call that would turn their world upside down. Seven days earlier they were in the hospital, where their first child — a little baby boy — was born. It was a successful delivery and the baby looked healthy. A few hours afterwards, a nurse pricked the infant’s heel with a needle to get a few drops of blood for a routine genetic screening.
That genetic screening included 80 conditions,1 including spinal muscular atrophy, or SMA,2 a disease that affects approximately one in 11,000 infants.3
SMA weakens muscles, so much so that breathing and eating can become impossible.4 In most common variations of the disease, babies born with SMA aren’t expected to survive beyond the age of two.4
And on this day in June, the phone rang and the couple heard the voice of their pediatrician, informing them that one of the genetic tests had come back positive.
The family would later learn that their baby had one of the most severe forms of SMA, called SMA type 1.3
This condition used to be a death sentence. But not anymore.3,5
And what happened over the next 19 days would prove it.
RAJ: This is DDx, a podcast from Figure 1 about how doctors think.
I’m Dr. Raj Bhardwaj.
KIM: And I’m Kim Handysides.
RAJ: Today Kim is joining me to talk about the importance of genetic screening when it comes to early diagnosis and the management of diseases.
KIM: We’ll begin by looking at how genetic screening works, the way it allows ground-breaking treatments to reach patients earlier, and how it has informed traditional treatments like physical therapy.
RAJ: The prognosis for some life-threatening diseases has been turned on its head.
KIM: It’s well-known that specific genetic characteristics can be passed down from parent to child.6,7 But understanding the mechanism within DNA that allows a child to inherit, say, blue eyes or curly hair, has been the subject of more recent scientific discovery.7
One of the major advances that aided scientists in their understanding of inherited traits was the Human Genome Project. The mapping of the human genome decoded the body’s DNA and revealed a blueprint8 that, among many things, allowed inherited traits to be understood and tracked across multiple generations.9
Aided by the Human Genome Project, geneticists continued the laborious work of matching traits to chromosomes. Over time they were able to discover which genes caused major genetic illnesses, including cystic fibrosis, sickle-cell anemia, and Huntington’s disease.10
These are all monogenic conditions, which means they’re caused by variation in a single gene.7,9 And if you happen to have that variation, the chances of you developing the disease are very high.11 Other conditions are caused by variations across multiple genes, which makes the work of identifying them much more challenging.9 In fact, scientists are still working to understand the complex relationship between genes and the development of specific diseases.12
And even after scientists have matched a genetic sequence to a disease, there are more hurdles to overcome. Before disease management can begin, a tool must be designed to detect the variant genes.13
And that tool is genetic screening.
Genetic screening works to determine which people might have a greater likelihood of developing a specific trait or disease, while genetic testing is concerned with testing an individual for a specific condition.14
One method of genetic screening takes the form of a DNA-sized probe to track when its identical sequence is discovered inside the cell.15 And once that matching code is found and additional tests confirm the match, genetic testing may be conducted, a diagnosis reached, and then treatment prescribed.
There are many different types of genetic screening, including prenatal genetic screening, which can range from testing amniotic fluid, drawing blood from the mother, and even taking a sample of embryonic cells formed by in-vitro fertilization.16
A typical newborn genetic screening looks for a number of conditions, including sickle cell disease, cystic fibrosis, and severe combined immunodeficiencies.17,18
In the case of our newborn with SMA — like all those with SMA — he was missing a gene that makes the proteins that allow motor neurons to work.19
In 1995, scientists discovered which precise gene was missing from those with SMA, which later led to a handful of remarkable innovations surrounding treatment.20
One of which introduces copies of the missing gene into a person’s cells, and causes the body to start producing the protein that allows motor neurons and muscles to function.21
When it comes to genetic disorders, diagnosing and treating a disease quickly is paramount.22
For example, when a baby is born with SMA type 1, half of their motor neurons have already been lost to the disease.23
If too many motor neurons are damaged, treatment is less effective,24 and the chances they’ll ever learn to sit up, let alone walk or run, are extremely small. Life expectancy for infants with SMA type 1 is about two years.5
But if a baby is treated early, the results can be transformative.24 After treatment, babies with even the most severe form of the disease may reach significant physical developmental milestones, including sitting and walking.5,19
Our newborn with SMA type 1 was one of them.
Thanks to genetic screening, he was able to start treatment at 19 days old, which gave his body the ability to start producing the necessary proteins to make his motor neurons function properly.5,21
His parents were awestruck.
His muscles grew and developed. At 5 months old, he didn’t show any outward symptoms of this once-fatal disease.
KIM: Newborn genetic screening has not only increased the potential for revolutionary treatments to be successful, but it has also dramatically improved other forms of care, like physical therapy.
Let’s go back to our infant with SMA.
And let’s start talking about this case as a hypothetical.
Because genetic screening identified our infant as having SMA when he was just a week old — and he started receiving treatment less than two weeks later — the role of physical therapy can be radically different than if the infant hadn’t undergone screening or been formally diagnosed with SMA.26
In newborns who aren’t screened, or whose condition is not discovered so early, physical therapy plans may be designed to provide their atrophying muscles with physical support.19,26
For example, an infant with SMA type 1 would generally require physical therapy several times a week, coupled with specialized physical supports and equipment. This kind of physical therapy can help the baby use what mobility they have to best engage with their family and environment.3,26
But when genetic screening identifies a specific neuromuscular condition like SMA early, physical therapy can do so much more. It changes from care that focuses on making the baby as physically comfortable as possible to one that can potentially help them reach physical milestones.26
Newborn genetic screening has dramatically changed the way specific diseases progress by providing personalized treatment. As treatments become more sophisticated and targeted, they can truly transform a child’s life, especially when administered early.5,27
RAJ: Special thanks to Dr. Emily Grant and Tina Duong, a clinical researcher in neurology and physical therapist at Stanford University School of Medicine, for sharing their expertise in the research of this episode.
This is DDx, a podcast by Figure 1.
Figure 1 is an app that lets doctors share clinical images and knowledge about difficult to diagnose cases.
I’m Dr. Raj Bhardwaj, co-host and story editor of DDx. You can follow me on Twitter at Raj BhardwajMD.
Head over to “figure one dot com slash ddx”, where you can find full show notes, photos and speaker bios.
This episode was brought to you by Novartis Gene Therapies.
For more education on gene therapy, visit gene therapy network dot com.
Thanks for listening.
- Newborn Screening Program. California Department of Public Health. Accessed October 14, 2021. https://www.cdph.ca.gov/Programs/CFH/DGDS/Pages/nbs/default.aspx
- Recommended Uniform Screening Panel (RUSP) Core Conditions. California Department of Public Health. Accessed October 14, 2021. https://www.cdph.ca.gov/Programs/CFH/DGDS/CDPH%20Document%20Library/NBS%20Documents/FINAL_CoreDisordersScreenedCA2020October.pdf
- Mercuri E, Finkel RS, Muntoni F, et al. Diagnosis and management of spinal muscular atrophy: Part 1: Recommendations for diagnosis, rehabilitation, orthopedic and nutritional care. Neuromuscul Disord. 2018;28(2):103-115.
- Spinal Muscular Atrophy 1: Symptoms. NIH. Genetic and Rare Disease Information. Updated August 2019. Accessed October 14, 2021. https://rarediseases.info.nih.gov/diseases/7883/spinal-muscular-atrophy-1
- New Gene Therapy Poised to Transform Care for Spinal Muscular Atrophy. University of Rochester Medical Center. Published June 2019. Accessed October 16, 2021. https://www.urmc.rochester.edu/news/story/new-gene-therapy-poised-to-transform-care-for-spinal-muscular-atrophy
- What is a gene variant and how do variants occur? MedlinePlus. Accessed October 17, 2021. https://medlineplus.gov/genetics/understanding/mutationsanddisorders/genemutation/
- Graves J, Shine J. The Human Genome Project—discovering the human blueprint. Australian Academy of Science. Accessed October 17, 2021. https://www.science.org.au/curious/people-medicine/human-genome-project
- The Human Genome Project. National Human Genome Research Institute. Accessed October 16, 2021. https://www.genome.gov/human-genome-project
- Genetic Disorder. National Human Genome Research Institute. Accessed October 19, 2021. https://www.genome.gov/For-Patients-and-Families/Genetic-Disorders
- Collins FS, McKusick VA, Jegalian, K. Implications of the Genome Project for Medical Science. National Human Genome Research Institute. Accessed October 19, 2021. https://www.genome.gov/25019925/online-education-kit-implications-of-the-genome-project-for-medical-science
- Hernandez LM, Blazer DG, Institute of Medicine (US) Committee on Assessing Interactions Among Social, Behavioral, and Genetic Factors in Health, eds. Genes, Behavior, and the Social Environment: Moving Beyond the Nature/Nurture Debate. Washington (DC): National Academies Press (US); 2006.
- Craig J. Complex Diseases: Research and Applications. Nature Education. 2008;1(1)184.
- Collins FS, Fink L. The Human Genome Project. Alcohol Health Res World. 1995;19(3):190-195.
- Genetic Screening. National Human Genome Research Institute. Accessed October 20, 2021. https://www.genome.gov/genetics-glossary/Genetic-Screening
- Probe. National Human Genome Research Institute. Accessed October 17, 2021. https://www.genome.gov/genetics-glossary/Probe
- Genetic testing: Muscular Dystrophy. NHS. Accessed October 16, 2021. https://www.nhs.uk/conditions/muscular-dystrophy/genetic-tests/
- Diseases Screened. Newborn Screening Ontario. Accessed October 20, 2021. https://www.newbornscreening.on.ca/en/about-screening/diseases-screened
- Recommended Uniform Screening Panel. Health Resources and Services Administration. Accessed November 16, 2021. https://www.hrsa.gov/advisory-committees/heritable-disorders/rusp/index.html
- Spinal Muscular Atrophy Fact Sheet. National Institute of Neurological Disorders and Stroke. Accessed October 19, 2021. https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Spinal-Muscular-Atrophy-Fact-Sheet
- The Discovery of SMA. CureSMA. Published March 2018. Accessed October 17, 2021. https://www.curesma.org/the-discovery-of-sma/
- Gene Therapy for Spinal Muscular Atrophy (SMA). Children’s Hospital of Philadelphia. Accessed October 19, 2021. https://www.chop.edu/treatments/gene-therapy-spinal-muscular-atrophy-sma
- What is Newborn Screening? CureSMA. October 19, 2021. https://www.curesma.org/newborn-screening-for-sma/
- Emmady PD, Bodle J. Werdnig Hoffmann Disease. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2021.
- Glascock J, Sampson J, Haidet-Phillips A, et al. Treatment Algorithm for Infants Diagnosed with Spinal Muscular Atrophy through Newborn Screening. J Neuromuscul Dis. 2018;5(2):145-158.
- ‘Like Looking at a Miracle’: Baby Blossoms Thanks to Gene Therapy. Seattle Children’s Hospital. Published May 31, 2019. Accessed October 15, 2021. https://pulse.seattlechildrens.org/like-looking-at-a-miracle-baby-blossoms-thanks-to-gene-therapy/
- Physical Therapy Guide to Spinal Muscular Atrophy. Choose PT. Accessed October 20, 2021. https://www.choosept.com/guide/physical-therapy-guide-spinal-muscular-atrophy
- Newborn Screening for Neuromuscular Diseases. Muscular Dystrophy Association. Accessed October 15, 2021. https://mda.donordrive.com/index.cfm?fuseaction=donate.event&eventID=824