What is Spinal Muscular Atrophy?

Spinal Muscular Atrophy (SMA) is a neuromuscular disease that is passed on genetically to children by their parents.  It is a recessive genetic disease, meaning that BOTH parents must carry a copy of the abnormal gene and BOTH must pass this gene on to their child.  When both are carriers of this gene, there is a 25% chance in each pregnancy that the child will have SMA, a 50% chance that the child will be a carrier of the gene, and a 25% chance that the child will be completely unaffected.  SMA is a relatively common “ rare disorder” affecting 1 in 6,000 live births.   Approximately 1 in 35 people are genetic carriers.  SMA is the #1 genetic killer of children under 2 years of age.

An individual with SMA has a missing or mutated gene (SMN1, or Survival Motor Neuron 1) that produces a protein in the body called Survival Motor Neuron (SMN) protein.   This protein deficiency has the most severe affect on motor neurons.   Motor neurons are nerve cells in the spinal cord that send out nerve fibers through muscles throughout the body.  Since SMN protein is critical to the survival and health of motor neurons, without this protein nerve cells may atrophy, shrink, and eventually die, resulting in muscle weakness. 

As a child with SMA grows, their bodies are doubly stressed, first by the decrease in motor neurons and then by the increased demand on the nerve and muscle cells as their bodies grow larger.  The resulting muscle atrophy can cause weakness and bone and spinal deformities that may lead to further loss of function, as well as additional compromise of the respiratory (breathing) system. 

SMA mainly affects proximal muscles, which are those closest to the trunk of the body.  Weakness in the legs is generally greater than weakness in the arms.  Sensation and the ability to feel are NOT affected, and intellectual activity is normal.  It is often observed that patients with SMA are unusually bright and sociable.  The severity depends on what Type of SMA the child has.  There are 4 Types of SMA – Type 1, 2, 3, 4.  The determination of the Type of SMA is based upon the physical milestones achieved.  The earlier the symptoms are noticed, the more severe theType of SMA.  It is important to note that the course of the disease may be different for each child. 

SMA Type 1, also called Infantile SMA or Werdnig–Hoffmann Disease is the most severe form.  It is diagnosed before 6 months of age, but more often before 3 months of age.  Symptoms may even start in the womb.  Some mothers later recall the baby not moving as much in the last month or so of pregnancy.

Type 1 children are not able to hold up their heads, roll over, crawl, sit up without support, or walk.  All of their muscles are extremely weak, with the weakest muscles being the legs, upper arms, and neck.  There is a weakness of the intercostal muscles (the muscles between the ribs) that help expand the chest, and the chest is often smaller than usual.  The strongest breathing muscle is the diaphragm.  As a result, the individual appears to breathe with their stomach muscles.  The chest may appear concave (sunken in) due to the diaphragmatic (tummy) breathing. Also due to this type of breathing, the lungs may not fully develop, the cough is very weak, and it may be difficult to take deep enough breaths while sleeping to maintain normal oxygen and carbon dioxide levels.  SMA affects all muscle systems as well including sucking, swallowing, digesting food, and excretions.  Constipation is a common problem as is being able to control excessive drooling (secretions), and getting proper nutrition and calories for proper weight gain.   A common cold can easily turn into pneumonia which is what usually takes the lives of these children, along with respiratory failure or when they no longer have the lungs or chest muscles to be able to breathe on their own. 

Current statistics show that the average lifespan of a child with SMA Type 1, not put on permanent ventilation, is only 8 months of age, with 80% dying by the age of 1, and the majority of the rest dying by age 2.  However, each child is affected so differently by SMA, that they do not all follow the same path or progression.  Also, as more is learned about SMA, the lifespan of a Type 1 child can be lengthened depending on the severity of the symptoms for each individual child.  The line between each Type of SMA is not clearly defined, and it is common for a child to exhibit patterns of 2 types, thus confusing the issue of “life expectancy” for that child. 

SMA Type 2, also called Intermediate SMA, is diagnosed before 2 years of age, usually more like 15 months.  Many of these children learn to sit unsupported before any symptoms are noticed.  Weakness of the muscles in the legs and trunk develops and this makes it difficult for the child to crawl properly or to walk normally, if at all.  Weakness in the muscles in the arms occurs as well, but is not as severe as in the legs.  Feeding and swallowing problems are not common in Type 2 children, but are still possible.  The muscles of the chest wall are affected, causing poor breathing function.  Children with Type 2 SMA frequently have tongue fasciculations (tongue vibrating rapidly) and manifest a fine tremor in the outstretched fingers.  They have difficulty coughing and may have difficulty taking deep enough breaths while they sleep to maintain normal oxygen and carbon dioxide levels.  Scoliosis is almost uniformly present as these children grow, resulting in a need for spinal surgery or bracing at some point.  Decreased bone density can result in an increased susceptibility to fractures.  Physical growth continues at a normal pace and, most importantly, mental function is NOT affected.  The children are bright and alert and it is important that they receive all the available opportunities to develop their intellectual capacities to their fullest extent.  The long term outlook depends mainly on the severity of weakness of muscles of the chest wall and on the development of scoliosis.  Lifespan is always difficult to predict.  Mildly affected children may live into adulthood, while more severely affected children may die before or in their teens, due to pneumonia or other chest problems.  

SMA Type 3, also called Juvenile SMA or Kugelberg-Welander disease, is much more variable at age of onset.  Children can be diagnosed as early as 1 year old or as late as adolescence.  However, diagnosis prior to age 3 is typical.   SMA Type 3 is considerably milder than the infantile or intermediate form. With Type 3, a fine tremor can be seen in the outstretched fingers but tongue fasciculations are seldom seen.  Type 3 children are able to stand and walk, but usually have difficulty doing so.  Some can lose the ability to walk later in childhood, adolescence, or even adulthood, often due to growth spurts or illness.  They typically have a normal lifespan, but as weakness gets progressively worse, they usually become wheelchair bound. 

SMA Type 4, also called Adult Onset, begins around age 35.  It is very rare for Spinal Muscular Atrophy to begin between the ages of 18 and 30, and is much less common than the other forms.  It is typically characterized by a subtle onset and very slow progression.  The bulbar muscles, those muscles used for swallowing and respiratory function, are rarely affected in Type 4.  They usually have a normal lifespan, but weakness gets progressively worse, as in all forms of SMA.

TESTING

SMA is diagnosed through a blood test, which looks for the presence or absence of the SMN1 gene, in conjunction with a suggestive history and physical examination.  It cannot tell the type of SMA the individual has, and approximately 5% of individuals who do have SMA do not show the gene deletions.  However, for the 95% of individuals who do show the deletions, the diagnosis is 100% accurate, and the type of SMA can be determined by other physical factors. 

Occasionally, doctors may request a muscle biopsy or EMG (Electromyography) testing.  Since the genetic blood test became available, a muscle biopsy is almost never indicated and is valuable mainly in cases where the blood DNA test is negative. 

For more information about SMA, please visit the following links:

www.fsma.org
www.smasupport.org
www.our-sma-angels.com/ethan
www.DoctorBach.com
www.columbiasma.org
www.fightsma.org
www.smafoundation.org