This week, SMA was added to the list of required medical screenings every baby in Texas receives at birth. Without newborn screening, many children escape the diagnosis until after permanent neuromuscular damage has occurred. Early recognition and treatment can mean the difference between a near normal life or suffering many skeletal deformities and being unable to breathe without a ventilator.

“The hope and thought is that it’s going to change the lives of patients and their families,” said Stephanie Acord, M.D., a pediatric neurologist at Cook Children’s Jane and John Justin Neurosciences Center. “Without treatment, these kids and those who care for them are significantly affected. The earlier you treat SMA, the better.”

Dr. Acord directs the multi-disciplinary Muscular Dystrophy Association (MDA) Clinic at Cook Children’s Jane and John Justin Neurosciences Center where she and Warren Marks, M.D., medical director of movement disorders at the center, specialize in the treatment of SMA. Dr. Acord shared with us what every expectant parent needs to know about the disorder and the new screening.

What is SMA?

Spinal muscular atrophy is a genetic disorder in which the nerves within the brainstem and spinal cord, called alpha motor neurons, break down and lose the ability to send signals from the brain to the muscles. Without those signals, the muscles grow weak from lack of use and affect a baby’s ability to hold up and control their head, sit up, crawl, walk, swallow, speak and breathe. If left untreated, a child will eventually require a feeding tube and respiratory support, such as a ventilator. Untreated SMA is among the leading genetic causes of death of infants and children.

Spinal muscular atrophy can be passed to a child if both parents have a defective survival motor neuron (SMN1) gene. Parents do not have the disease or signs of the disease and do not usually know they carry an abnormal gene. The faulty gene inhibits the production of the protein that fuels these motor neurons and, without it, the nerves die. There is a back-up copy, the SMN2 gene, but it doesn’t work as well as the SMN1 gene.

It is estimated that about 100 children born in Texas each year have the disorder. Many newborns will not show signs of SMA for months. By that point, you’ve lost valuable treatment time and the ability to give a child with SMA a better life. This is why newborn screening is so important.

What are the signs and symptoms of SMA?

There are several types of SMA. Symptoms vary depending on the type, but muscle weakness and loss of muscle control that worsens over time are general indicators. It is important to note that SMA is not a cognitive disorder, but a muscular one.

Type 0 is the rarest and most severe form of the disorder. Babies born with Type 0 SMA have breathing problems very early on and typically do not survive.

Type 1 is the most common form of SMA and also considered severe. Infants will begin showing signs within six months of life. They have poor head control, do not sit independently and have difficulty sucking and swallowing. Even though cognitively they are normal, they are unable to speak due to weakness. Without treatment they will need assistance with breathing, feeding, communicating, sitting and walking.

Type 2 is a more moderate form of the disorder. Symptoms will become evident between six months to 18 months of life. Infants with Type 2 will have difficulty controlling their lower limbs. They may be able to sit independently and crawl but struggle with walking.

Type 3 is a milder form of SMA. Symptoms such as mild muscle weakness, difficulty walking or frequent respiratory illness do not appear until after 18 months of life. Some people may not experience symptoms until early adulthood.

Type 4 is adult onset SMA. It is rare, progresses slowly and typically doesn’t appear until the early 30s. Most people maintain mobility and are able to manage their symptoms without much interruption to their lives.

What treatment is available for SMA?

The Federal Drug Administration (FDA) approved the first treatment for SMA in December 2016.

“It used to be a diagnosis in which there was very little treatment and little hope,” Dr. Acord said. “But the treatment now available for these patients is completely different than it was just five years ago.”

Today, there are three FDA-approved treatments. Two—Spinraza® and Evrysdi®—are drug therapies that help stimulate the production of a more functional SMN2 protein. These two treatments require ongoing administration of medication at various time intervals. The other—Zolgensma®—is a gene-replacement therapy administered once through an IV that delivers a normal functioning copy of the SMN1 gene.

The treatments have varying degrees of success, but all work to improve the strength and function of muscles through healthier neurons. They help to prolong the amount of time a child can live without additional support such as equipment to help them breathe more comfortably, as well as increase their ability to speak with their voice and to eat to some extent by mouth. The most critical part of any of the treatments is to start as soon as possible following diagnosis.

How will my newborn be screened for SMA?

As of June 1, 2021, SMA is one of 55 disorders on Texas’ list of required newborn screenings. It does not require an additional test. It’s simply bundled into the routine screenings already performed on newborns via blood test.

What happens if my newborn is positive for SMA?

If your newborn’s screening is positive for SMA, it is recommended that they be referred to a specialist, either a pediatric neurologist or a pediatric neurogeneticist, within 24 hours. A specialist will most likely conduct additional testing to confirm the diagnosis and develop a treatment plan.

“Parents need to advocate getting their child to a specialist as quickly as possible,” Dr. Acord said about receiving a positive SMA screen.

Pediatric neurologists at Cook Children’s Medical Center are able to conduct many SMA assessments virtually via telemedicine, which is helping parents and children in parts of the state without specialists get access to care from the comfort of their home.

Click here to learn more about the Muscular Dystrophy Association Clinic at Cook Children’s and for contact information for clinic staff.

To help raise awareness of this rare genetic cause of neurodevelopmental disease, M. Scott Perry, M.D., medical director of neurology and director of the Genetic Epilepsy Clinic at Cook Children’s, shares basic information about the disorder and exciting advancements towards treatment for this rare disease.

What do SCN2A-related disorders look like? 

Children with genetic variants in SCN2A can develop early onset epilepsy with various levels of severity. SCN2A was first discovered as a cause of benign familial neonatal infantile seizures (BFNIS), a syndrome that often occurs in multiple family members. These children can develop seizures as newborns or infants, but can develop normally with good seizure control.

Later, SCN2A was discovered as a cause of infantile spasms and other early onset severe epilepsies of childhood, the so-called early infantile epileptic encephalopathies. The gene has also been linked to Ohtahara Syndrome, Dravet Syndrome, Migrating Partial Epilepsy of Infancy and West Syndrome amongst others. In addition, SCN2A variants are a major cause of intellectual disability, schizophrenia, and autism which may occur without associated epilepsy. A variety of other medical conditions may be present in people with SCN2A-related disorders, including sleep problems, cerebral palsy, and movement disorders to name a few.

What is the cause of SCN2A-related disorders? 

SCN2A is a gene which makes a sodium channel found primarily in the nerve cells that generate electricity. Two issues can occur with SCN2A. The first is a change in the gene which causes a gain of function – a change that allows too much sodium to enter the nerve cell and thus increases electricity – often presenting with epilepsy as a main symptom.

For others, SCN2A variants cause a loss of function – a change that decreases sodium entering the nerve cell and thus decreases electricity – more often presenting with autism and intellectual disabilities. Many mutations in SCN2A are de novo, meaning they occur spontaneously and were not inherited from the parents. This is often the case in more severe disease presentations. There are instances where SCN2A may be inherited from a parent and this is more commonly seen in benign presentations such as BFNIS.

How are SCN2A mutations diagnosed? 

Often, genetic testing can diagnose SCN2A mutations. The Behind The Seizure program provides free testing for children in the U.S. under the age of 8 years.

Magnetic resonance imaging (MRI) scans are often normal and electroencephalogram (EEG) findings may vary.

Is there a treatment for SCN2A-related disorders? 

While there is not yet a cure for SCN2A-related disorders, a significant amount of research is leading to exciting new therapies. Certain traditional sodium channel seizure drugs (for example, phenytoin, lamotrigine) have demonstrated more favorable responses for seizure control in select patients (often gain of function), while in others, sodium channel drugs may aggravate seizures.

New drugs are being developed that specifically target the abnormal channel produced by SCN2A. These treatments may provide more precise control of the channel without disrupting the function of other sodium channels like many traditional sodium channel seizure drugs. This may result in better seizure control with less side effects.

Potentially most exciting is the development of genetic approaches to therapy, treatments that don’t just treat symptoms, but aim to correct the genetic abnormality. Antisense oligonucleotides (ASO) are small pieces of genetic material that can be given to help increase or decrease production of SCN2A. This approach has been used in other genetic conditions (spinal muscular atrophy and Dravet syndrome) with success and represents a promising therapy for SCN2A disorders as well. This is just one of several genetic approaches to therapy on the horizon.

Where can you find more information about SCN2A disorders?

For more information about SCN2A and SCN2A Awareness Day, visit www.scn2a.org. The SCN2A Foundation serves as an excellent resource for information about SCN2A related disorders and helps connect a community of people living with these rare conditions. The site provides updates on SCN2A research as well.

Maybe you thought it was no big deal. Maybe you heard something about it that made you worry.

Here are 4 facts about sugar bugs that you should know:

1.Prominent veins are common in the newborn, infancy and childhood period. They can occur on the face, hands/feet, trunk and extremities (basically all over). If you look closely enough in all babies, you’ll find some veins that are more noticeable than others.

2.One suggested link with sugar bugs has been an association with mutations in a gene known as MTHFR. MTHFR mutations are common, approximately 50 percent of the population carries some type of mutation. The significance of MTHFR mutations is still unclear but no studies link the presence of sugar bugs to these mutations. You can read more about MTHFR mutations and there significance here: A Pediatrician Goes In-depth into MTHFR.

3.While it has been speculated by practitioners of traditional Chinese medicine that sugar bugs might suggest a syndrome (known as Kanmushi) where children show a voracious appetite and severe sensitivity to sugar, I find no evidence that support this is a true connection.

4.Proponents of Kanmushi suggest that you limit your child’s sugar intake, provide a structured environment and opportunities for physical activity. Obviously, these are great ideas for all children.

So, should you be worried about your child’s sugar bug?

It’s always possible that further information could surface, but given current theories and information, I would say that any connection to a more serious issue is unfounded and not a concern.

Learn more about Kanmushi by clicking here.