2. Today’s discussion is on
Introduction
Aetiology
Mode of inheritance
Classification
Signs and symptoms
Diagnosis of spinal muscular atrophy
Treatment
Rehabilitation
Prognosis and
Researches
3. Introduction
• Spinal muscular atrophies (SMAs) are
Degenerative diseases of motor neurons
Begins in fetal life and
Continue to be progressive in infancy and childhood
• Motor neurons spared are
Cranial nerves III, IV, and VI to extra ocular muscles
Sacral spinal cord innervating urethra and anal sphincter muscles
Upper motor neurons.
4. • After cystic fibrosis (1:6,000), SMA is the next most fatal
disease with this genetic profile, with an incidence of 1:6,000
to 1:10,000 births.
• Second most common neuromuscular disease, following
Duchenne muscular dystrophy.
• The frequency of carriers (heterozygotes) is one in 40 to 60
people.
5. Aetiology
• Pathologic continuation of
Programmed cell death (apoptosis) of neuroblasts
Normal in embryonic life
• The survivor motor neuron gene (SMN)
Arrests apoptosis of motor neuroblasts
SMN mutation leads to persistence of apoptosis, even in later life.
6. • SMN is caused by
Homozygous mutation
Deletion of the SMN1 gene
Telomeric region of chromosome 5q13.
• Severity increases with
Involvement of number of copies of SMN2 gene
Similar to SMN1 gene
Centromeric region of chromosome 5q13.
7. • Genetic alteration to the SMN1 gene leads to
Reduction in survival motor neuron (SMN) protein.
SMN2 gene produces only 25% of SMN protein,
So it can’t compensate for SMN 1 gene.
• The lack of the SMN protein leads to
Degeneration of alpha (α) motor neurons
In the ventral horn of spinal cord.
8. Mode of Inheritance
• SMA disorders are inherited in an autosomal recessive manner.
• Autosomal recessive inheritance
Child must inherit a copy of the defective gene from both parents.
These parents are likely to be asymptomatic.
Often affects more than one person in the same generation.
• Kennedy’s disease, an adult form of SMA is X-linked inherited,
Sons will be affected and
Daughters will become carriers.
9. Classification
SMA in children is classified into four types based on
Ages of onset,
Severity and
Progression of symptoms.
10. All four types are caused by defects in the SMN1 gene.
SMA type 1 (Werdnig-Hoffmann disease or severe infantile form )
SMA type 2 ( late infantile or slow progressive form)
SMA type 3 (Kugelberg-Welander disease or chronic form)
SMA type 4 (Adult onset SMA)
Other forms of SMA include:
Type 0 form of SMA
Congenital SMA with arthrogryposis
Kennedy’s disease
11. Clinical features
• Progressive degeneration of lower motor neurons i.e.,
Nerve cells in the brain stem and spinal cord
• Which controls essential voluntary muscle activities like
Speaking,
Walking,
Breathing, and
Swallowing will be gradually lost
12. • When there are disruptions in the signals between LMNs and muscles
The muscles gradually weaken and may begin wasting away and
Develop uncontrollable twitching called fasciculation.
• When there are disruptions in the signals between UMNs and LMNs
The limb muscles develop stiffness called spasticity.
Movements become slow and effortful.
Knee and ankle jerks become overactive.
13. SMA type1
(Werdnig-Hoffmanndiseaseorinfantile-onsetSMA)
• Evident by the time a child is 6 months old presents with
Hypotonia (severely reduced muscle tone)
Diminished limb movements,
Lack of tendon reflexes,
Fasciculations, tremors, swallowing
Feeding difficulties and impaired breathing.
14. • Some children also develop scoliosis or other skeletal
abnormalities.
• Affected children never sit or stand and the vast majority
usually die of respiratory failure before the age of 2.
• However, the survival rate in individuals with SMA type I
has increased in recent years, in relation to the growing
trend toward more proactive clinical care.
15. SMA type II
(The Intermediateform)
• Usually begin between 6 and 18 months of age.
• Children may be
Able to sit without support
Unable to stand or walk unaided,
• Bulbar weakness combined with swallowing difficulties, can
lead to reduced weight gain in some children.
16. • Difficulties with coughing and with cleaning secretions from
the trachea
• Fine trembling (known as fasciculation)
• Can suffer from Scoliosis and contractures as they age.
• The progression of disease is variable.
• Life expectancy is around 10 to 40 years.
17. SMA type III
(Kugelberg-Welanderdisease)
• Appears between 2 and 17 years of age presents with
Abnormal gait,
Difficulty running,
Climbing steps or rising from a chair and
Fine tremor of the fingers.
• The lower extremities are most often affected.
18. • Complications include
Scoliosis and
Joint contractures
Chronic shortening of muscles or tendons around joints
Caused by abnormal muscle tone and weakness,
Which prevents the joints from moving freely.
• Individuals with SMA type III may be prone to respiratory
infections, but with care may have a normal lifespan.
19. Type IV
(Adult-onset SMA)
• Onset: 18-50 years.
• Symptoms and characteristics:
Generalised muscle weakness and wasting,
muscle twitches are common.
• Prognosis:
Symptoms remain relatively mild and has little impact.
20. • Inheritance
Autosomal recessive and dominant forms.
• In Type IV SMA, individuals should
Life expectancy can be improved with rehabilitation measures
21. Type 0 form
Present during perinatal period
Highly fatal
Motor neuron degeneration in the spinal cord
Starts as early as midgestation
22. Other forms
CongenitalSMA withArthrogryposis
• A rare disorder.
• Persistent contracture of joints with fixed abnormal posture of
the limb.
• Manifestations include
• Severe contractures,
• Scoliosis,
• Chest deformity,
• Respiratory problems,
• Unusually small jaws, and
• Drooping of the upper eyelids.
23. Kennedy’s disease
• Progressive spinobulbar muscular atrophy
• Onset: 15 and 60 years of age.
• Affected individuals may have
Enlargement of the male breasts or
Develop noninsulin-dependent diabetes mellitus.
24. • The onset of symptoms varies and includes
• Weakness and atrophy of the facial, jaw, and tongue muscles
• leading to problems with chewing, swallowing and speech.
• Early symptoms may include muscle pain and fatigue.
• Weakness in arm and leg muscles closest to the trunk with
• Muscle atrophy and fasciculations.
• Sensory loss in the feet and hands.
25. Diagnosis
• Molecular genetic tests
To identify deletions or mutations of the SMN1 gene.
This test identifies at least 95% of SMA Types I, II, and III.
• Electromyography to record the electrical activity
From the brain and spinal cord to a peripheral nerve root in
Arms and legs that controls muscles
During contraction and at rest.
26. • Nerve conduction velocity studies
Which measure electrical energy by
Assessing the nerve’s ability to send a signal.
• Muscle biopsy used to diagnose
Neuromuscular disorders and may also reveal if
A person is a carrier of a defective gene that could be passed on
to children.
• Laboratory tests of blood, urine, and other substances.
27. Treatment
Pharmacological
• There is no cure and treatment consists of managing the symptoms
and preventing complications.
• Muscle relaxants such as baclofen, tizanidine, and the
benzodiazepines may reduce spasticity.
• Botulinum toxin may be used to treat jaw spasms or drooling.
• Excessive saliva can be treated with amitriptyline, glycopyolate, and
atropine or by botulinum injections into the salivary glands.
• Antidepressants may be helpful in treating depression.
28. Rehabilitation
• Occupational and physiotherapy improves
Posture,
Prevent joint immobility
Slow muscle weakness and atrophy.
• Stretching and strengthening exercises reduces
Spasticity,
Increase range of motion and
Keeps circulation flowing.
• Some individuals requires additional therapy for
Speech,
Chewing and swallowing difficulties.
29. • Applying heat may relieve muscle pain.
• Assistive devices such as
Supports or braces,
Orthotics,
Speech synthesizers and
Wheelchairs may improve the quality of life with SMA.
30. Rehabilitation
• Proper nutrition and a balanced diet are essential to
maintaining weight and strength.
• People who cannot chew or swallow may require insertion of
a feeding tube.
• Non-invasive ventilation at night can prevent apnoea in sleep
• some individuals may also require assisted ventilation due to
muscle weakness in the neck, throat and chest during
daytime.
31. Prognosis
• Prognosis varies depending on the type of SMA.
• SMA type 1 & 2 and SMA type 0 are fatal.
• Kennedy’s disease
Course varies and slowly progressive.
Ambulatory until late in the disease.
Life expectancy for usually normal.
• People with SMA
Stable for long periods
Improvement should not be expected.
32. Researches
• Scientists are devoloping gene therapy
To halt motor neuron destruction and
Slow disease progression in mouse models of SMA.
• Scientists have found that
Anti-sense oligonucleotides
Can block or correct the processing of RNA molecules,
Which are the intermediates between genes and proteins.
• These compounds have shown therapeutic promise in animal models
