NAME: MYMOON MUHAMMED HASHIM

GROUP: 404
DATE: 30/12/2020

THEME 14 : Neuromuscular diseases: muscular dystrophies,

spinal and neural amyotrophies. Myotonia. Myasthenia
gravis and myasthenia-like syndromes.
8.
What is proximal children's spinal muscular atrophy? What are
their clinical forms and how do they differ from each other?What
are the current treatment options?

ANS:
• Inherited by autosomal recessive type
• There are 3 phenotypic variants that differ in the age of clinical
manifestation, course and prognosis
• They are based on a single genetic mutation-deletion of 7-8
exons on chromosome 5q1, 3
• Type I or acute malignant infantile spinal amyotrophy Werding-
Hoffmann
• Type II or chronic infantile spinal amyotrophy (intermediate
type)
• Type III or Kugelberg-Velander juvenile spinal amyotrophy

Type I or acute malignant infantile spinal amyotrophy Werding-

Hoffmann
• Occurs with a frequency of 1:25000
• Debut from birth to 6 months
Leading symptoms:
• generalized weakness mainly in the proximal muscles
• hypotonia of the muscles in the supine position
• the frog pose with breeding and outerthe rotation of the hips
• tendon areflexia
 • Atrophy and fasciculations in the tongue, bulbar syndrome
• paradoxical breathing(weakness of the intercostal muscles,
and then of the diaphragm); deformity of the chest
• they can sit, but they can never walk
• If the debut is from birth, then the fatal outcome is at 6
months, if symptoms appear after 3 months-death at 2 years
due to intercurrent respiratory diseases
• Often combined with heart defects, microcephaly and
oligophrenia
• EMG: fibrillations and fasciculations potentials at rest and an
increase in the average amplitude of the MUP
• CFK concentration is normal

Type II or chronic infantile spinal amyotrophy (intermediate type)

• Starting at 6-24 months. The earlier it starts, the heavier the

current
• symmetrical proximal weakness, distal muscle areas suffer less
• inhibition of tendon reflexes
• patients can sit, many can stand, and rarely to walk
• facial and oculomotor muscles do not suffer in the early stages
• contractures are formed in childhood
• often there are pseudohypertrophy of the calf and glute
muscles
• feet gradually become equinovarus
• tremor of the hands, fasciculations in the tongue,
deformitiesspine and chest,congenital dislocation of the hip
joints
• On ENMG – potentials of fibrillary and fasciculate
• the progression of the disease is slow, patients live until
adulthood
Type III or Kugelberg-Velander juvenile spinal amyotrophy
• Frequency of 1.2:100000

• Debut between 2 and 15 years, more often in 5 years

Characteristically:

• Increasing weakness in the proximal parts of the legs, and then the
hands

• Sometimes pseudohypertrophy of the calf muscles

• Moderate weakness of the facial muscles

• Bone deformities ( approximately 50%), tendon retractions

• Tendon hypo - or areflexia

• Postural tremor of the hands

• The concentration of ck exceeds the norm by 2-4 times

• On EMG - spontaneous activity (fasciculations, fibrillations).When

muscle tension – increased amplitude , increased duration, and
decrease in the number of MUP

Treatment and prognosis of spinal amyotrophy

 There is no effective treatment. Treatment of all forms is
symptomatic
 Non-specific maintenance therapy: L carnitine, coenzyme
Q10, b vitamins
 Orthopedic care
 Physical rehabilitation
 Psychological support for the family
 Monitoring by palliative care services
 Spinraza (nusinersen) Biogen - it is an antisense
oligonucleotide for alternative splicing of the pre-mRNA of the
SMN2 gene, which is almost identical to SMN1, and therefore
the synthesis of the full-size SMN protein is enhanced
 Zolgensma (onasemnogen abeparvovek), Novartis – it is a
gene therapy treatment that, after a single dose, provides
replacement of the missing or defective SMN1 gene with its
functional copy. The result is a normal production of SMN
protein — and the corresponding healing of spinal muscular
atrophy
 Risdiplam - Is a modifier of splicing (genetic modification) of
the SMN2 gene, which increases the expression of full-size
functional proteins.Rosdiplom is orally administered, passes
the blood-brain barrier (BBB) and systematically affects the
Central and peripheral nervous system.