1. Spinal Muscular Atrophy
It is a neuromuscular disease characterized by
degeneration of motor neurons resulting in
progressive muscular atrophy (wasting away) and
weakness. The clinical spectrum of SMA ranges
from early infant death to normal adult life with only
mild weakness. The most common form of SMA is
caused by mutation of the SMN gene. The SMN
gene is found on chromosome 5, the affected SMN
gene is called SMN1. This gene involves breaking
down and distributing protein, hence the muscle
weakness as lack of protein causes muscle
weakness and other problems

2. These patients often require comprehensive medical
care involving multiple disciplines, including
pediatric pulmonology, pediatric neurology,
pediatric orthopedic surgery, Lower Extremity &
Spinal Orthosis, pediatric critical care, and
physical medicine and rehabilitation; and physical
therapy, occupational therapy, respiratory therapy,
and clinical nutrition. Genetic counseling is also
helpful for the parents and family members.
Symptoms: The primary feature of SMA is muscle
weakness, accompanied by atrophy of muscle
contract. This is the result of denervation, or loss
of the signal to that is transmitted from the spinal
cord.

3. • This is normally transmitted from motor neurons
in the spinal cord to muscle via the motor neuron's
axon, but either the motor neuron with its axon, or
the axon itself, is lost in all forms of SMA. Many of
the symptoms of SMA relate to secondary
complications of muscle weakness, and as such
can be at least partially remediated by prospective
therapy.
• muscle weakness
• poor muscle tone

4. • weak cry
• weak cough
• limpness or a tendency to flop
• difficulty sucking or swallowing
• accumulation of secretions in the lungs or throat
• bell-shaped torso, caused by breathing using
muscles around the abdominal area
• clenched fists with sweaty hands
• flickering/vibrating of the tongue
• head often tilted to one side, even when lying
down
• legs that tend to be weaker than the arms

5. • legs lying in the "frogs leg" position
• hypotonia, areflexia, and multiple congenital
contractures (arthrogryposis) associated with loss
of anterior horn cells
• feeding difficulties
• increased susceptibility to respiratory tract
infections
• bowel/bladder weakness
• lower-than-normal weight
• developmental milestones, such as lifting the head
or sitting up, can't be reached

6. Diagnosis:
It can be made by the SMN gene test, which
determines whether there is at least one copy of
the SMN1 gene by looking for its unique
sequences in exons 7 and 8. In some cases, when
the SMN gene test is not possible or does not
show any abnormality, other tests such as an
EMG electromyography (EMG) or muscle biopsy
may be indicated.
. Genomic DNA was analyzed by MLPA,
conventional PCR-RFLP, and allele-specific PCR

8. Multiplex ligation-dependent probe
amplification (MLPA)
It is a variation of the PCR reaction that permits
multiple targets to be amplified with only a
single primer pair. Each probe consists of a two
oligonucleotide which recognize adjacent target
sites on the DNA. One probe oligonucleotide
contains the sequence recognized by the forward
primer, the other the sequence recognised by the
reverse primer. Only when both probe
oligonucleotides are hybridized to their respective
targets, they can be ligated into a complete probe.
The advantage of splitting the probe into two parts

9. is that only the ligated oligonucleotides, but not the
unbound probe oligonucleotides, are amplified. If
the probes were not split in this way, the primer
sequences at either end would cause the probes
to be amplified regardless of their hybridization to
the template DNA, and the amplification product
would not be dependent on the number of target
sites present in the sample DNA. . Each complete
probe has a unique length, so that its
resulting amplicons can be separated and
identified by (capillary) electrophoresis. This
avoids the resolution limitations of multiplex PCR.

10. The forward primer used for probe amplification
is fluorescently labeled, each amplicon generates
a fluorescent peak which can be detected by a
capillary sequencer. MLPA, is one of the only
accurate, time-efficient techniques to detect
genomic deletions and insertions (one or more
entire exons), which are frequent causes of
cancers such as hereditary non-polyposis
colorectal cancer (HNPCC), breast, and ovarian
cancer. MLPA can successfully and easily
determine the relative copy number of all exons
within a gene simultaneously with high sensitivity