OTHER DISORDER

Disorder name: Spinal Muscular AtrophyA decrease in the size and strength of a muscle
Acronym: SMA
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• What is SMA?
• What causes SMA?
• What are the symptoms and types of SMA?
• What treatments are available for SMA?
• What happens when SMA is treated?
• What caused the SMN protein to be absent or not working correctly?
• How is SMA inherited?
• Is genetic testing available for SMA?
• What other testing is available for SMA?
• Can you test for SMA during a future pregnancy?
• Can other members of the family be tested for SMA?
• How common is SMA?
• Does SMA happen more often in a specific ethnic group?
• Does SMA go by any other names?
• Where can I find more information and support?

This fact sheet contains general information about SMA. Every child is different and some of these facts may not apply to your child specifically. Certain treatments may be recommended for some children but not others. All children with SMA should be followed by a team of specialist doctors in addition to their primary doctor.

WHAT IS SMA?

Spinal Muscular Atrophy, also known as SMA, is an inheritedAcquiring a trait from one’s parents. Most traits, such as eye color or hair color, are inherited from a parent through genes. neurologic condition. SMA affects the motor neuronsA particular type of nerve cell that carries information from the brain to the muscles. in the spinal cord. Motor neurons are a type of specialized nerve cellThe smallest living unit. Cells make up all organs and tissues in multi-cellular organisms, like humans. They can also live independently, as in bacteria and other microorganisms. At a minimum, a cell is surrounded by a membrane, contains DNA at some stage in its life, and is able to replicate itself into two equal parts. that send signals from the brain to the muscles in the body. When motor neurons are not working correctly or are absent, they are unable to send these signals to the muscles correctly. Without the correct signals, the muscles have trouble working. Over time, the motor neurons get worse, causing muscles to start to weaken and atrophy (waste away). People with SMA can have a range of different symptoms starting at different ages. All individuals with SMA have problems with movement. In addition, they may have trouble eating and speaking and can have breathing problems, which can be severe. People with SMA have average intelligence and emotional development. SMA affects the muscles on both sides of the body and affects the proximal muscles, which are the muscles closest to the center of the body, such as the muscles of the shoulder, pelvis, upper arms, and legs.

WHAT CAUSES SMA?

SMA is an inherited condition caused by problems with a specific proteinA molecule that makes up many parts of every cell in the body. Examples of proteins include hormones, enzymes, hair, and antibodies. Proteins are made up of 20 different types of individual units called amino acids. It is the order of these amino acids in a protein that determines what form and function a protein has. Each gene holds the instructions for making a single protein. called survival motor neuron (SMN) protein. The SMN proteinSurvival motor neuron protein is a protein in the cells that helps build and maintain motor neurons. Motor neurons are special cells that help you move and control your muscles. When SMN protein is not working right, it causes muscle problems. plays a role in maintaining the motor neurons. When the SMN protein is damaged or missing, it does not work correctly, leading to the deterioration of the motor neurons over time. As this deterioration progresses, the motor neurons cannot talk to the muscles, which grow weaker and smaller.

WHAT ARE THE SYMPTONS AND TYPES OF SMA?

Symptoms of SMA include muscle weakness, difficulty moving, and breathing problems. Speech and feeding problems, scoliosisAn abnormal sideways curvature of the spine, and joint problems can develop. SMA is progressive, meaning nerve damage and symptoms worsen over time.

There are 5 subtypes of SMA, which can be classified based on the age of onset and the severity of symptoms. These separate types of SMA were more commonly used in the past, and it is now known that there is overlap between these types of SMA.

Type 0

SMA type 0 is the most severe form of SMA. Symptoms may begin before birth. Babies with SMA type 0 usually have severe weakness, poor muscle toneIn order to hold our posture and control our movements, a certain amount of tension is needed in our muscles. This tension is called “muscle tone.” People with hypotonia have too little tension in their muscles and appear “floppy.” People with hypertonia have too much tension in their muscles and have problems with tight, rigid muscles and joints., absent reflexesAn automatic and involuntary action of an organ or muscle in response to a stimulus. Examples of reflexes include the kick of the lower leg when the anterior knee is tapped and pupil constriction in response to bright light. Sometimes, certain expected reflexes do not happen automatically. This is called an absence of reflexes., and breathing problems at birth. They may also have heart issues and contracturesA tightening of muscle, tendons, or ligaments that prevents normal movement of the associated body part.  . Infants with Type 0 SMA often have very limited life expectancy, and many do not survive past infancy.

Type I

Babies with SMA type I develop symptoms between 0 and 6 months of age. They have significant muscle weakness, leading to difficulties in feeding, breathing, and problems with movement. Their muscle weakness affects their ability to move and they may not have head control or be able to sit without support. Historically, the life expectancy for children with Type 1 SMA was very limited, often only a couple of years.

Type II

Children with SMA type II develop symptoms between 6 to 18 months of age. They have muscle weakness, difficulty sitting up and rolling over, and absence of some reflexes. While they can stand, they are unable to walk independently. Children with Type 2 SMA can often live into adulthood, although they may require mobility aids such as walkers and may need treatments and therapies to help them breathe.

Type III

Individuals with SMA type III usually show symptoms after the age of 18 months. Symptoms begin with progressive muscle weakness and can cause fatigueFatigue is a feeling of weariness, tiredness, or lack of energy. Fatigue can be a normal and important response to physical exertion, emotional stress, or lack of sleep. However, it can also be a sign of a more serious health disorder. and difficulty walking stairs. Most individuals can walk independently when symptoms first start but may lose the ability to walk over time. Individuals with SMA type 3 have a near-normal lifespan and live into adulthood with appropriate medical care and support.

Type IVThis is a small tube placed into a vein, usually in the hand or arm. Medications and nutrients can be given through this tube directly into the blood. IV’s are often used in the hospital to give fluids, glucose and medication over a long period of time.

Individuals with SMA type IV have a later onset of symptoms – usually in adulthood. Individuals often have hand tremorsShaking or trembling movements in one or more parts of the body caused by problems with the nerves, fatigue, and progressive muscle weakness in the limbs. Individuals usually have an expected lifespan but may experience muscle weakness, causing unsteadiness while walking, falls, and other movement problems.

WHAT TREATMENTS ARE AVAILABLE FOR SMA?

While there is currently no cure for SMA, there are medications and treatments that can help manage and lessen symptoms and extend life expectancy.

For treatment to be most effective, it is important that it start at the right time. You may want to speak with your insurance, doctor, and family about the cost of treatments. Following up with doctors is critical as they help plan and adjust treatment for your child.

Medications

Nusinersen (Spinraza™) is a prescription medication that can be given to patients of all ages and is injected into the spine in a specialized treatment center. It requires multiple doses in the first year and maintenance doses 3 times a year. Nusinersen works by increasing the ability of the SMN2 gene to produce functional SMN protein. Having SMN protein that works correctly improves motor neuron function and the muscles’ functions.

Risdiplam (Evrysdi®) is a prescription medication taken by mouth once a day. The medication increases the ability of the SMN2 gene to produce functional SMN protein, which improves motor neuron function and the muscles’ function. Risdiplam can also be given through a feeding tube if needed.

Gene TherapyGene therapy – a type of treatment that transplants normal working genes into cells to replace non-working genes in order to treat genetic disorders. There are many ways that gene therapy can be done. Sometimes, a gene with a disease-causing variant can be replaced with a healthy gene. Sometimes, a gene with a disease-causing mutation can be inactivated or “silenced.” And sometimes, a new gene can be put into the body to help fight a disease. Some gene therapies are still experimental.

Onasemnogene abeparvovec (Zolgensma™) is a prescription gene replacement therapy that can be given to SMA patients under 2 years old. Zolgensma is administered as a one-time infusion into the bloodstream via an intravenous line (IV). From the bloodstream, Zolgensma goes to the motor neurons and delivers a working copy of the SMN1 gene to the motor neurons. This new SMN1 gene then produces a working SMN protein. As motor neurons receive the working SMN protein, they become healthier and more functional. This leads to improved muscle function and motor controlThe process of starting and using muscles for purposeful movement, reducing the severity of SMA symptoms and slowing down the progression of the disease.

Supportive Therapies

For people with SMA, supportive care is important to manage symptoms. Some patients receiving medication or gene therapy may still require ongoing supportive care and therapies to manage the breathing, feeding, and orthopedic problems caused by muscle weakness. You may be advised to see a doctor who specializes in caring for children with SMA or be seen at a specialized treatment center.  Specialists can work with your regular pediatrician to ensure up-to-date treatment for your child.

Neurology

A neurologistA specialist in the anatomy, functions, and organic disorders of nerves and the nervous system. cares for people with disorders of the nerves. They are often the primary doctor for people with SMA. They can help diagnose and monitor the progression of SMA. They can check nerve health and muscle strength and recommend treatments and therapies to help with complications.

Pulmonary Care

Pulmonologists specialize in lung care and breathing issues. Management with pulmonary care may include visits to the pulmonologistA doctor who specializes in lung conditions and breathing problems every 3-6 months, removal of mucus and airway clearance, assessment of quality of sleep, and measurement of oxygen levels in the blood.

Nutrition and Gastrointestinal Care

Gastroenterologists and nutritionists help to identify problems and make plans to ensure that nutritional needs are met. SMA can cause some people to struggle with eating and digestion. Constipation, undernutrition, and acid reflux are common symptoms.

Orthopedic and Musculoskeletal Care

Orthopedists help treat issues with the bone such as scoliosis and joint problems. Physical therapy can help people with SMA build muscle strength, increase mobility, and address challenges in daily life. Orthotic specialists help patients use frames, wheelchairs and other devices to improve movement and quality of life.

WHAT HAPPENS WHEN SMA IS TREATED?

Currently, no treatment reverses or completely stops the symptoms of SMA.  However, children who receive prompt and early treatment can live healthier and more productive lives. In patients with SMA, medication or gene therapy slows the progression of muscle weakness and improves survival. The goal of treatment is to lessen the health problems that occur with SMA and improve the quality of life of the person with SMA.

WHAT CAUSES THE SMA PROTEIN TO BE ABSENT OR NOT WORKING CORRECTLY?

GenesA segment of DNA that contains the instructions to make a specific protein (or part of a protein). Genes are contained on chromosomes. Chromosomes, and the genes on those chromosomes, are passed on from parent to child. Errors in the DNA that make up a gene are called variants and can lead to diseases. tell the body how to make proteins. The SMN1 gene instructs the body to make the SMN protein. Everyone has two copies of the SMN1 gene. People with SMA have changes, also called variantsA variant is a change or alteration in a person’s DNA sequence. Variants can happen in genes and affect how the gene functions. There are different types of variants – they can be non-problem causing (benign), disease-causing (pathogenic) or of unknown significance. The term variants is now used in place of the term mutation., in both copies of their SMN1 genes that cause them not to work correctly. Because of the variants in the SMN1 genes, the SMN protein either does not work correctly or is not made at all. This causes the problems seen in SMA. SMA is caused by variants in the SMN1 gene.

A second gene, called SMN2, is also involved in SMA. SMN2 does not cause SMA. SMN2 influences the severity of the symptoms of SMA.

HOW IS SMA INHERITED?

SMA is inherited in an autosomal recessiveMost of the metabolic disorders that can be detected by newborn screenings are inherited in an “autosomal recessive” pattern. Autosomal recessive conditions affect both boys and girls equally. How autosomal recessive inheritance works: Everyone has a pair of genes for each enzyme in the body. A separate pair of genes is responsible for making each enzyme. A person with a metabolic disorder has one enzyme that is either missing or not working properly. The problem is caused by a pair of “recessive” genes that are not working correctly. They do not make the needed enzyme. A person has to have two non-working “recessive” genes in order to have an autosomal recessive metabolic disorder. A person with an autosomal recessive disorder inherits one non-working gene from his or her mother and the other from his or her father. The parents are called carriers for that condition. Parents of children with a metabolic disorder rarely have the disorder themselves. Instead, for that pair of genes, each parent has one that is working correctly and one that is not working (called the “recessive” gene). People with a single non-working gene are called carriers. If one gene of the pair is working correctly, it makes up for the recessive non-working gene. Therefore, carriers usually will not have the condition. pattern. It affects both males and females equally.

Everyone has two copies of the SMN1 gene that makes the SMN protein. SMN protein is required for motor neurons to work. In individuals with SMA, both copies of their SMN1 gene are not working correctly. These individuals most often inherited one non-working SMN1 gene from each parent. A person with only one working copy of the SMN1 gene is called a carrier and does not show symptoms of SMA. One working copy of the SMN1 gene makes enough SMN protein for the body.

Parents of children with SMA typically do not have SMA. Two individuals who are carriersA person who has one copy of a gene mutation for a particular autosomal recessive disorder (remember genes come in pairs). Carriers are not affected by the disorder. However, they can pass on the gene variant to their children. Children who inherit two such gene variants will be affected by the disorder. The term variants is now used in place of the term mutation. have a chance to have a child together who could inherit two non-working copies of SMN1 and show symptoms of SMA.

When both parents are carriers of SMA, there is a 25% chance in each pregnancy for the child to have SMA. There is a 50% chance that the child will be a carrier of SMA. Like their parents, children who are carriers will not experience symptoms of SMA but have a chance of passing down their non-working copy of SMN1 to their children in the future. There is also a 25% chance that the child will not inherit any non-working copies of the SMN1 gene and will not have SMA.

Genetic counselingGenetic counseling gives patients and their families’ education and information about genetic-related conditions. It can help families make informed decisions. It is often provided by Genetic counselors or Medical geneticists who have special training in inherited disorders. is available to families who have children with SMA. Genetic counselorsThese are health care providers who have special training in genetic conditions. They help families understand genetic disorders and how they are passed down. Genetic counselors offer information and support to people who have genetic conditions in their families or are concerned that they may have a child with an inherited disorder. can answer questions about SMA, such as how the condition is inherited, choices during future pregnancies, and how to test other family members. You can ask your doctor about a referral to a geneticRelating to (or due to) genes and heredity or the field of studying genes and heredity. counselor.

IS GENETIC TESTING AVAILABLE?

Genetic testing for SMA can be done on a blood sample. Genetic testing, also called DNADeoxyribonucleic acid (DNA) is a molecule found in the chromosomes that carries genetic information. DNA is composed of four units (called bases) that are designated A, T, G, and C. The sequence of the bases spell out instructions for making all of the proteins needed by an organism. A gene is a section of DNA that holds the instructions for a specific protein. A change in one or more of the DNA bases making up a gene is called a mutation. Some mutations change the protein instructions and can lead to particular health problems or disorders. Each parent passes half of their chromosomes, and thus half of their DNA instructions, onto their children. It is these instructions that cause certain traits, such as eye or hair color, to be inherited. testing, looks for changes in both copies of the SMN1 genes.  In most children with SMA, both gene changes can be found. Rarely, in some children, neither or only one of the two gene changes can be found, even though we know they are present. Variants in SMN1 cause SMA.

Genetic testing of SMN2 is also done. SMN2 produces about 10% of the SMN protein in the body. People can have between 0 to 5 copies of SMN2. In general, people with SMA with a higher number of copies of SMN2 have milder symptoms of SMA. Determining the copy number of SMN2 can help doctors determine how severe the symptoms of SMA may be. SMN2 does not cause SMA, but it influences the severity of SMA.

WHAT OTHER TESTING IS AVAILABLE FOR SMA?

Newborn ScreeningA screening test that looks for different disorders using a small sample of blood taken from a newborn’s heel. A positive or abnormal newborn screening result means that there are slight differences that were found in the baby’s blood, and further testing is needed to figure out if the baby has a metabolic disorder.:

Most states test for SMA through newborn screeningThe process of testing for disease in a person who does not show signs of having the disease (nonsymptomatic or asymptomatic person). The goal of screening is to catch the disease in its early stages.. Newborn screening is a process where a few drops of blood are taken from a baby’s heel to identify different health conditions.

Newborn screening looks for SMA by checking for variants in a baby’s SMN1 genes. A positive newborn screen for SMA does not mean the baby has SMA. A positive screening test means that further testing must be done to confirm or rule out this condition. It is essential to follow up with your baby’s doctor, who will help coordinate care and testing for your baby.

Confirmatory/Diagnostic Testing:

After a positive result on the newborn screen, further diagnostic testing is done to confirm an SMA diagnosis. A positive screening result is confirmed using genetic testing. This genetic testing looks for variants in both copies of a baby’s SMN1 gene. SMN2 genes may be tested to help determine the severity and type of SMA.

Symptomatic testing

Older children or adults with late-onset SMA symptoms can have genetic testing to help diagnose if they have SMA. They can also have a neurologic exam to help clarify their symptoms. Other medical tests may include nerve conductions studies, electromyography and/or muscle biopsyThis is a procedure that involves taking a small piece of tissue (like skin) from a person to help diagnose a condition..

CAN YOU TEST FOR SMA DURING FUTURE PREGNANCY?

Genetic testing can be done during future pregnancies if the genetic changes causing SMA in a family are known. The DNA sample needed for this test is collected by either CVSThis is a special test done early in pregnancy. During CVS, a small sample of the placenta is removed for testing. This sample can be used to test for certain genetic disorders in the fetus. CVS is usually done between 10 and 12 weeks of pregnancy. or amniocentesisThis is a test done during pregnancy. A needle is used to remove a small sample of fluid from the sac around the fetus. The sample can be used to test for certain genetic disorders in the fetus. Amniocentesis to test for genetic conditions is usually done between 13 and 20 weeks of pregnancy.. 

Parents may choose to have SMA testing during a pregnancy or wait until after the birth. Parents may also choose to use assisted reproductive techniques to decrease the chance that their future children will have SMA. A genetic counselor can discuss your choices and answer questions about testing options before, during, or after pregnancy.

CAN OTHER MEMBERS OF THE FAMILY BE TESTED FOR SMA?

Having SMA

The younger brothers and sisters of a baby with SMA also have a chance of having SMA even if they have not yet shown symptoms. Finding out whether other children in the family have SMA is important because early treatment may prevent serious health problems. You should talk to your pediatrician and neurologist to arrange for testing of siblings if appropriate.

SMA Carrier testing

If two changes are found in the SMN1 gene in your child, other family members can have genetic testing to see if they are carriers of SMA.

Brothers and sisters who do not have SMA still have a chance to be carriers like their parents. Except in special cases, carrier testing should only be done on people over 18.

If you are a parent of a child with SMA, your brothers and sisters have a 50% chance to be a SMA carrier. It is important that other family members be told that they could be carriers. There is a small chance they are also at risk of having children with SMA.

All states offer newborn screening for SMA. However, when both parents are carriers, newborn screening results alone are insufficient to rule out SMA in a newborn baby. In this case, diagnostic testing should be done in addition to newborn screening.

HOW COMMON IS SMA?

Overall, SMA is thought to occur in approximately 1 out of every 6,000 -10,000 births in the United States.

SMA type 1 is the most common, followed by SMA type 3 and SMA type 2. SMA Type 4 is the mildest, and the birth prevalence is not well-defined, but it is thought to be less common than the earlier-onset types. SMA type 0 is the rarest form of SMA, and very few babies have been diagnosed with this type of SMA.

DOES SMA HAPPEN MORE OFTEN IN A SPECIFIC ETHNIC GROUP?

SMA affects people from all parts of the world. It occurs most commonly in Caucasians and Asians and less frequently in other ethnic groups. About 1 in 45 Caucasians are carriers of SMA, and about 1 in 48 Asians are carriers. SMA carrier frequencies range in other ethnic groups range from 1 in 55 to 1 in 100.

DOES SMA GO BY ANY OTHER NAMES?

SMA is also sometime called:

• 5q–linked spinal muscular atrophy
• 5q SMA
• Spinal amyotrophy

 Before the genetic cause of SMA were understood, the subtypes of SMA were known by other names.

• Type I was known as Werdnig-Hoffman disease and “acute SMA”
• Type II was known as Dubowitz disease and “chronicAny condition that lasts for a long period of time or occurs frequently. For example, diabetes and hemochromatosis are both chronic conditions. SMA”
• Type III was known as Kugelberg-Welander disease and “juvenile SMA”
• Type IV was known as “adolescent-onset” or “adult-onset SMA”

WHERE CAN I FIND MORE INFORMATION AND SUPPORT?

Medline Plus
https://medlineplus.gov/genetics/condition/spinal-muscular-atrophy/

CureSMA
https://www.curesma.org/

SMA Foundation
https://smafoundation.org/

National Institute of Neurological Disorders and StrokeThis is when the blood or oxygen supply to part of the brain is stopped. It can be caused either by a blood clot or a leak in a blood vessel. A stroke may cause loss of speech and language and the ability to move certain body parts. If severe, it can cause death.
https://www.ninds.nih.gov/health-information/disorders/spinal-muscular-atrophy

 

DOCUMENT INFO:

Created by:	www.newbornscreening.info
Reviewed by:	HI and OR Neurologist and GeneticistA person who specializes in genetics.
Review date:	December 8, 2023
Update on:	December 8, 2023

 

DISCLAIMER:

THIS INFORMATION DOES NOT PROVIDE MEDICAL ADVICE. All content (“Content”), including text, graphics, images and information are for general informational purposes only. You are encouraged to confer with your doctor or other health care professional with regard to information contained on this information sheet. After reading this information sheet, you are encouraged to review the information carefully with your doctor or other healthcare provider. The Content is not intended to be a substitute for professional medical advice, diagnosis or treatment. NEVER DISREGARD PROFESSIONAL MEDICAL ADVICE, OR DELAY IN SEEKING IT, BECAUSE OF SOMETHING YOU HAVE READ ON THIS INFORMATION SHEET. This project is supported by a grant from the MaternalHaving to do with the mother. and Child Health Bureau, Health Resources and Service Administration, Genetic Services Branch, MCH Project #:UH7MC30774-01-00 http://mchb.hrsa.gov