Article

Distal hereditary motor neuropathy (dHMN), also known as spinal
muscular atrophy, represents a group of clinically and genetically heterogeneous
diseases caused by degenerations of spinal motor neurons and leading to distal
muscle weakness and wasting. Nerve conduction studies reveal a pure motor
axonopathy and needle examination shows chronic denervation. STATE OF ART: dHMN
were initially subdivided into seven subtypes according to mode of inheritance,
age at onset, and clinical evolution. Recent studies have shown that these
subtypes are still heterogeneous at the molecular genetic level and novel
clinical and genetic entities have been characterized. To date, mutations in 11
different genes have been identified for autosomal-dominant, autosomal-recessive,
and X-linked recessive dHMN. Most of the genes encode protein involved in
housekeeping functions, endosomal trafficking, axonal transport, translation
synthesis, RNA processing, oxidative stress response and apoptosis. PERSPECTIVES:
The pathophysiological mechanisms underlying dHMN seem to be related to the
"length-dependent" death of motor neurons of the anterior horn of the spinal
cord, likely because their large axons have higher metabolic requirements for
maintenance. CONCLUSION: dHMN remain heterogeneous at the clinical and molecular
genetic level. The molecular pathomechanisms explaining why mutations in these
ubiquitously expressed housekeeping genes result in the selective involvement of
spinal motor neurons remain to be unravelled.
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Langue : FRANCAIS