65. Neural and spinal muscular atrophy · Neurology · MU Plovdiv

Hereditary Motor and Sensory Neuropathy (Charcot-Marie-Tooth Disease). Spinal Muscular Atrophy

Clinically and heterogenous group of diseases affecting the peripheral nerves.
Characterised by progressive distal weakness and atrophy of muscles, distal sensory disorders, tendon hypo or areflexia.
More than 30 distinct forms

Hereditary disease; can be autosomal dominant, autosomal recessive or X dominant
Most common mutation is duplication of PMP22 gene on chromosome 17
Wide variety of pathogenetic mechanisms, each one driven by genetic defect
For example, duplication of PMP22 gene alters the collaboration between axons and Schwann cells.

Eight basic types of HMSN:

HMSN I (demyelinating type)
HMSN II (axonal type)
HMSN III (Dejerine-Sota syndrome, hypertrophic neuropathy, congenital hypomyelinating neuropathy)
HMSN IV (with excessive phytic acid, Refsum’s disease)
HMSN V (with spastic paraplegia)
HMSN VI (with optic atrophy)
HMSN VII (with pigmentary degeneration of the retina)
HMSN VIII (associated with other features)

Each of these basic types are subdivided into subtypes depending on the specificity of the clinical phenotypes and the underlying genetic defects.

Depending on type, onset can occur at any age but most often occurs in the 1st or 2nd decade
Gradually develop distal muscular weakness initially in lower and later in upper limbs
Tendon and superficial reflexes absent
Sensory disorders of distal type
Sensory ataxia
Distal trophic impairments with thinning of the shins, bilateral deformations of the feet, high instep (pes cavus)
Steppage gait characteristic feature
Kiphoscoliosis found in 15% of all HMSN cases
Roussy-Levi syndrome clinical variation of HMSN I characterised by postural tremor in upper limbs

Electrophysiological characteristics can differentiate the 3 most common HMSN types (I-III)
Conductance velocity in motor fibers of median nerve
HMSN I slow conductance below 38 m/sec
HMSN II conductance above 38 m/sec
HMSN III conductance much slower and is around 6 m/sec
Distal muscle wasting may be noted in the legs, resulting in the characteristic stork leg or inverted champagne bottle appearance.
Bony abnormalities: pes cavus, claw hand in ulnar nerve lesion.
Sensory ataxia so positive Romberg test
Vibration sensation and proprioception are significantly decreased, but patients usually have no sensory symptoms.
Spinal deformities (e.g. thoracic scoliosis)
Deep tendon reflexes are markedly diminished or are absent.
Vibration sensation and proprioception are significantly decreased, but patients usually have no sensory symptoms.
Sensation of pain and temperature is usually intact. Essential tremor is present