WHAT CAUSES SPINAL MUSCULAR ATROPHY?
SMA is an autosomal recessive genetic disease. In order for a child
to be affected by SMA, both parents must be carriers of the abnormal
gene and both must pass this gene on to their child. Although both
parents are carriers the likelihood of a child inheriting the disorder
is 25%, or 1 in 4.
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 its
most severe affect on motor neurons. Motor neurons are nerve cells in
the spinal cord which send out nerve fibers to 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 demands 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.
There are four types of SMA, SMA Type I, II, III, IV. The
determination of the type of SMA is based upon the physical milestones
achieved. It is important to note that the course of the disease may be
different for each child.
Type I SMA is also called Werdnig-Hoffmann Disease. The diagnosis of
children with this type is usually made before 6 months of age and in
the majority of cases the diagnosis is made before 3 months of age. Some
mothers even note decreased movement in of the final months of their
Usually a child with Type I is never able to lift his/her head or
accomplish the normal motor skills expected early on in infancy. They
generally have poor head control, and may not kick their legs as
vigorously as they should, or bear weight on their legs. They do not
achieve the ability to sit up unsupported. Swallowing and feeding may be
difficult and are usually affected at some point, and the child may show
some difficulties managing their own secretions. The tongue may show
atrophy, and rippling movements or fine tremors, also called
fasiculations. There is 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 in an SMA patient is
the diaphragm. As a result, the patient appears to breath 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.
The Diagnosis of Type II SMA is almost always made before 2 years of
age, with the majority of cases diagnosed by 15 months. Children with
this type may sit unsupported when placed in a seated position, although
they are often unable to come to a sitting position without assistance.
At some point they may be able to stand. This is accomplished with the
aid of assistance or bracing and/or a parapodium/standing frame.
Swallowing problems are not usually characteristic of Type II, but vary
from child to child. Some patients may have difficulty eating enough
food by mouth to maintain their weight and grow, and a feeding tube may
become necessary. Children with Type II SMA frequently have tongue
fasciculations and manifest a fine tremor in the outstretched fingers.
Children with Type II also have weak intercostals muscles and are
diaphragmatic breathers. They have difficulty coughing and may have
difficulty taking deep enough breaths while they sleep to maintain
normal oxygen levels and carbon dioxide levels. Scoliosis is almost
uniformly present as these children grow, resulting in need for spinal
surgery or bracing at some point in their clinical course. Decreased
bone density can result in an increased susceptibility to fractures.
The diagnosis of Type III, often referred to as Kugelberg-Welander or
Juvenile Spinal Muscular Atrophy, is much more variable in age of onset,
and children can present from around a year of age or even as late as
adolescence, although diagnosis prior to age 3 years is typical. The
patient with Type III can stand alone and walk, but may show difficulty
with walking at some point in their clinical course. Early motor
milestones are often normal. However, once they begin walking, they may
fall more frequently, have difficulty in getting up from sitting on the
floor or a bent over position, and may be unable to run. With Type III,
a fine tremor can be seen in the outstretched fingers but tongue
fasciculations are seldom seen. Feeding or swallowing difficulties in
childhood are very uncommon. Type III individuals can sometimes lose the
ability to walk later in childhood, adolescence, or even adulthood,
often in association with growth spurts or illness.
TYPE IV (ADULT ONSET)
In the adult form, symptoms typically begin after age 35. It is rare
for Spinal Muscular Atrophy to begin between the ages of 18 and 30.
Adult onset SMA is much less common than the other forms. It is defined
as onset of weakness after 18 years of age, and most cases reported as
type IV have occurred after age 35. It is typically characterized by
insidious onset and very slow progression. The bulbar muscles, those
muscles used for swallowing and respiratory function, are rarely
affected in Type IV.
Patients with SMA typically lose function over time. Loss of function
can occur rapidly in the context of a growth spurt or illness, or much
more gradually. The explanation for this loss is unclear based on recent
research. It has been observed that patients with SMA may often be very
stable in terms of their functional abilities for prolonged periods of
time, often years, although the almost universal tendency is for
continued loss of function as they age.