eMedicine Specialties > Neurology > Pediatric Neurology

Spinal Muscular Atrophy

Author: Bryan Tsao, MD, Associate Professor, Department of Neurology, Loma Linda
University; Chair and Service Chief, Department of Neurology, Loma Linda University
Medical Center
Coauthor(s): Carmel Armon, MD, MSc, MHS, Professor of Neurology, Tufts University
School of Medicine; Chief, Division of Neurology, Baystate Medical Center
Contributor Information and Disclosures

Updated: Jan 14, 2009

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• Overview
• Differential Diagnoses & Workup
• Treatment & Medication
• Follow-up

• References
• Keywords
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Introduction
Background

The spinal muscular atrophies (SMAs) comprise a group of autosomal-recessive disorders

characterized by progressive weakness of the lower motor neurons.

In the early 1980s, Werdnig and Hoffman described a disorder of progressive muscular
weakness beginning in infancy that resulted in early death, though the age of death was
variable. In pathologic terms, the disease was characterized by loss of anterior horn cells. The
central role of lower motor neuron degeneration was confirmed in subsequent pathologic
studies demonstrating a loss of anterior horn cells in the spinal cord and cranial nerve nuclei.1
Since then, several types of spinal muscular atrophies have been described based on age when
accompanying clinical features appear. The most common types are acute infantile (SMA
type I, or Werdnig-Hoffman disease), chronic infantile (SMA type II), chronic juvenile (SMA
type III or Kugelberg-Welander disease), and adult onset (SMA type IV) forms.

The genetic defects associated with SMA types I-III are localized on chromosome 5q11.2-
13.3.2,3,4,5

Many classification systems have been proposed and include variants based on inheritance,
clinical, and genetic criteria. Among these are the Emery6 , Pearn7 , and International SMA
Consortium system8 . The ISMAC system is most widely accepted and is used in this review.

Pathophysiology

In 1995, the spinal muscular atrophy disease-causing gene, termed the survival motor neuron
(SMN), was discovered.9 Each individual has 2 SMN genes, SMN1 and SMN2. More than 95%
of patients with spinal muscular atrophy have a homozygous disruption in the SMN1 gene on
chromosome 5q, caused by mutation, deletion, or rearrangement. However, all patients with
spinal muscular atrophy retain at least 1 copy of SMN2, which generates only 10% of the
amount of full-length SMN protein versus SMN1. This genomic organization provides a
therapeutic pathway to promote SMN2, existing in all patients, to function like the missing
SMN1 gene.10

Frequency

United States

The spinal muscular atrophies are the second most common autosomal-recessive inherited
disorders after cystic fibrosis. The acute infantile-onset SMA (type I) affects approximately 1
per 10,000 live births; the chronic forms (types II and III) affect 1 per 24,000 births. SMA
types I and III each account for about one fourth of cases, whereas SMA type II is the largest
group and accounts for one half of all cases.11

International

The incidence of spinal muscular atrophy is about 1 in 10,000 live births with a carrier
frequency of 1 in 50.7,12

Mortality/Morbidity

The mortality and/or morbidity rates of spinal muscular atrophy are inversely correlated with
the age at onset. High death rates are associated with early onset disease. In patients with
SMA type I, the median survival is 7 months, with a mortality rate of 95% by age 18 months.

• Respiratory infections account for most deaths.

• In type II SMA, the age of death varies, but death is most often due to respiratory
complications.
• See Prognosis for more information.

Sex
Male individuals are most frequently affected, especially with the early-onset forms of spinal
muscular atrophy, ie, types I and II.13

Age

The ISMAC classification system is based on the age of onset.8 See Background, History, and
Physical for a review of the existing classification systems and a brief discussion of their
relevancy to the role of age in spinal muscular atrophies.

According to the ISMAC system, the age of onset for spinal muscular atrophies is as follows:

• SMA type I (acute infantile or Werdnig Hoffman): Onset is from birth to 6 months.
• SMA type II (chronic infantile): Onset is between 6 and 18 months.
• SMA type III (chronic juvenile): Onset is after 18 months.
• SMA type IV (adult onset): Onset is in adulthood (mean onset, mid 30s).

Clinical
History

The diagnosis of spinal muscular atrophies includes the following a detailed clinical history.
Obtaining a complete family history facilitates genetic counseling.

Patients with spinal muscular atrophy present with weakness and muscle wasting in the limbs,
respiratory, and bulbar or brainstem muscles. They have no evidence of cerebral or other CNS
dysfunction. Patients with spinal muscular atrophy often have above-average intelligence
quotients (IQs) and demonstrate high degrees of intelligence.

The clinical manifestations of each particular form of spinal muscular atrophy are
discussed:14,2,15,16,17

• SMA type I - Acute infantile or Werdnig-Hoffman disease

o Patients present before 6 months of age, with 95% of patients having signs and
symptoms by 3 months. They have severe, progressive muscle weakness and
flaccid or reduced muscle tone (hypotonia). Bulbar dysfunction includes poor
suck ability, reduced swallowing, and respiratory failure. Patients have no
involvement of the extraocular muscles, and facial weakness is often minimal
or absent. They have no evidence of cerebral involvement, and infants appear
alert.
o Reports of impaired fetal movements are observed in 30% of cases, and 60%
of infants with SMA type I are floppy babies at birth. Prolonged cyanosis may
be noted at delivery. In some instances, the disease can cause fulminant
weakness in the first few days of life. Such severe weakness and early bulbar
dysfunction are associated with short life expectancy, with a mean survival of
5.9 months. In 95% of cases, infants die from complications of the disease by
18 months.
• SMA type II - Chronic infantile form
o This is the most common form of spinal muscular atrophy, and some experts
believe that SMA type II may overlap types I and III.
 o Most children present between the ages of 6 and 18 months.
o The most common manifestation that parents and physicians note is
developmental motor delay. Infants with SMA type II often have difficulties
with sitting independently or failure to stand by 1 year of age.
o An unusual feature of the disease is a postural tremor affecting the fingers.
This is thought to be related to fasciculations in the skeletal muscles.
o Pseudohypertrophy of the gastrocnemius muscle, musculoskeletal deformities,
and respiratory failure can occur.
o The lifespan of patients with SMA type II varies from 2 years to the third
decade of life. Respiratory infections account for most deaths.
• SMA type III - Chronic juvenile or Kugelberg-Welander syndrome
o This is a mild form of autosomal recessive spinal muscular atrophy that
appears after age 18 months.
o SMA type III is characterized by slowly progressive proximal weakness. Most
children with SMA III can stand and walk but have trouble with motor skills,
such as going up and down stairs.
o Bulbar dysfunction occurs late in the disease.
o Patients may show evidence of pseudohypertrophy, as in patients with SMA
type II.
o The disease progresses slowly, and the overall course is mild. Many patients
have normal life expectancies.
• SMA type IV - Adult-onset form
o Onset is typically in the mid 30s.
o In many ways, the disease mimics the symptoms of type III.
o Overall, the course of the disease is benign, and patients have a normal life
expectancy.

Physical

Patients with disease of the lower motor neurons present with flaccid weakness, hypotonia,
decreased or absent deep tendon reflexes, fasciculations, and muscle atrophy.

• SMA type I - Acute infantile or Werdnig-Hoffman disease

o Diffuse muscle weakness and hypotonia can be demonstrated with a variety of
bedside maneuvers, including the traction response, vertical suspension, and
horizontal suspension tests.
o In general, infants with SMA type I cannot hold their heads up when pulled to
the sitting position, and they will slip through the examiner's hands when held
vertically. They lay limp in the physician's hand when held under the abdomen
and facing down.
o Weakness is greater in proximal than distal muscles and may mimic muscle
disease (myopathy).
o Findings on sensory examination are normal. Deep tendon reflexes are absent,
as are long-tract signs and sphincteral abnormalities.
o Arthrogryposis, or deformities of the limbs and joints at birth, can be observed
and results from in utero hypotonia. Skeletal deformities (scoliosis) may be
present.
o In the infant or newborn, fasciculations are often restricted to the tongue, but
tongue fasciculations can be difficult to distinguish from normal random
movements unless atrophy is also present.
• SMA type II - Chronic infantile form
o Infants cannot get to a sitting position on their own, though they may stay
upright if placed in that position.
o As with SMA type I, SMA type II cause notable, symmetric proximal
weakness, hypotonia, and fasciculations.
o Findings on sensory examination are normal, and long-tract signs are absent.
When the patient's hands are held out, a characteristic fine postural tremor may
be observed.
• SMA type III - Chronic juvenile or Kugelberg-Welander syndrome
o Children can ambulate, but they have proximal muscle weakness and various
degrees of muscle hypotonia and wasting.
o The lower extremities are often more severely affected than the upper
extremities.
• SMA type IV - Adult-onset form: Patients are similar to those with SMA type III in
presentation and clinical findings, though the overall degree of motor weakness is less
severe in type IV than in type III.
• Spinal muscular atrophy variants
o Juvenile bulbar palsy, or bulbar hereditary motor neuronopathy (HMN) types I
and II: Bulbar HMN I (Vialletto-van Laere syndrome) is an autosomal
recessive syndrome that begins in the second decade of life. It is characterized
by facial weakness, dysphagia and dysarthria followed by facial weakness and
compromised respiratory function. The distinguishing feature of this syndrome
is the development of bilateral sensorineural hearing loss.
o Bulbar HMN II (Fazio-Londe disease): This is characterized by progressive
bulbar paralysis in the first decade of life. Patients present with stridor,
dysarthria, and dysphagia. Cranial-nerve involvement leads to facial diplegia,
ptosis, and ophthalmoplegia. Generalized weakness of the lower motor neurons
and rare corticospinal-tract signs are sometimes observed. Median survival for
patients with bulbar HMN II is 18 months.18
o Distal spinal muscular atrophy (spinal CMT or HMN type II): This may
clinically mimic Charcot-Marie-Tooth (CMT) disease, otherwise known as
hereditary motor and sensory neuropathy (HMSN) types 1 and 2: CMT is
characterized by peroneal muscular atrophy, weakness, and wasting in the legs.
High foot arches (pes cavus) are often present. Deep tendon reflexes are
reduced or absent. Distal large fiber sensory loss is found on examination,
although patients do not usually present with complaints of subjective sensory
loss. Compared with CMT, patients with distal spinal muscular atrophy do not
have sensory loss and the electrodiagnostic examination shows sparing of
sensory nerves.4
19
o X-lined recessive bulbospinal muscular atrophy (Kennedy disease): Patients
present with bulbar weakness, gynecomastia, and lower motor neuron
weakness beginning at age 20-40 years. Muscles cramps often precede
weakness, and facial and perioral fasciculations are seen in more than 90% of
patients. Increased rates of type 2 diabetes, infertility, and hand tremor are
associated with Kennedy disease. This condition results from a triple repeat
mutation (cytosine-adenine-guanine [CAG]) in exon 1 of the androgen receptor
gene on the X chromosome. Because of the X-linked nature of Kennedy
disease, daughters of affected patients are obligated carriers; therefore, genetic
counseling is indicated.
o Scapuloperoneal spinal muscular atrophy: Type 1 (AD form) appears at age
14-26, with weakness, distal leg atrophy, and absent tendon reflexes and
sparing of intrinsic foot muscles. Facial, bulbar, and pectoral muscles are
rarely affected. Progression is slow, with survival into the seventh or eight
decade of life.
o Type 2 (AR form): Patients present between birth and age 5 years, with
weakness and atrophy of the lower extremities and pectoral girdle. The course
is variable, and patients can survive to the fourth decade.20
o X-linked form scapuloperoneal spinal muscular atrophy: This has been
described with an onset before age 10 years. Patients present with weakness of
the pectoral girdle and arms with contractures. Cardiac conduction defects and
cardiomyopathy are noted. The syndrome is slowly progressive but stabilizes
by age 20 years, and patients survive to the sixth decade.
o Davidenkow syndrome: This is a form of scapuloperoneal SMA characterized
by weakness of the pectoral girdle and distal leg muscles, pes equinovarus, and
distal sensory loss and fasciculations. Autosomal dominant (age of onset, 15-
30 y) and autosomal recessive (age of onset, <15 y) forms have been
described. The clinical course is slow in the autosomal dominant form,
whereas the course of the autosomal recessive form is unknown.
o Fascioscapulohumeral (FSH) SMA: Most reports of this disorder are from
Japan. It is an autosomal dominant or sporadic disorder characterized by limb-
girdle and facial weakness occurring before age 20 years. The phenotype of
FSH SMA is similar to that of FSH dystrophy (FSHD), another unrelated
muscular dystrophy. However, FSH SMA does not have the chromosome 4
gene deletion seen in FSHD. Progression is slow, and the overall prognosis is
good.
o Scapulohumeral spinal muscular atrophy: Described initially in a Dutch
family, this autosomal dominant disorder is characterized by the onset of
scapulohumeral weakness and atrophy between the fourth and sixth decades of
life. Progression is rapid, with death from respiratory failure occurring within 3
years.
o Oculopharyngeal spinal muscular atrophy: This disorder is seen mainly in
people of French-Canadian descent and is characterized by bulbar and cranial-
nerve weakness followed by myopathic weakness of the limbs. The pattern of
inheritance is autosomal dominant with variable penetrance. The onset is
usually in the fourth to fifth decades of life, and the disease is slowly
progressive.
o Ryukyuan spinal muscular atrophy: This is an autosomal recessive disorder
described in men who live in the Japanese community on Ryukyu Islands. The
onset is before age 5 years, and the disease is characterized by weakness and
atrophy of the lower extremities, skeletal abnormalities (eg, scoliosis), and foot
deformities (eg, pes cavus). Deep tendon reflexes are diminished or absent.
The course of disease is unknown.21
o Other: Other variants have been described, including spinal muscular atrophy
with pontocerebellar hypoplasia (PCH), multiple long-bone fractures at birth,
diaphragmatic paralysis with early respiratory failure, congenital heart defects,
arthrogryposis, segmental amyotrophy, vocal-cord paralysis (distal HMN type
VII), and disease of the anterior horn cell with agenesis of the corpus
callosum.22,23,24,24
Causes

• In 1995, the SMN gene, responsible for SMA types I-III, was mapped to the long arm
of chromosome 5. (See Pathophysiology.)
o Two copies of the SMN gene have been identified on the 5q arm: a telomeric
SMN gene (SMNt, or SMN1) and a centromeric SMN gene (SMNc, or SMN2).
These 2 genes are nearly identical except for base-pair changes in exons 7 and
8. About 95% of all cases of SMA involve a homozygous deletion of the
SMN1 gene.25
o Expression of SMN1 produces the full-length SMN protein. In contrast,
expression of SMN2 produces a truncated version of the SMN protein that is
missing the 16 amino acids from the carboxy terminus. This truncated protein
results from a base-pair switch in exon 7 of the SMN2 gene. This switch leads
to alternative splicing of SMN2 mRNA, with removal of the exon 7 sequence.
About 70-80% of the gene product is in the form of this truncated protein.
Only about 10-25% of the protein produced is the full-length functioning
form.25
o Deletions or mutations in the SMN1 gene substantially decrease expression of
the SMN protein. Expression of SMN2 alone does not appear to produce
sufficient amounts of SMN protein to permit normal mRNA processing in the
lower motor neurons. Inefficient or abnormal mRNA processing appears to
have a toxic effect on the lower motor neurons and results in cellular
degeneration.26
o SMN protein is part of a multimeric protein complex that plays a critical role
in the assembly of snRNPs. These snRNPs are essential for early pre-mRNA
splicing. The hypothesis is that impaired or reduced formation of snRNPs
impairs mRNA splicing, with a toxic effect on normal cellular function. Why
this mutation results in such selective degeneration of lower motor neurons is
unclear, though the SMN protein is expressed in many types of neurons and
organ systems.27
• Neuronal apoptosis inhibitory protein (AIP), NAIP, gene
o This gene was also identified in 1995. Homozygous deletions of this gene are
found in 45% of patients with SMA type I and in 18% of patients with SMA
types II or III.
o This gene belongs to a class of highly conserved AIPs that help to regulate
programmed cell death. Deletion of this gene appears to be associated with
severe phenotypes of SMA.28
• BFT2p44 gene: Mutations in this gene have been found in 15% of patients with SMA

Primary Lateral Sclerosis

Other Problems to Be Considered

Acid maltase deficiency (type II glycogenosis)

Adrenoleukodystrophy
Botulism
Congenital hypomyelination neuropathy
Congenital polyneuritis
Down syndrome
GM1 gangliosidosis
Hurler syndrome
Infantile Gaucher disease
Marfan or Prader-Willi syndrome
Metabolic disorders (including the organic acidurias and mitochondrial diseases)
Neonatal and congenital myasthenia gravis
Peripheral neuritis
Poliomyelitis
Spinal cord transection
Type II (Pompe) glycogen storage disease

Workup
Laboratory Studies

• Laboratory testing
o The creatine kinase (CK) level is typically normal in SMA type I and normal
or slightly elevated in the other types.
o CSF findings are normal.
• Genetic testing
o Both prenatal and postnatal tests are now commercially available.
o Tests for chromosome arm 5q should be performed.
o The 1992 ISMAC found that the accuracy of prenatal prediction by means of
chorionic villi sampling and amniocentesis was 88-99%.
o Caution should be exercised when prenatal prediction is done in the presence
of atypical features (see SMA variants in Physical) because these clinical
variations may represent other pathogenic processes.

Other Tests

• Most cases spare the cardiac system, and ECGs are normal.
• Electrophysiologic studies are useful in differentiating the spinal muscular atrophies
from other neurogenic and myopathic diseases.30,31
o With the exception of Kennedy and Davidenkow syndromes, sensory nerve
conduction is normal in spinal muscular atrophy.
o Compound motor action potentials (CMAPs) are low normal or reduced,
depending on the severity of disease. In chronically weak muscles, CMAPs
may be in the near-normal because of reinnervation and collateral sprouting.
Motor velocities are normal. Modest slowing of motor conduction, when
present, may accompany severe motor axon loss because of the loss of the
fastest-conducting motor fibers.
• In affected muscles, needle-electrode examination reveals widespread broad and
polyphasic motor unit potentials (MUPs) firing in a reduced or rapid neurogenic
recruitment pattern.
o Superimposed low-amplitude, short-duration, and polyphasic MUPs may be
present. These configuration changes may resemble myopathic MUPs, but in
the case of spinal muscular atrophy are instead due to early MUP
reinnervation.
 o Fibrillation potentials may be seen in limb and paraspinal muscles and are
most striking in early or progressive spinal muscular atrophy. In late-juvenile
and adult-onset forms, active motor axon loss is sparse.
o Fasciculation potentials are uncommon, but spontaneously firing motor unit
action potentials (MUAPs) at 5-15 Hz have been described as a unique feature
of SMA I and II.
• Mild pseudomyotonic discharges have been observed in patients older than 6 years.
However, these discharges are not specific for etiology and may be seen in chronic
neurogenic disorders.

Procedures

• Muscle biopsy may necessary to differentiate spinal muscular atrophies from other
neuromuscular disorders if genetic analysis is unrevealing. Muscle selection should be
centered on clinically affected muscles but not to such a degree that degeneration
renders the tissue unrecognizable.
• Adequate results can be obtained with open or needle biopsy as long as the physician
has adequate experience in the procedure and in processing of the tissue.
• Electron microscopy can be used to evaluate for storage diseases.

Histologic Findings

Histologic findings depend on the stage and progression of disease. Initial changes include
atrophy of muscle fibers with compensatory hypertrophy. This results in groups of large and
small fibers (fiber-type grouping).

During the first 6-8 weeks of life, differentiating congenital fiber type disproportion and SMA
may be difficult. In the chronic forms of SMA, secondary myopathic changes may be seen in
addition to type grouping and may histologically resemble the muscular dystrophies.32,33

Classic histologic findings include the following:

• Degeneration and loss of spinal motor neurons with a neurogenic pattern of muscle
morphology
• Occasional neuronal chromatolysis with loss of myelinated axons in both anterior and
posterior roots
• A disproportionate loss of myelin in the thoracic and lumbar segments (especially in
the corticospinal tracts) with relative sparing of the cervical cord
• Motor neurons in the brainstem, notably in the hypoglossal nucleus. (Reactive gliosis
and secondary degeneration in roots and nerves are seen. However, these findings are
not necessarily pathognomic for the SMAs.)

Treatment
Medical Care

The first report of in vivo activation of SMN2 by valproic acid in 2006 led to a clinical study
of 7 patients with genetically-confirmed SMA type III/IV.34,35 The results of the clinical trial
are summarized as follows:
 • This was an open-label retrospective trial with examiners blinded to prior strength
testing. Patient age ranged from 17-45 years with a mean age of 33 years.
• Duration of treatment was 8 months at a dose of valproic acid 250 mg twice a day,
which was then increased to 500 mg twice a day after 3 months, as tolerated.
• Treated patients were found to have a mean increase in quantitative muscle strength of
16% compared with normal strength and 48% compared with pretreatment
values. Functional benefit was present in 6 of 7 patients; only 1 did not experience any
improvement.
• Follow-up at 1 year showed sustained benefit. The onset of improvement was
surprisingly quick, reported within a few months in most with initiation of valproic
acid.
• Common adverse effects included initial sedation and an average weight gain of 5 lb.
• Larger controlled studies are underway.

Supportive treatment should be aimed at improving the patients' quality of life and
minimizing disability, particularly in patients with slow progression.

• The treatment of patients with adult-onset spinal muscular atrophy is similar to that for
amyotrophic lateral sclerosis (ALS), except that the course and life span in spinal
muscular atrophies is considerably longer.
o A multidisciplinary approach is essential and encompasses physical,
occupational, speech, and respiratory therapies.
o The use of splints, bracing, and spinal orthoses can be customized to each
patient.36
o The goals are to maximize the patient's independence and quality of life at
each stage of the disease.
o Specific pharmacologic therapy is not available.
o Gene-specific therapy is not yet available.
• Patients and families can also be directed to ongoing clinical trials for the treatment of
spinal muscular atrophies. Descriptions of various trials can be found at the following
Web sites:
o National Institutes of Health
o Families of Spinal Muscular Atrophy
o Spinal Muscular Atrophy Foundation

Surgical Care

• Surgical revision may provide stable correction of the spine, and early orthopedic
intervention may be indicated in patients in whom prolonged survival is anticipated.
• Noninvasive ventilation and percutaneous gastrostomy reportedly improves the quality
of life with no effect on survival. These modalities may be most effective in
prolonging lifespan in patients with slowly progressive disease, whereas they may
provide comfort care in rapidly progressive infantile forms.37

Consultations

Consultations for ancillary evaluations and treatments are appropriate. Consult the following
specialists as needed: physical therapist, occupational therapist, speech therapist, dietary or
nutritional therapist, social service staff, pulmonologist, and gastroenterologist.
Diet

Ensuring optimal caloric intake enables patients to use weak muscles to their maximum
capacity without incurring obesity as a comorbid condition.

Activity

• Encourage mobility. The goal of active but nonfatiguing exercises is to maintain range
of motion, increase muscle flexibility, and prevent contractures. These exercises
should not produce pain or exhaustion.
• Preventing spinal deformities (eg, scoliosis) and joint contractures is important. This
goal is accomplished by using range-of-motion exercises, knee-ankle-foot orthoses,
specialized wheelchairs and seats at home and school, and home assistance devices.

Follow-up
Deterrence/Prevention

• Genetic counseling should be offered to all families of patients with spinal muscular
atrophy. Obtaining a complete family history facilitates genetic counseling.
• Education on how the disease is inherited may avert conception of affected
individuals.
• Furthermore, the role of prenatal diagnosis, particularly in pregnant carriers or those
with juvenile or adult-onset forms, should also be addressed.

Complications

Medical complications associated with the SMAs include pulmonary infections, spinal
deformities (eg, scoliosis), joint contractures, and respiratory failure.

Prognosis

See Mortality/Morbidity for more information.

• Most patients with SMA type I die before 18 months of age. In contrast, outcomes of
juvenile and adult spinal muscular atrophies are difficult to define because the
progression of these diseases varies widely.
• Survival probabilities for types I and II and probabilities of being ambulatory for type
III were derived for 445 patients. These patients were subdivided on the basis of
ISMAC criteria (ie, developmental milestones and age of onset).38
o SMA I: Survival probabilities at ages 2, 4, 10, and 20 years were 32%, 18%,
8%, and 0%, respectively.
o SMA II: Survival probabilities at ages 2, 4, 10, and 20 years were 100%,
100%, 98%, and 77%, respectively.
o SMA III: Results differed.

Onset before age 3 years: Probabilities of being ambulatory at ages 2,
4, 10, 20, and 40 years were 98%, 94.5%, 73%, 44%, and 34%,
respectively.

Onset after age 3 years: Probabilities of being ambulatory at ages 2, 4,
10, 20, and 40 years were 100%, 100%, 97%, 89%, and 67%,
respectively.
• The life expectancy of patients with SMA type III is close to that of the healthy
population. Antibiotic treatment has not prolonged survival in SMA type I. Birnkrant
examined the role of noninvasive positive-pressure ventilation and gastrostomy in
patients with SMA type I. Although these supportive measures can be effective in
slowly progressive neuromuscular diseases, they did not alter survival in patients with
SMA type I.37

Patient Education

Normal schooling in patients with SMA, especially types II and II or more indolent forms, is
highly recommended because their intelligence is normal or even superior to that of other
individuals.

Miscellaneous
Medicolegal Pitfalls

• As weakness and disability progress, patients with spinal muscular atrophy may reach
a point when it is unsafe for them to operate a motor vehicle or other machinery that
requires dexterity.
• The risk of falling may increase.
• In addition to advising patients about the matters listed above, the physician should
instruct them to comply with state regulations and to apply common sense.
• A decision should be made about how patients wish to be treated when they develop
ventilatory failure, preferably well before it occurs.
o Advance directives are in order for adults.
o Early discussions regarding end-of-life issues with parents of affected children
and adolescents are highly recommended.

Special Concerns

• Other diseases and disease processes can mimic spinal muscular atrophy.
• In Walton's 1957 series of 107 floppy infants, spinal muscular atrophies accounted for
62% of cases, followed by the congenital myopathies (17%), which represented
numerous unrelated disease processes that were histochemically distinct. Atonic
cerebral palsy accounted for 14% (most with intellectual impairment), followed by
congenital muscular dystrophy (3%). Polymyositis, myasthenia gravis, and scurvy
represented the remaining cases.
• The terms benign maturation delay and dissociated motor development describe the
floppy infant with delayed motor milestones but preserved fine motor development
and speech without evidence of a muscular disorder. A spectrum of disorders
characterized by abnormal muscle maturation has been termed syndrome of congenital
fiber type disproportion. Afflicted infants are usually developmentally delayed.
• Other differential diagnoses in the infantile- and childhood-onset forms include the
following:
o Adrenoleukodystrophy
 o Congenital hypomyelination neuropathy
o Congenital polyneuritis
o Down syndrome
o Infantile botulism
o Marfan or Prader-Willi syndrome
o Metabolic disorders (including the organic acidurias and mitochondrial
diseases)
o Neonatal and congenital myasthenia gravis
o Peripheral neuritis
o Poliomyelitis
o Spinal-cord transection
• Degeneration of the motor neurons as a part of generalized storage diseases is rare, but
it has been observed in the following conditions:
o Acid maltase deficiency (type II glycogenosis)
o GM1 gangliosidosis
o Hurler syndrome
o Infantile Gaucher disease
o Type II (Pompe) glycogen storage disease
• A poliomyelitislike illness associated with acute asthma in childhood (asthmatic
amyotrophy, Hopkins syndrome) has been described.39
• Juvenile ALS with an autosomal recessive inheritance pattern can occur with a rapidly
progressive flaccid paralysis of all 4 limbs, but patients later develop pyramidal signs.
• Bulbar palsy in familial ALS and hereditary progressive bulbar palsy may mimic
adult-onset spinal muscular atrophies. In both cases, bulbar dysfunction may be the
initial manifestation, though patients with ALS invariably develop limb and
respiratory weakness in a short time.
• Alexander disease may cause bulbar paresis. The diagnosis is made by means of
electromyelography (EMG), head imaging studies, and appropriate biochemical
testing.
• The adult spinal muscular atrophy forms (especially early in the disease course) can be
difficult to distinguish from familial motor neuron disease (FMND). However,
FMND, by definition, eventually affect both the upper and lower motor neuron
systems, leading to pyramidal-tract signs and rapid progression.