Spinal muscular atrophy (SMA

Question 1

Deff

Answer 1

4-10/100tys births
autosomal recessive motor neuron diseases that are caused by apoptosis of lower motor neurons.
typically present during infancy or early childhood with progressive weakness, hypotonia, muscle atrophy, hyporeflexia/areflexia, and varying degrees of bulbar weakness
defect in the SMN1 gene on chromosome 5q
defect in the assembly of small nuclear ribonucleoprotein (snRNP) to form the SMN complex → apoptosis of lower motor neurons (especially the anterior horn cells in the spinal cord)
Motor neurons of cranial nerves III, IV, and VI, and sacral motor neurons are not affected → preserved eye movement and continence

Question 2

Types 0-IV

Answer 2

0 type - prenatal - absent or decreased fetal movements, life expectancy <6mths
type 1 SMA (Werdnig-Hoffmann disease) ~ 55%
is associated with death within the first two years of life as a result of respiratory muscle paralysis or aspiration pneumonia
Severe muscle weakness (flaccid paralysis) and infantile hypotonia (frog-leg posture)
Symmetrical involvement of proximal muscles, mostly of the lower extremities
Intercostal muscle weakness → paradoxical breathing

Type 2 - 30% - intermediate severity, life expectancy. Up to 30 years/o [Fine hand tremors
Delayed motor milestones
Poor weight gain
Weak cough
Musculoskeletal abnormalities
Joint contractures
Hip dislocation
Kyphosis
Scoliosis]
Type 3 - mild
Type 4 - adult type - Variable degree of muscle weakness, Cramps, muscle aches

Question 3

Tx

Answer 3

nusinersen, which is highly effective in halting the progression of SMA1
–> induces differential splicing in the SMN2 gene (takes over SMN1)

SMN= human survival motor neuron protein

onasemnogene abeparvovec, a potentially curative genetic therapy - delivers a normal gene copy to the neurons

Question 4

Bulbar palsy

Answer 4

Severe bulbar palsy
Respiratory failure
Atrophy and fasciculations of the tongue
Fasciculations of the fingers
Weak cry and cough
Inability to swallow → difficulty feeding, drooling, ↑ risk of aspiration

Question 5

Dx

Answer 5

Genetic
EMG, muscle biopsy - atrophy of groups of motor units

Question 6

Diff dx

Answer 6

Congenital myasthenic syndromes: muscle weakness induced by fatigue, ptosis, extraocular muscle palsy
Congenital myopathies (prox mscls)
infections (polio, coxsackievirus, echovirus, West Nile virus) - acute onset
Hypotonic cerebral palsy : non-progressive weakness
Muscular dystrophies - increased CK
Rare juvenile form of amyotrophic lateral sclerosis
Progressive muscular atrophy - nonhereditary LMN disorder